DGIdb - SELUMETINIB Drug Record

SELUMETINIB chembl:CHEMBL1614701 Antineoplastic

Alternate Names:

ARRY-886
SELUMETINIB
ARRY-142886
AZD-6244
KOSELUGO
AZD 6244
AZD6244
NSC 741O78
ARRY 142886
ARRY142886
drugbank:11689
pubchem.compound:10127622
chembl:CHEMBL1614701
chemidplus:606143-52-6

Drug Info:

Pharmaceutical Developer	AstraZenica
Source Reported Drug Name(s)	AZD6244/selumetinib
Drug Class	MEK Inhibitor
Notes	allosteric inhibitor
Drug Class	Kinase Inhibitors

(11 More Sources)

Publications:

Grisham et al., 2015, Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer., J. Clin. Oncol.
Emery et al., 2009, MEK1 mutations confer resistance to MEK and B-RAF inhibition., Proc. Natl. Acad. Sci. U.S.A.
Marks et al., 2008, Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma., Cancer Res.
Crystal et al., 2014, Patient-derived models of acquired resistance can identify effective drug combinations for cancer., Science
Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.
Nikolaev et al., 2011, Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma., Nat. Genet.
Gannon et al., 2016, Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy., Mol. Cancer Res.
Choi et al., 2012, Oncogenic MAP2K1 mutations in human epithelial tumors., Carcinogenesis
Narita et al., 2014, Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model., Mol. Cancer Ther.
Catalanotti F et al., 2013, Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma., Clin Cancer Res
Yeh et al., 2007, Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor., Clin. Cancer Res.
Dombi et al., 2016, Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas., N. Engl. J. Med.
Davies et al., 2007, AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models., Mol. Cancer Ther.
Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.
Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget
Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov
Bonnevaux et al., 2016, Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor., Mol. Cancer Ther.
Whittaker et al., 2015, Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors., Mol. Cancer Ther.
Ho et al., 2013, Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer., N. Engl. J. Med.
McNew et al., 2016, MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling., Mol. Cancer Res.
Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol
Beloueche-Babari et al., 2013, Acute tumour response to the MEK1/2 inhibitor selumetinib (AZD6244, ARRY-142886) evaluated by non-invasive diffusion-weighted MRI., Br. J. Cancer
Friedman et al., 2015, Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment., PLoS ONE
Olow et al., 2016, BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas., Clin. Cancer Res.
Kirkwood et al., 2012, Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma., Clin. Cancer Res.
Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell
Fangusaro J et al., 2019, Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial., Lancet Oncol
Cheng et al., 2015, Paracrine Effect of NRG1 and HGF Drives Resistance to MEK Inhibitors in Metastatic Uveal Melanoma., Cancer Res.
Qu et al., 2014, Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft models., J. Exp. Clin. Cancer Res.
de Martino et al., 2014, Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib., Cancer Biol. Ther.
Kaufman et al., 2017, A Transcriptional Signature Identifies LKB1 Functional Status as a Novel Determinant of MEK Sensitivity in Lung Adenocarcinoma., Cancer Res.
Chen et al., 2012, A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response., Nature
Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.
Nakanishi et al., 2015, ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor., Mol. Cancer Ther.
Dhawan et al., 2016, Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling., Nature
Takekuma et al., 2016, A long-term surviving patient with recurrent low-grade serous ovarian carcinoma treated with the MEK1/2 inhibitor, selumetinib., Gynecol Oncol Res Pract
Jänne et al., 2015, Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer., Br. J. Cancer
Papadimitrakopoulou et al., 2016, The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer., J. Clin. Oncol.
Qian et al., 2014, Whole genome gene copy number profiling of gastric cancer identifies PAK1 and KRAS gene amplification as therapy targets., Genes Chromosomes Cancer
Jänne et al., 2013, Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study., Lancet Oncol.
Jänne et al., 2017, Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial., JAMA
Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
Holt et al., 2012, Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055)., Cancer Res.
Engelman et al., 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers., Nat. Med.
Hofmann et al., 2012, K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo., PLoS ONE
García-García et al., 2015, MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer., Clin. Cancer Res.
Depreeuw et al., 2015, Characterization of patient-derived tumor xenograft models of endometrial cancer for preclinical evaluation of targeted therapies., Gynecol. Oncol.
Riquelme et al., 2016, Modulation of EZH2 Expression by MEK-ERK or PI3K-AKT Signaling in Lung Cancer Is Dictated by Different KRAS Oncogene Mutations., Cancer Res.
Kim et al., 2016, Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS-Mutant Lung Cancer., Mol. Cancer Res.
Deming et al., 2016, A phase I study of selumetinib (AZD6244/ARRY-142866), a MEK1/2 inhibitor, in combination with cetuximab in refractory solid tumors and KRAS mutant colorectal cancer., Invest New Drugs
Hochster et al., 2015, Phase II study of selumetinib (AZD6244, ARRY-142886) plus irinotecan as second-line therapy in patients with K-RAS mutated colorectal cancer., Cancer Chemother. Pharmacol.
Ebi et al., 2011, Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers., J. Clin. Invest.
Lamba et al., 2014, RAF suppression synergizes with MEK inhibition in KRAS mutant cancer cells., Cell Rep
Migliardi et al., 2012, Inhibition of MEK and PI3K/mTOR suppresses tumor growth but does not cause tumor regression in patient-derived xenografts of RAS-mutant colorectal carcinomas., Clin. Cancer Res.
Weigelt et al., 2011, PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs., Oncogene
Ohashi et al., 2013, Characteristics of lung cancers harboring NRAS mutations., Clin. Cancer Res.
Ambrosini et al., 2012, Identification of unique MEK-dependent genes in GNAQ mutant uveal melanoma involved in cell growth, tumor cell invasion, and MEK resistance., Clin. Cancer Res.
Khalili et al., 2012, Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner., Clin. Cancer Res.
Wu et al., 2012, The protein kinase C inhibitor enzastaurin exhibits antitumor activity against uveal melanoma., PLoS ONE
Landis et al., 1989, GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours., Nature
Ho et al., 2012, Impact of combined mTOR and MEK inhibition in uveal melanoma is driven by tumor genotype., PLoS ONE
Wu et al., 2012, Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-κB pathways., Mol. Cancer Ther.
Van Raamsdonk et al., 2010, Mutations in GNA11 in uveal melanoma., N. Engl. J. Med.
Van Raamsdonk et al., 2009, Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi., Nature
Onken et al., 2008, Oncogenic mutations in GNAQ occur early in uveal melanoma., Invest. Ophthalmol. Vis. Sci.
Kalinec et al., 1992, Mutated alpha subunit of the Gq protein induces malignant transformation in NIH 3T3 cells., Mol. Cell. Biol.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Patel et al., 2011, Therapeutic implications of the emerging molecular biology of uveal melanoma., Clin. Cancer Res.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Chen et al., 2014, Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations., Oncogene
Garcia-Rendueles et al., 2015, NF2 Loss Promotes Oncogenic RAS-Induced Thyroid Cancers via YAP-Dependent Transactivation of RAS Proteins and Sensitizes Them to MEK Inhibition., Cancer Discov
Ko et al., 2016, A Multicenter, Open-Label Phase II Clinical Trial of Combined MEK plus EGFR Inhibition for Chemotherapy-Refractory Advanced Pancreatic Adenocarcinoma., Clin. Cancer Res.
Yoon et al., 2009, Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells., Mol. Cancer Ther.
Sun et al., 2014, Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3., Cell Rep
Ambrosini et al., 2014, Overexpression of DDX43 mediates MEK inhibitor resistance through RAS Upregulation in uveal melanoma cells., Mol. Cancer Ther.
Ichihara et al., 2017, SFK/FAK Signaling Attenuates Osimertinib Efficacy in Both Drug-Sensitive and Drug-Resistant Models of EGFR-Mutant Lung Cancer., Cancer Res.
Challa et al., 2016, IKBKE Is a Substrate of EGFR and a Therapeutic Target in Non-Small Cell Lung Cancer with Activating Mutations of EGFR., Cancer Res.
Berger et al., 2014, Oncogenic RIT1 mutations in lung adenocarcinoma., Oncogene
Smida et al., 2016, MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated., Nat Commun
Johannessen et al., 2013, A melanocyte lineage program confers resistance to MAP kinase pathway inhibition., Nature
Wang et al., 2017, ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition., Cell Rep

SELUMETINIB GNA11

Interaction Score: 2.21

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status early trials

Pathway activation

Variant Effect gain-of-function

PMIDs:
21444680 26619011 24141786 2549426 22733540 25157968 1328859 22808163 21083380

Sources:
DoCM
SELUMETINIB RIT1

Interaction Score: 1.77

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24469055

Sources:
CIViC
SELUMETINIB DDX43

Interaction Score: 1.77

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24899684

Sources:
CIViC
SELUMETINIB GNAQ

Interaction Score: 1.77

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
22550165 22733540 22253748 2549426 22808163 22653968 21083380 19078957 18719078 1328859 25157968

Sources:
JAX-CKB DoCM
SELUMETINIB CIC

Interaction Score: 1.18

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
28178529

Sources:
CIViC
SELUMETINIB NF1

Interaction Score: 0.88

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
28029918 31151904

Sources:
ClearityFoundationBiomarkers CIViC
SELUMETINIB MAP2K1

Interaction Score: 0.81

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Indication/Tumor Type melanoma

Response Type resistant

PMIDs:
26324360 19915144 18632602 25394791 27312529 22197931 26582713 22327936 24448821 23444215 17332304 28029918 17699718

Sources:
TALC MyCancerGenome ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions COSMIC CIViC CancerCommons MyCancerGenomeClinicalTrial TTD
SELUMETINIB CDH1

Interaction Score: 0.71

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Erlotinib + Selumetinib

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

PMIDs:
26251290

Sources:
JAX-CKB
SELUMETINIB NF2

Interaction Score: 0.71

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26359368

Sources:
CIViC
SELUMETINIB EZH2

Interaction Score: 0.5

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy DZNep + Selumetinib

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

PMIDs:
26676756

Sources:
JAX-CKB
SELUMETINIB KRAS

Interaction Score: 0.41

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Osimertinib + Selumetinib

Indication/Tumor Type thyroid cancer

combination therapy Dasatinib + Selumetinib

PMIDs:
25870145 27222538 26438159 27312529 27556948 27231576 26351322 26125448 27480147 24935174 23200175 28492898 26725216 27655129 24939055 22271687 19029981 22952903 26272063 26232337 26676756 27422710 26666244 25322874 21985784 25199829 22392911

Sources:
ClearityFoundationBiomarkers JAX-CKB CIViC MyCancerGenomeClinicalTrial
SELUMETINIB MAP2K2

Interaction Score: 0.4

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 2 inhibitor

Direct Interaction yes

PMIDs:
17332304 28029918 17699718

Sources:
TALC MyCancerGenome ClearityFoundationClinicalTrial ChemblInteractions MyCancerGenomeClinicalTrial TTD
SELUMETINIB BRAF

Interaction Score: 0.36

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type decreased response

Approval Status Preclinical

PMIDs:
24265152 27196754 26351322 23406027 27655129 26137449 22197931 24448821 23942066 26461489 27222538 27312529 19915144 27217440 22048237 26343583 31151904

Sources:
ClearityFoundationBiomarkers JAX-CKB CIViC
SELUMETINIB MAP2K5

Interaction Score: 0.35

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
SELUMETINIB STK11

Interaction Score: 0.31

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
27821489 22425996

Sources:
JAX-CKB CIViC
SELUMETINIB NRAS

Interaction Score: 0.3

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Phase I

PMIDs:
23406027 25870145 26343583 22392911 23515407

Sources:
JAX-CKB CIViC OncoKB
SELUMETINIB MAP2K4

Interaction Score: 0.29

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
SELUMETINIB MAP2K7

Interaction Score: 0.29

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
SELUMETINIB MAP2K6

Interaction Score: 0.29

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
SELUMETINIB MAP2K3

Interaction Score: 0.29

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
SELUMETINIB HRAS

Interaction Score: 0.21

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung squamous cell carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

PMIDs:
27222538 26544513

Sources:
JAX-CKB CIViC
SELUMETINIB ERBB3

Interaction Score: 0.18

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24685132 25952648

Sources:
CIViC
SELUMETINIB FGFR2

Interaction Score: 0.1

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type decreased response

Indication/Tumor Type endometrial carcinoma

Approval Status Preclinical - Cell culture

PMIDs:
26438159 19755509

Sources:
JAX-CKB
SELUMETINIB PIK3CA

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type predicted – sensitive

Indication/Tumor Type endometrial cancer

combination therapy Selumetinib + ZSTK474

PMIDs:
26232337 26137449 21358673 26272063 24939055 22271687

Sources:
JAX-CKB
SELUMETINIB PTEN

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Selumetinib + BEZ235

Indication/Tumor Type endometrial cancer

Response Type sensitive

PMIDs:
27196754 21358673 26232337

Sources:
JAX-CKB
SELUMETINIB MET

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Selumetinib + BEZ235

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
25952648 24939055

Sources:
JAX-CKB CIViC
SELUMETINIB MITF

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24185007

Sources:
CIViC
SELUMETINIB ATM

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
27922010

Sources:
CIViC
SELUMETINIB ALK

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ceritinib + Selumetinib

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
25394791

Sources:
JAX-CKB
SELUMETINIB SRC

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dasatinib + Selumetinib

Indication/Tumor Type thyroid cancer

Response Type sensitive

PMIDs:
27222538

Sources:
JAX-CKB
SELUMETINIB EGFR

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Osimertinib + Selumetinib

Indication/Tumor Type lung adenocarcinoma

Approval Status Preclinical

PMIDs:
24939055 28416483 25870145 27287717 27312529

Sources:
JAX-CKB
SELUMETINIB FGFR3

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type urinary bladder cancer

Response Type no benefit

Approval Status Preclinical

PMIDs:
26438159

Sources:
JAX-CKB
SELUMETINIB FGFR1

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung squamous cell carcinoma

Response Type no benefit

Approval Status Preclinical - Cell culture

PMIDs:
26438159

Sources:
JAX-CKB
SELUMETINIB ERBB2

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type decreased response

PMIDs:
24971884

Sources:
JAX-CKB
SELUMETINIB TP53

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type decreased response

Approval Status Preclinical - Pdx

PMIDs:
26343583 26272063 22425996

Sources:
JAX-CKB CIViC

CancerCommons: AZD6244
- Version: 25-July-2013
Alternate Names:

AZD6244 PubChem Drug Name

10127622 PubChem Drug ID

Selumetinib Drug Trade Name

Drug Info:

Drug Class MEK Inhibitor

Source Reported Drug Name(s) AZD6244/selumetinib

Pharmaceutical Developer AstraZenica

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

AZD6244 Development Name

ARRY-142886 Development Name

SELUMETINIB Generic Name

Drug Info:

Drug Class Kinase Inhibitors

Notes allosteric inhibitor

Publications:

JAX-CKB: Selumetinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Kiessling et al., 2015, Mutant HRAS as novel target for MEK and mTOR inhibitors., Oncotarget

Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.

García-García et al., 2015, MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer., Clin. Cancer Res.

DoCM: SELUMETINIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Landis et al., 1989, GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours., Nature

Wu et al., 2012, Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-κB pathways., Mol. Cancer Ther.

Ho et al., 2012, Impact of combined mTOR and MEK inhibition in uveal melanoma is driven by tumor genotype., PLoS ONE

CIViC: SELUMETINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Jänne et al., 2013, Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study., Lancet Oncol.

Engelman et al., 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers., Nat. Med.

Lamba et al., 2014, RAF suppression synergizes with MEK inhibition in KRAS mutant cancer cells., Cell Rep

TALC: SELUMETINIB
- Version: 12-May-2016
Alternate Names:

SELUMETINIB Primary Drug Name

SELUMETINIB Drug Generic Name

AZD6244 Drug Synonym

Drug Info:

Publications:
TTD: AZD6244
- Version: 2020.06.01
Alternate Names:

D0T5DP TTD Drug ID

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL1614701
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
ChemblInteractions: CHEMBL1614701
- Version: chembl_23
Alternate Names:

Drug Info:

Publications:
MyCancerGenomeClinicalTrial: AZD6244
- Version: 30-February-2014
Alternate Names:

Drug Info:

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

Drug Info:

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

Drug Info:

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

Drug Info:

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

Drug Info:

Publications:
COSMIC: Selumetinib
- Version: 4-Sep-2020
Alternate Names:

Drug Info:

Publications:

Clinical Status	early trials
Pathway	activation
Variant Effect	gain-of-function

Evidence Type	Actionable
Approval Status	Preclinical - Cell culture
Response Type	sensitive

Reported Cancer Type	Melanoma
Indication/Tumor Type	melanoma
Response Type	resistant

combination therapy	Erlotinib + Selumetinib
Indication/Tumor Type	pancreatic ductal adenocarcinoma
Response Type	sensitive

combination therapy	DZNep + Selumetinib
Indication/Tumor Type	lung adenocarcinoma
Response Type	sensitive

combination therapy	Osimertinib + Selumetinib
Indication/Tumor Type	thyroid cancer
combination therapy	Dasatinib + Selumetinib

Notes
Mechanism of Interaction	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
Direct Interaction	yes

Indication/Tumor Type	non-small cell lung carcinoma
Response Type	resistant
Approval Status	Phase I

Indication/Tumor Type	lung squamous cell carcinoma
Response Type	sensitive
Approval Status	Preclinical - Cell line xenograft

Response Type	decreased response
Indication/Tumor Type	endometrial carcinoma
Approval Status	Preclinical - Cell culture

allosteric modulator
inhibitor (inhibitory)

Response Type	predicted – sensitive
Indication/Tumor Type	endometrial cancer
combination therapy	Selumetinib + ZSTK474

combination therapy	Selumetinib + BEZ235
Indication/Tumor Type	endometrial cancer
Response Type	sensitive

combination therapy	Ceritinib + Selumetinib
Indication/Tumor Type	non-small cell lung carcinoma
Response Type	sensitive

Indication/Tumor Type	urinary bladder cancer
Response Type	no benefit
Approval Status	Preclinical

Indication/Tumor Type	colorectal cancer
Response Type	decreased response
Approval Status	Preclinical - Pdx

AZD6244	PubChem Drug Name
10127622	PubChem Drug ID
Selumetinib	Drug Trade Name

AZD6244	Development Name
ARRY-142886	Development Name
SELUMETINIB	Generic Name

SELUMETINIB	Primary Drug Name
SELUMETINIB	Drug Generic Name
AZD6244	Drug Synonym

SELUMETINIB Drug Record

SELUMETINIB chembl:CHEMBL1614701 Antineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info: Clinical Status early trials Pathway activation Variant Effect gain-of-function

PMIDs: 21444680 26619011 24141786 2549426 22733540 25157968 1328859 22808163 21083380

Sources: DoCM

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24469055

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24899684

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell culture Response Type sensitive

PMIDs: 22550165 22733540 22253748 2549426 22808163 22653968 21083380 19078957 18719078 1328859 25157968

Sources: JAX-CKB DoCM

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 28178529

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 28029918 31151904

Sources: ClearityFoundationBiomarkers CIViC

Interaction Types & Directionality: allosteric modulator inhibitor (inhibitory)

Interaction Info: Reported Cancer Type Melanoma Indication/Tumor Type melanoma Response Type resistant

PMIDs: 26324360 19915144 18632602 25394791 27312529 22197931 26582713 22327936 24448821 23444215 17332304 28029918 17699718

Sources: TALC MyCancerGenome ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions COSMIC CIViC CancerCommons MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Erlotinib + Selumetinib Indication/Tumor Type pancreatic ductal adenocarcinoma Response Type sensitive

PMIDs: 26251290

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 26359368

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: combination therapy DZNep + Selumetinib Indication/Tumor Type lung adenocarcinoma Response Type sensitive

PMIDs: 26676756

Sources: JAX-CKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: combination therapy Osimertinib + Selumetinib Indication/Tumor Type thyroid cancer combination therapy Dasatinib + Selumetinib

PMIDs: 25870145 27222538 26438159 27312529 27556948 27231576 26351322 26125448 27480147 24935174 23200175 28492898 26725216 27655129 24939055 22271687 19029981 22952903 26272063 26232337 26676756 27422710 26666244 25322874 21985784 25199829 22392911

Sources: ClearityFoundationBiomarkers JAX-CKB CIViC MyCancerGenomeClinicalTrial

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Notes Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 2 inhibitor Direct Interaction yes

PMIDs: 17332304 28029918 17699718

Sources: TALC MyCancerGenome ClearityFoundationClinicalTrial ChemblInteractions MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type decreased response Approval Status Preclinical

PMIDs: 24265152 27196754 26351322 23406027 27655129 26137449 22197931 24448821 23942066 26461489 27222538 27312529 19915144 27217440 22048237 26343583 31151904

Sources: ClearityFoundationBiomarkers JAX-CKB CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Sources: MyCancerGenomeClinicalTrial

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell culture Response Type sensitive

PMIDs: 27821489 22425996

Sources: JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type resistant Approval Status Phase I

PMIDs: 23406027 25870145 26343583 22392911 23515407

Sources: JAX-CKB CIViC OncoKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Sources: MyCancerGenomeClinicalTrial

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Sources: MyCancerGenomeClinicalTrial

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status early trials

Pathway activation

Variant Effect gain-of-function

PMIDs:
21444680 26619011 24141786 2549426 22733540 25157968 1328859 22808163 21083380

Sources:
DoCM

Interaction Types & Directionality:

n/a

PMIDs:
24469055

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24899684

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
22550165 22733540 22253748 2549426 22808163 22653968 21083380 19078957 18719078 1328859 25157968

Sources:
JAX-CKB DoCM

Interaction Types & Directionality:

n/a

PMIDs:
28178529

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
28029918 31151904

Sources:
ClearityFoundationBiomarkers CIViC

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Indication/Tumor Type melanoma

Response Type resistant

PMIDs:
26324360 19915144 18632602 25394791 27312529 22197931 26582713 22327936 24448821 23444215 17332304 28029918 17699718

Sources:
TALC MyCancerGenome ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions COSMIC CIViC CancerCommons MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Erlotinib + Selumetinib

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

PMIDs:
26251290

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
26359368

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy DZNep + Selumetinib

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

PMIDs:
26676756

Sources:
JAX-CKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Osimertinib + Selumetinib

Indication/Tumor Type thyroid cancer

combination therapy Dasatinib + Selumetinib

PMIDs:
25870145 27222538 26438159 27312529 27556948 27231576 26351322 26125448 27480147 24935174 23200175 28492898 26725216 27655129 24939055 22271687 19029981 22952903 26272063 26232337 26676756 27422710 26666244 25322874 21985784 25199829 22392911

Sources:
ClearityFoundationBiomarkers JAX-CKB CIViC MyCancerGenomeClinicalTrial

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 2 inhibitor

Direct Interaction yes

PMIDs:
17332304 28029918 17699718

Sources:
TALC MyCancerGenome ClearityFoundationClinicalTrial ChemblInteractions MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type decreased response

Approval Status Preclinical

PMIDs:
24265152 27196754 26351322 23406027 27655129 26137449 22197931 24448821 23942066 26461489 27222538 27312529 19915144 27217440 22048237 26343583 31151904

Sources:
ClearityFoundationBiomarkers JAX-CKB CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
27821489 22425996

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Phase I

PMIDs:
23406027 25870145 26343583 22392911 23515407

Sources:
JAX-CKB CIViC OncoKB

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung squamous cell carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

PMIDs:
27222538 26544513

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24685132 25952648

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type decreased response

Indication/Tumor Type endometrial carcinoma

Approval Status Preclinical - Cell culture

PMIDs:
26438159 19755509