DGIdb - AKT1 Gene Record

AKT1 207 Druggable GenomeClinically Actionable

Alternate Names:

207
AKT SERINE/THREONINE KINASE 1
AKT1
AKT
CWS6
PKB
PKB-ALPHA
PRKBA
RAC
RAC-ALPHA
164730
391
ENSG00000142208
OTTHUMG00000170795
Proto-oncogene c-Akt
PKB alpha
RAC-PK-alpha
Protein kinase B alpha
Protein kinase B
RAC-alpha serine/threonine-protein kinase
2
P31749
AKT1_HUMAN
PA24684
v-akt murine thymoma viral oncogene homolog 1
1479
NP_001014431
NM_001014431
RAC-ALPHA SERINE/THREONINE-PROTEIN KINASE (EC 2.7.1.37) (RAC-PK-ALPHA) (PROTEIN KINASE B) (PKB) (C-AKT). [SOURCE:UNIPROT/SWISSPROT;ACC:P31749]
TTDC00132
C-AKT
SERINE/THREONINE PROTEIN KINASE PKB
RAC-ALPHA SERINE/THREONINE KINASE
BE0000428
T67619

Gene Info:

Is VIP	false
Has Variant Annotation	true
Source Reported Gene Name	AKT1
GuideToPharmacology Gene Category Name	Akt (Protein kinase B)
GuideToPharmacology Gene Category ID	285
GuideToPharmacology Gene Type	enzyme
Human Readable Name	DRUGGABLE GENOME
CancerCommons Reported Gene Name	AKT
Target Class	Enzymes
Target Subclass	EC:2.7.11.1
Human Readable Name	SERINE THREONINE KINASE
Uniprot Status	Swiss-Prot
Human Readable Name	KINASE
Interpro Name	Serine/threonine- / dual-specificity protein kinase, catalytic domain
Interpro Short Name	Ser/Thr_dual-sp_kinase_dom
Interpro Type	Domain
Uniprot Evidence	1: Evidence at protein level
Interpro Acc	IPR002290
Gene Biotype	PROTEIN_CODING

(27 More Sources)

Gene Categories: Category Details

TRANSPORTER
TUMOR SUPPRESSOR
KINASE
SERINE THREONINE KINASE
PROTEASE
DRUGGABLE GENOME
CLINICALLY ACTIONABLE
ENZYME
TRANSCRIPTION FACTOR

Publications:

Saura et al., 2017, A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors., Cancer Discov
Blake JF et al., 2012, Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors., J Med Chem
Jang SW et al., 2007, Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death., Proc Natl Acad Sci U S A
Lassen et al., 2014, Effects of AKT inhibitor therapy in response and resistance to BRAF inhibition in melanoma., Mol. Cancer
Dumble et al., 2014, Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor., PLoS ONE
Pachl et al., 2013, Characterization of a chemical affinity probe targeting Akt kinases., J. Proteome Res.
Gungor et al., 2015, Dose-Finding Quantitative 18F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies., J. Nucl. Med.
Gimenez-Xavier P et al., 2018, Deep analysis of acquired resistance to FGFR1 inhibitor identifies MET and AKT activation and an expansion of <i>AKT1</i> mutant cells., Oncotarget
Lee D et al., 2017, AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells., Onco Targets Ther
Vivanco et al., 2014, A kinase-independent function of AKT promotes cancer cell survival., Elife
Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov
Sayles LC et al., 2019, Genome-Informed Targeted Therapy for Osteosarcoma., Cancer Discov
Xing Y et al., 2019, Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation., Breast Cancer Res
Kajno E et al., 2015, Development of a new model system to dissect isoform specific Akt signalling in adipocytes., Biochem J
Kammasud et al., 2009, 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases., Bioorg. Med. Chem. Lett.
Xu JL et al., 2012, Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict platinum-based chemotherapy response of advanced non-small cell lung cancers in a Chinese population., Asian Pac J Cancer Prev
Sasano et al., 2015, Preclinical Efficacy for AKT Targeting in Clear Cell Carcinoma of the Ovary., Mol. Cancer Res.
Ikeda M et al., 2008, Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia., Pharmacogenomics
Ai Y et al., 2015, Synthesis of CDDO-amino acid-nitric oxide donor trihybrids as potential antitumor agents against both drug-sensitive and drug-resistant colon cancer., J Med Chem
Mavrakis et al., 2008, Tumorigenic activity and therapeutic inhibition of Rheb GTPase., Genes Dev.
Venkatesan et al., 2010, Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor., J. Med. Chem.
Karelia N et al., 2010, Selenium-containing analogs of SAHA induce cytotoxicity in lung cancer cells., Bioorg Med Chem Lett
Schmid P et al., 2020, Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial., J Clin Oncol
Myers et al., 2016, Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology Group study., Gynecol. Oncol.
Shi H et al., 2014, Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy., Cancer Discov
Weller et al., 2017, Durable Control of Metastatic AKT1-Mutant WHO Grade 1 Meningothelial Meningioma by the AKT Inhibitor, AZD5363., J. Natl. Cancer Inst.
Hyman et al., 2017, AKT Inhibition in Solid Tumors With AKT1 Mutations., J. Clin. Oncol.
Davies et al., 2015, Tumors with AKT1E17K Mutations Are Rational Targets for Single Agent or Combination Therapy with AKT Inhibitors., Mol. Cancer Ther.
Tamura et al., 2016, Safety and tolerability of AZD5363 in Japanese patients with advanced solid tumors., Cancer Chemother. Pharmacol.
2019, Capivasertib Active against <i>AKT1</i>-Mutated Cancers., Cancer Discov
Gris-Oliver A et al., 2020, Genetic Alterations in the PI3K/AKT Pathway and Baseline AKT Activity Define AKT Inhibitor Sensitivity in Breast Cancer Patient-derived Xenografts., Clin Cancer Res
Chang MT et al., 2018, Accelerating Discovery of Functional Mutant Alleles in Cancer., Cancer Discov
Smyth LM et al., 2020, Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with <i>AKT1</i> <sup>E17K</sup>-Mutant, ER-Positive Metastatic Breast Cancer., Clin Cancer Res
Middleton G et al., 2020, The National Lung Matrix Trial of personalized therapy in lung cancer., Nature
Garrett et al., 2011, Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT., Invest New Drugs
Kastrinsky DB et al., 2015, Reengineered tricyclic anti-cancer agents., Bioorg Med Chem
Fiorino F et al., 2011, Synthesis of 1-naphtylpiperazine derivatives as serotoninergic ligands and their evaluation as antiproliferative agents., Eur J Med Chem
Le et al., 2016, Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer., Cancer Discov
Itoh T et al., 2008, Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells., Bioorg Med Chem
Chen HW et al., 2011, Inhibition of TNF-α-Induced Inflammation by andrographolide via down-regulation of the PI3K/Akt signaling pathway., J Nat Prod
Kim EJ et al., 2010, OGA inhibition by GlcNAc-selenazoline., Bioorg Med Chem
Kaneko R et al., 2007, Survivin down-regulation plays a crucial role in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor-induced apoptosis in cancer., J Biol Chem
Allen et al., 2013, Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects., Sci Transl Med
Tirosh et al., 1999, Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation., J. Biol. Chem.
Shome D et al., 2008, Ulcerative keratitis in gastrointestinal stromal tumor patients treated with perifosine., Ophthalmology
Hilberg et al., 2008, BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy., Cancer Res.
Leoni C et al., 2019, First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma., Am J Med Genet A
Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE
Okuzumi T et al., 2009, Inhibitor hijacking of Akt activation., Nat Chem Biol
Won et al., 2006, Small molecule-based reversible reprogramming of cellular lifespan., Nat. Chem. Biol.
Hudkins RL et al., 2012, Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent., J Med Chem
Hechtman et al., 2015, AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants., Mol. Cancer Res.
Rodina A et al., 2007, Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer., Nat Chem Biol
Su JL et al., 2007, Forkhead proteins are critical for bone morphogenetic protein-2 regulation and anti-tumor activity of resveratrol., J Biol Chem
Hsieh TC et al., 2014, Biochemical and cellular evidence demonstrating AKT-1 as a binding partner for resveratrol targeting protein NQO2., PLoS One
Charoenrungruang S et al., 2014, Gigantol, a bibenzyl from Dendrobium draconis, inhibits the migratory behavior of non-small cell lung cancer cells., J Nat Prod
Samadi AK et al., 2010, Withaferin A, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma., J Nat Prod
Hayes TK et al., 2019, A Functional Landscape of Resistance to MEK1/2 and CDK4/6 Inhibition in NRAS-Mutant Melanoma., Cancer Res
Barve V et al., 2006, Synthesis, molecular characterization, and biological activity of novel synthetic derivatives of chromen-4-one in human cancer cells., J Med Chem
Van Meter et al., 2006, Cotreatment with a novel phosphoinositide analogue inhibitor and carmustine enhances chemotherapeutic efficacy by attenuating AKT activity in gliomas., Cancer

IPATASERTIB AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Approval Status Phase II

Response Type predicted – sensitive

Indication/Tumor Type triple-receptor negative breast cancer

Publications:

Saura et al., 2017, A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors., Cancer Discov

Blake JF et al., 2012, Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors., J Med Chem

UPROSERTIB AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Specific Action of the Ligand Inhibition

Publications:

Lassen et al., 2014, Effects of AKT inhibitor therapy in response and resistance to BRAF inhibition in melanoma., Mol. Cancer

Dumble et al., 2014, Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor., PLoS ONE

Pachl et al., 2013, Characterization of a chemical affinity probe targeting Akt kinases., J. Proteome Res.

GSK-690693 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:

Lee D et al., 2017, AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells., Onco Targets Ther

MK-2206 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

allosteric modulator

inhibitory allosteric modulator (inhibitory)

Interaction Info:

Notes

combination therapy MK2206 + Vemurafenib

Indication/Tumor Type melanoma

Publications:

Vivanco et al., 2014, A kinase-independent function of AKT promotes cancer cell survival., Elife

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

Sayles LC et al., 2019, Genome-Informed Targeted Therapy for Osteosarcoma., Cancer Discov

CAPIVASERTIB AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type ovarian cancer

Evidence Type Actionable

Approval Status Phase I

Publications:

Weller et al., 2017, Durable Control of Metastatic AKT1-Mutant WHO Grade 1 Meningothelial Meningioma by the AKT Inhibitor, AZD5363., J. Natl. Cancer Inst.

Hyman et al., 2017, AKT Inhibition in Solid Tumors With AKT1 Mutations., J. Clin. Oncol.

Davies et al., 2015, Tumors with AKT1E17K Mutations Are Rational Targets for Single Agent or Combination Therapy with AKT Inhibitors., Mol. Cancer Ther.

PERIFOSINE AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name perifosine, KRX-0401

Novel drug target Novel Target

Indication/Tumor Type ovarian clear cell carcinoma

Publications:

Sasano et al., 2015, Preclinical Efficacy for AKT Targeting in Clear Cell Carcinoma of the Ovary., Mol. Cancer Res.

Shome D et al., 2008, Ulcerative keratitis in gastrointestinal stromal tumor patients treated with perifosine., Ophthalmology

MIRANSERTIB AKT1

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:

Leoni C et al., 2019, First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma., Am J Med Genet A

Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE

A-443654 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:

Okuzumi T et al., 2009, Inhibitor hijacking of Akt activation., Nat Chem Biol
AFURESERTIB AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Specific Action of the Ligand Inhibition

Publications:
chembl:CHEMBL379218 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:
XL-418 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Novel drug target Novel Target

Publications:
AZD-5363 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Publications:
BAY-1125976 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Publications:
EVEROLIMUS AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Phase Ib/II

Response Type sensitive

Publications:
MSC-2363318A AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Publications:
LY-2780301 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Publications:
MK-2201 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Publications:
SR-13668 AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Publications:
TRICIRIBINE PHOSPHATE AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Publications:

RESVERATROL AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:

Su JL et al., 2007, Forkhead proteins are critical for bone morphogenetic protein-2 regulation and anti-tumor activity of resveratrol., J Biol Chem

Hsieh TC et al., 2014, Biochemical and cellular evidence demonstrating AKT-1 as a binding partner for resveratrol targeting protein NQO2., PLoS One

CENISERTIB AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Publications:
OMIPALISIB AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:
NELFINAVIR AKT1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Publications:

CISPLATIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cisplatin + Perifosine

Indication/Tumor Type ovarian clear cell carcinoma

Response Type predicted – sensitive

Publications:

Xu JL et al., 2012, Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict platinum-based chemotherapy response of advanced non-small cell lung cancers in a Chinese population., Asian Pac J Cancer Prev

Sasano et al., 2015, Preclinical Efficacy for AKT Targeting in Clear Cell Carcinoma of the Ovary., Mol. Cancer Res.

Lee D et al., 2017, AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells., Onco Targets Ther

SIROLIMUS AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type predicted – sensitive

combination therapy Doxorubicin + Sirolimus

Evidence Type Actionable

Publications:

Mavrakis et al., 2008, Tumorigenic activity and therapeutic inhibition of Rheb GTPase., Genes Dev.
PACLITAXEL AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ipatasertib + Paclitaxel

Indication/Tumor Type triple-receptor negative breast cancer

Response Type predicted – sensitive

Publications:

Schmid P et al., 2020, Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial., J Clin Oncol

TEMSIROLIMUS AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Phase II

Response Type predicted – sensitive

Publications:

Myers et al., 2016, Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology Group study., Gynecol. Oncol.

VEMURAFENIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy MK2206 + Vemurafenib

Evidence Type Actionable

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

TRICIRIBINE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Phase I

Response Type no benefit

Publications:

Garrett et al., 2011, Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT., Invest New Drugs

PICTILISIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type resistant

Publications:

Le et al., 2016, Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer., Cancer Discov
DOXORUBICIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lymphoma

Response Type decreased response

Approval Status Preclinical - Cell line xenograft

Publications:

Mavrakis et al., 2008, Tumorigenic activity and therapeutic inhibition of Rheb GTPase., Genes Dev.
ONC-201 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type predicted – sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Allen et al., 2013, Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects., Sci Transl Med

CETUXIMAB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Irinotecan

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Hechtman et al., 2015, AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants., Mol. Cancer Res.

IRINOTECAN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Irinotecan

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Hechtman et al., 2015, AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants., Mol. Cancer Res.

ALPELISIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type breast cancer

Response Type resistant

Approval Status Preclinical - Cell culture

Publications:

Le et al., 2016, Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer., Cancer Discov
FLUOROURACIL AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

Publications:

Lee D et al., 2017, AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells., Onco Targets Ther
PALBOCICLIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type predicted - resistant

Publications:

Hayes TK et al., 2019, A Functional Landscape of Resistance to MEK1/2 and CDK4/6 Inhibition in NRAS-Mutant Melanoma., Cancer Res
TRAMETINIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type predicted - resistant

Publications:

Hayes TK et al., 2019, A Functional Landscape of Resistance to MEK1/2 and CDK4/6 Inhibition in NRAS-Mutant Melanoma., Cancer Res
FULVESTRANT AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Capivasertib + Fulvestrant

Indication/Tumor Type Her2-receptor negative breast cancer

Response Type sensitive

Publications:

Gris-Oliver A et al., 2020, Genetic Alterations in the PI3K/AKT Pathway and Baseline AKT Activity Define AKT Inhibitor Sensitivity in Breast Cancer Patient-derived Xenografts., Clin Cancer Res
SORAFENIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cisplatin + Gemcitabine + Sorafenib

Indication/Tumor Type invasive bladder transitional cell carcinoma

Response Type predicted – resistant

Publications:
GEMCITABINE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cisplatin + Gemcitabine + Sorafenib

Indication/Tumor Type invasive bladder transitional cell carcinoma

Response Type predicted – resistant

Publications:
ARCHEXIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Novel drug target Novel Target

Trial Name RX-0201 ,Archexin

combination therapy Everolimus + RX-0201

Publications:
APITOLISIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type endometrial cancer

Response Type sensitive

Approval Status Phase II

Publications:
GAMBOGIC AMIDE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Jang SW et al., 2007, Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death., Proc Natl Acad Sci U S A
chembl:CHEMBL480356 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kammasud et al., 2009, 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases., Bioorg. Med. Chem. Lett.
RISPERIDONE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ikeda M et al., 2008, Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia., Pharmacogenomics
BARDOXOLONE METHYL AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ai Y et al., 2015, Synthesis of CDDO-amino acid-nitric oxide donor trihybrids as potential antitumor agents against both drug-sensitive and drug-resistant colon cancer., J Med Chem

GEDATOLISIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Venkatesan et al., 2010, Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor., J. Med. Chem.

chembl:CHEMBL1086397 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Karelia N et al., 2010, Selenium-containing analogs of SAHA induce cytotoxicity in lung cancer cells., Bioorg Med Chem Lett
DABRAFENIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Shi H et al., 2014, Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy., Cancer Discov
TRIFLUOPERAZINE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kastrinsky DB et al., 2015, Reengineered tricyclic anti-cancer agents., Bioorg Med Chem
TOPOTECAN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Fiorino F et al., 2011, Synthesis of 1-naphtylpiperazine derivatives as serotoninergic ligands and their evaluation as antiproliferative agents., Eur J Med Chem
EUPALININ A AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Itoh T et al., 2008, Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells., Bioorg Med Chem
ANDROGRAPHOLIDE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Chen HW et al., 2011, Inhibition of TNF-α-Induced Inflammation by andrographolide via down-regulation of the PI3K/Akt signaling pathway., J Nat Prod
chembl:CHEMBL257158 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kim EJ et al., 2010, OGA inhibition by GlcNAc-selenazoline., Bioorg Med Chem
LOVASTATIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kaneko R et al., 2007, Survivin down-regulation plays a crucial role in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor-induced apoptosis in cancer., J Biol Chem

WORTMANNIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Tirosh et al., 1999, Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation., J. Biol. Chem.

CARBOPLATIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Xu JL et al., 2012, Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict platinum-based chemotherapy response of advanced non-small cell lung cancers in a Chinese population., Asian Pac J Cancer Prev

NINTEDANIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Hilberg et al., 2008, BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy., Cancer Res.
LY-294002 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Won et al., 2006, Small molecule-based reversible reprogramming of cellular lifespan., Nat. Chem. Biol.

CEP-11981 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Hudkins RL et al., 2012, Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent., J Med Chem

chembl:CHEMBL258844 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Rodina A et al., 2007, Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer., Nat Chem Biol
GIGANTOL AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Charoenrungruang S et al., 2014, Gigantol, a bibenzyl from Dendrobium draconis, inhibits the migratory behavior of non-small cell lung cancer cells., J Nat Prod
WITHAFERIN A AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Samadi AK et al., 2010, Withaferin A, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma., J Nat Prod
GENISTEIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Barve V et al., 2006, Synthesis, molecular characterization, and biological activity of novel synthetic derivatives of chromen-4-one in human cancer cells., J Med Chem
ADENOSINE TRIPHOSPHATE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Van Meter et al., 2006, Cotreatment with a novel phosphoinositide analogue inhibitor and carmustine enhances chemotherapeutic efficacy by attenuating AKT activity in gliomas., Cancer
chembl:CHEMBL188434 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
SOTRASTAURIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CANERTINIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL225519 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CI-1040 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
FASUDIL AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CMX-2043 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
STAUROSPORINONE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
MYRIOCIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
ENZASTAURIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL401930 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL28324 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
BMS-754807 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
5-METHOXYCANTHINONE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
LACTOQUINOMYCIN AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CANTHIN-6-ONE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL228654 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
SELUMETINIB AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CYC-116 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
GSK-269962A AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
LAUROGUADINE AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
RO-316233 AKT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ensembl: ENSG00000142208
- Version: 101_38
Alternate Names:

AKT1 Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
TdgClinicalTrial: P31749
- Version: January-2014
Alternate Names:

AKT1 Gene Symbol

Gene Info:

Target Class Enzymes

Target Subclass EC:2.7.11.1

Publications:

RussLampel: ENSG00000142208

Version: 26-July-2011

Alternate Names:

RAC-ALPHA SERINE/THREONINE-PROTEIN KINASE (EC 2.7.1.37) (RAC-PK-ALPHA) (PROTEIN KINASE B) (PKB) (C-AKT). [SOURCE:UNIPROT/SWISSPROT;ACC:P31749] Description

ENSG00000142208 Ensembl Gene Id

AKT1 Display Id

Gene Info:

Human Readable Name DRUGGABLE GENOME

Gene Categories:

DRUGGABLE GENOME

Publications:

HopkinsGroom: P31749
- Version: 11-September-2012
Alternate Names:

P31749 Uniprot Accession

RAC-ALPHA SERINE/THREONINE-PROTEIN KINASE Uniprot Protein Name

207 Entrez Gene Id

Gene Info:

Uniprot Status Swiss-Prot

Human Readable Name KINASE

Interpro Name Serine/threonine- / dual-specificity protein kinase, catalytic domain

Gene Categories:

KINASE, DRUGGABLE GENOME

Publications:
GuideToPharmacologyGenes: 1479
- Version: 4-March-2015
Alternate Names:

v-akt murine thymoma viral oncogene homolog 1 HUGO Gene Name

391 HUGO Gene ID

AKT1 Gene Symbol

Gene Info:

GuideToPharmacology Gene Category Name Akt (Protein kinase B)

GuideToPharmacology Gene Category ID 285

GuideToPharmacology Gene Type enzyme

Gene Categories:

SERINE THREONINE KINASE, KINASE

Publications:
CancerCommons: AKT1
- Version: 25-July-2013
Alternate Names:

207 Entrez Gene ID

Gene Info:

CancerCommons Reported Gene Name AKT

Publications:

PharmGKB: AKT1

Version: 18-August-2020

Alternate Names:

PA24684 PharmGKB ID

Gene Info:

Publications:

Ikeda M et al., 2008, Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia., Pharmacogenomics

Xu JL et al., 2012, Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict platinum-based chemotherapy response of advanced non-small cell lung cancers in a Chinese population., Asian Pac J Cancer Prev

JAX-CKB: AKT1

Version: 15-September-2020

Alternate Names:

207 CKB Entrez Id

AKT1 CKB Gene Synonym

AKT CKB Gene Synonym

Gene Info:

Publications:

Politz et al., 2017, BAY 1125976, a selective allosteric AKT1/2 inhibitor, exhibits high efficacy on AKT signaling-dependent tumor growth in mouse models., Int. J. Cancer

Schneeweiss A et al., 2019, Phase 1 Dose Escalation Study of the Allosteric AKT Inhibitor BAY 1125976 in Advanced Solid Cancer-Lack of Association between Activating AKT Mutation and AKT Inhibition-Derived Efficacy., Cancers (Basel)

Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE

DrugBank: BE0000428

Version: 5.1.7

Alternate Names:

AKT1 DrugBank Gene Name

P31749 UniProt Accession

207 Entrez Gene Id

Gene Info:

Publications:

Tsou et al., 2005, Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase., Toxicol. Appl. Pharmacol.

Ivanov et al., 2005, Combined treatment with EGFR inhibitors and arsenite upregulated apoptosis in human EGFR-positive melanomas: a role of suppression of the PI3K-AKT pathway., Oncogene

Wang et al., 2005, The role of Akt on arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation., Cell Res.

NCI: AKT1

Version: 14-September-2017

Alternate Names:

Gene Info:

Publications:

Tirosh et al., 1999, Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation., J. Biol. Chem.

DTC: AKT1

Version: 02-September-2020

Alternate Names:

Gene Info:

Publications:

Jang SW et al., 2007, Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death., Proc Natl Acad Sci U S A

Venkatesan et al., 2010, Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor., J. Med. Chem.

Karelia N et al., 2010, Selenium-containing analogs of SAHA induce cytotoxicity in lung cancer cells., Bioorg Med Chem Lett

HingoraniCasas: ENSG00000142208
- Version: 31-May-2017
Alternate Names:

ENSG00000142208 Gene Symbol

AKT1 Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

Publications:
MyCancerGenome: AKT1
- Version: 20-Jun-2017
Alternate Names:

207 Entrez Gene Id

AKT1 MyCancerGenome Gene Symbol

AKT MyCancerGenome Reported Gene Name

Gene Info:

Publications:
TALC: AKT
- Version: 12-May-2016
Alternate Names:

AKT Gene Symbol

Gene Info:

Publications:
ChemblInteractions: PKB
- Version: chembl_23
Alternate Names:

RAC GENE_SYMBOL

AKT1 GENE_SYMBOL

RAC-alpha serine/threonine-protein kinase UNIPROT

Gene Info:

Publications:
GuideToPharmacologyInteractions: ENSG00000142208
- Version: 20-July-2020
Alternate Names:

AKT serine/threonine kinase 1 GuideToPharmacology Name

P31749 UniProtKB ID

Gene Info:

Publications:
OncoKB: AKT1
- Version: 23-July-2020
Alternate Names:

207 OncoKB Entrez Id

PRKBA OncoKB Gene Synonym

RAC OncoKB Gene Synonym

Gene Info:

Publications:
TTD: RAC-alpha serine/threonine-protein kinase
- Version: 2020.06.01
Alternate Names:

AKT1 TTD Gene Abbreviation

T67619 TTD Target ID

Gene Info:

Publications:
HumanProteinAtlas: AKT1
- Version: 19.3
Alternate Names:

ENSG00000142208 Ensembl Gene ID

AKT Human Protein Atlas Gene Synonym

PKB Human Protein Atlas Gene Synonym

Gene Info:

Gene Categories:

ENZYME

Publications:
Pharos: AKT1
- Version: 03-September-2020
Alternate Names:

RAC-alpha serine/threonine-protein kinase Gene Name

P31749 UniProt ID

Gene Info:

Gene Categories:

KINASE, TRANSCRIPTION FACTOR, TRANSPORTER

Publications:
GO: AKT1
- Version: 05-September-2020
Alternate Names:

PKB GO Gene Synonym

RAC GO Gene Synonym

Gene Info:

Gene Categories:

SERINE THREONINE KINASE, KINASE

Publications:
Tempus: AKT1
- Version: 11-November-2018
Alternate Names:

AKT1 Gene Symbol

Gene Info:

Publications:
dGene: AKT1
- Version: 27-Jun-2013
Alternate Names:

207 Gene ID

AKT dGene Synonym

PKB dGene Synonym

Gene Info:

Gene Categories:

SERINE THREONINE KINASE, KINASE

Publications:
MskImpact: AKT1
- Version: May-2015
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
MyCancerGenomeClinicalTrial: AKT1
- Version: 30-February-2014
Alternate Names:

Gene Info:

Publications:
ClearityFoundationClinicalTrial: AKT1
- Version: 15-June-2013
Alternate Names:

Gene Info:

Publications:
ClearityFoundationBiomarkers: AKT1
- Version: 26-July-2013
Alternate Names:

Gene Info:

Publications:
FoundationOneGenes: AKT1
- Version: 03-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
CarisMolecularIntelligence: AKT1
- Version: 04-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
Oncomine: AKT1
- Version: v3
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
CGI: AKT1
- Version: 14-September-2020
Alternate Names:

Gene Info:

Publications:

Approval Status	Phase II
Response Type	predicted – sensitive
Indication/Tumor Type	triple-receptor negative breast cancer

Direct Interaction	yes
Mechanism of Interaction	Serine/threonine-protein kinase AKT inhibitor
Specific Action of the Ligand	Inhibition

Specific Action of the Ligand	Inhibition
Endogenous Drug?	False
Direct Interaction?	True

Notes
combination therapy	MK2206 + Vemurafenib
Indication/Tumor Type	melanoma

Indication/Tumor Type	ovarian cancer
Evidence Type	Actionable
Approval Status	Phase I

Trial Name	perifosine, KRX-0401
Novel drug target	Novel Target
Indication/Tumor Type	ovarian clear cell carcinoma

combination therapy	Cisplatin + Perifosine
Indication/Tumor Type	ovarian clear cell carcinoma
Response Type	predicted – sensitive

combination therapy	Ipatasertib + Paclitaxel
Indication/Tumor Type	triple-receptor negative breast cancer
Response Type	predicted – sensitive

Response Type	sensitive
combination therapy	MK2206 + Vemurafenib
Evidence Type	Actionable

Indication/Tumor Type	lymphoma
Response Type	decreased response
Approval Status	Preclinical - Cell line xenograft

Indication/Tumor Type	Advanced Solid Tumor
Response Type	predicted – sensitive
Approval Status	Preclinical - Cell line xenograft

combination therapy	Cetuximab + Irinotecan
Indication/Tumor Type	colorectal cancer
Response Type	resistant

Indication/Tumor Type	breast cancer
Response Type	resistant
Approval Status	Preclinical - Cell culture

combination therapy	Capivasertib + Fulvestrant
Indication/Tumor Type	Her2-receptor negative breast cancer
Response Type	sensitive

combination therapy	Cisplatin + Gemcitabine + Sorafenib
Indication/Tumor Type	invasive bladder transitional cell carcinoma
Response Type	predicted – resistant

Indication/Tumor Type	endometrial cancer
Response Type	sensitive
Approval Status	Phase II

RAC-ALPHA SERINE/THREONINE-PROTEIN KINASE (EC 2.7.1.37) (RAC-PK-ALPHA) (PROTEIN KINASE B) (PKB) (C-AKT). [SOURCE:UNIPROT/SWISSPROT;ACC:P31749]	Description
ENSG00000142208	Ensembl Gene Id
AKT1	Display Id

P31749	Uniprot Accession
RAC-ALPHA SERINE/THREONINE-PROTEIN KINASE	Uniprot Protein Name
207	Entrez Gene Id

v-akt murine thymoma viral oncogene homolog 1	HUGO Gene Name
391	HUGO Gene ID
AKT1	Gene Symbol

AKT1	DrugBank Gene Name
P31749	UniProt Accession
207	Entrez Gene Id

AKT1 Gene Record

AKT1 207 Druggable GenomeClinically Actionable

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Approval Status Phase II Response Type predicted – sensitive Indication/Tumor Type triple-receptor negative breast cancer

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor Specific Action of the Ligand Inhibition

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? True

Publications: Lee D et al., 2017, AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells., Onco Targets Ther

Interaction Types & Directionality: inhibitor (inhibitory) allosteric modulator inhibitory allosteric modulator (inhibitory)

Interaction Info: Notes combination therapy MK2206 + Vemurafenib Indication/Tumor Type melanoma

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type ovarian cancer Evidence Type Actionable Approval Status Phase I

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name perifosine, KRX-0401 Novel drug target Novel Target Indication/Tumor Type ovarian clear cell carcinoma

Publications: Sasano et al., 2015, Preclinical Efficacy for AKT Targeting in Clear Cell Carcinoma of the Ovary., Mol. Cancer Res. Shome D et al., 2008, Ulcerative keratitis in gastrointestinal stromal tumor patients treated with perifosine., Ophthalmology

Interaction Types & Directionality: allosteric modulator inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? True

Publications: Leoni C et al., 2019, First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma., Am J Med Genet A Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction? True Endogenous Drug? False Specific Action of the Ligand Inhibition

Publications: Okuzumi T et al., 2009, Inhibitor hijacking of Akt activation., Nat Chem Biol

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor Specific Action of the Ligand Inhibition

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? True

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor Novel drug target Novel Target

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Evidence Type Actionable Approval Status Phase Ib/II Response Type sensitive

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Notes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Notes

Publications:

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Cisplatin + Perifosine Indication/Tumor Type ovarian clear cell carcinoma Response Type predicted – sensitive

Interaction Types & Directionality: n/a

Interaction Info: Response Type predicted – sensitive combination therapy Doxorubicin + Sirolimus Evidence Type Actionable

Publications: Mavrakis et al., 2008, Tumorigenic activity and therapeutic inhibition of Rheb GTPase., Genes Dev.

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Ipatasertib + Paclitaxel Indication/Tumor Type triple-receptor negative breast cancer Response Type predicted – sensitive

Publications: Schmid P et al., 2020, Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial., J Clin Oncol

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Phase II Response Type predicted – sensitive

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Approval Status Phase II

Response Type predicted – sensitive

Indication/Tumor Type triple-receptor negative breast cancer

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Specific Action of the Ligand Inhibition

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:

Lee D et al., 2017, AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells., Onco Targets Ther

Interaction Types & Directionality:

inhibitor (inhibitory)

allosteric modulator

inhibitory allosteric modulator (inhibitory)

Interaction Info:

Notes

combination therapy MK2206 + Vemurafenib

Indication/Tumor Type melanoma

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type ovarian cancer

Evidence Type Actionable

Approval Status Phase I

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name perifosine, KRX-0401

Novel drug target Novel Target

Indication/Tumor Type ovarian clear cell carcinoma

Publications:

Sasano et al., 2015, Preclinical Efficacy for AKT Targeting in Clear Cell Carcinoma of the Ovary., Mol. Cancer Res.

Shome D et al., 2008, Ulcerative keratitis in gastrointestinal stromal tumor patients treated with perifosine., Ophthalmology

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:

Leoni C et al., 2019, First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma., Am J Med Genet A

Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:

Okuzumi T et al., 2009, Inhibitor hijacking of Akt activation., Nat Chem Biol

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Specific Action of the Ligand Inhibition

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Novel drug target Novel Target

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Phase Ib/II

Response Type sensitive

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase AKT inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cisplatin + Perifosine

Indication/Tumor Type ovarian clear cell carcinoma

Response Type predicted – sensitive

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type predicted – sensitive

combination therapy Doxorubicin + Sirolimus

Evidence Type Actionable

Publications:

Mavrakis et al., 2008, Tumorigenic activity and therapeutic inhibition of Rheb GTPase., Genes Dev.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ipatasertib + Paclitaxel

Indication/Tumor Type triple-receptor negative breast cancer

Response Type predicted – sensitive

Publications:

Schmid P et al., 2020, Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial., J Clin Oncol

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Phase II

Response Type predicted – sensitive

Publications:

Myers et al., 2016, Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology Group study., Gynecol. Oncol.

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy MK2206 + Vemurafenib

Evidence Type Actionable

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Phase I

Response Type no benefit

Publications:

Garrett et al., 2011, Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT., Invest New Drugs

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type resistant

Publications:

Le et al., 2016, Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer., Cancer Discov

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lymphoma

Response Type decreased response

Approval Status Preclinical - Cell line xenograft

Publications:

Mavrakis et al., 2008, Tumorigenic activity and therapeutic inhibition of Rheb GTPase., Genes Dev.

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type predicted – sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Allen et al., 2013, Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects., Sci Transl Med

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Irinotecan

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Hechtman et al., 2015, AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants., Mol. Cancer Res.

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Irinotecan

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Hechtman et al., 2015, AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants., Mol. Cancer Res.

207	Entrez Gene Id
AKT1	MyCancerGenome Gene Symbol
AKT	MyCancerGenome Reported Gene Name

RAC	GENE_SYMBOL
AKT1	GENE_SYMBOL
RAC-alpha serine/threonine-protein kinase	UNIPROT

AKT serine/threonine kinase 1	GuideToPharmacology Name
P31749	UniProtKB ID

207	OncoKB Entrez Id
PRKBA	OncoKB Gene Synonym
RAC	OncoKB Gene Synonym

ENSG00000142208	Ensembl Gene ID
AKT	Human Protein Atlas Gene Synonym
PKB	Human Protein Atlas Gene Synonym

RAC-alpha serine/threonine-protein kinase	Gene Name
P31749	UniProt ID