DGIdb - RET Gene Record

RET 5979 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

5979
RET PROTO-ONCOGENE
RET
CDHF12
CDHR16
HSCR1
MEN2A
MEN2B
MTC1
PTC
RET-ELE1
164761
9967
ENSG00000165731
OTTHUMG00000018024
BE0002411
P07949
RET51
RET_HUMAN
PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET PRECURSOR (EC 2.7.1.112) (C-RET). [SOURCE:UNIPROT/SWISSPROT;ACC:P07949]
SOLUBLE RET KINASE FRAGMENT
BE0001104
O43519
2185
NP_065681
NM_020630
42
TTDS00348
C-RET
PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET
RET RECEPTOR TYROSINE KINASE
Proto-oncogene c-Ret
Cadherin family member 12
Extracellular cell-membrane anchored RET cadherin 120 kDa fragment
PA34335
T60631

Gene Info:

Human Readable Name	TYROSINE KINASE
Target Class	Receptors
Target Subclass	EC:2.7.10.1
Initial Gene Query	RET
Counted Citations from 1950-2000	2777
Human Readable Name	DRUGGABLE GENOME
Uniprot Status	Swiss-Prot
Interpro Type	Domain
Interpro Short Name	Ser-Thr/Tyr_kinase_cat_dom
Interpro Name	Serine-threonine/tyrosine-protein kinase catalytic domain
Uniprot Evidence	1: Evidence at protein level
Human Readable Name	KINASE
Interpro Acc	IPR001245
GuideToPharmacology Gene Category Name	Type XIV RTKs: RET
GuideToPharmacology Gene Category ID	794
GuideToPharmacology Gene Type	catalytic_receptor
Source Reported Gene Name	RET
Target Subclass	Kinase
Target Main Class	Receptors
Target Subclass	Other
Transmembrane Helix Count	1
Gene Biotype	PROTEIN_CODING

(29 More Sources)

Gene Categories: Category Details

KINASE
TYROSINE KINASE
DRUG RESISTANCE
DRUGGABLE GENOME
CLINICALLY ACTIONABLE

Publications:

Kato et al., 2017, RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients., Clin. Cancer Res.
Dabir et al., 2014, RET mutation and expression in small-cell lung cancer., J Thorac Oncol
Gautschi et al., 2017, Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry., J. Clin. Oncol.
Carlomagno et al., 2004, Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors., Oncogene
Carlomagno et al., 2009, Identification of tyrosine 806 as a molecular determinant of RET kinase sensitivity to ZD6474., Endocr. Relat. Cancer
Ehmann F et al., 2014, European Medicines Agency initiatives and perspectives on pharmacogenomics., Br J Clin Pharmacol
Gupta-Abramson et al., 2008, Phase II trial of sorafenib in advanced thyroid cancer., J. Clin. Oncol.
Santoro et al., 1998, Molecular biology of the MEN2 gene., J. Intern. Med.
Egawa et al., 1998, Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan., Jpn. J. Clin. Oncol.
Carr et al., 2010, Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation., Clin. Cancer Res.
Kloos et al., 2009, Phase II trial of sorafenib in metastatic thyroid cancer., J. Clin. Oncol.
Elisei et al., 2008, Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study., J. Clin. Endocrinol. Metab.
Sherman, 2011, Targeted therapies for thyroid tumors., Mod. Pathol.
Lam et al., 2010, Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer., J. Clin. Oncol.
Frisk et al., 2001, CGH alterations in medullary thyroid carcinomas in relation to the RET M918T mutation and clinical outcome., Int. J. Oncol.
Coxon et al., 2012, Anti-tumor activity of motesanib in a medullary thyroid cancer model., J. Endocrinol. Invest.
Verbeek et al., 2011, The effects of four different tyrosine kinase inhibitors on medullary and papillary thyroid cancer cells., J. Clin. Endocrinol. Metab.
Vitagliano et al., 2011, The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells., Endocr. Relat. Cancer
Couto et al., 2012, AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer cell lines., PLoS ONE
Wells et al., 2012, Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial., J. Clin. Oncol.
Wells et al., 2010, Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer., J. Clin. Oncol.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Yoh et al., 2017, Vandetanib in patients with previously treated RET-rearranged advanced non-small-cell lung cancer (LURET): an open-label, multicentre phase 2 trial., Lancet Respir Med
Lee et al., 2017, Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial., Ann. Oncol.
Renaud et al., 1975, Effects of 5,6-dihydroxytryptamine on tyrosine-hydroxylase activity in central catecholaminergic neurons of the rat., Biochem. Pharmacol.
Wilson et al., 1976, Some properties of the redox components of cytochrome c oxidase and their interactions., Arch. Biochem. Biophys.
Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.
Falchook et al., 2016, Effect of the RET Inhibitor Vandetanib in a Patient With RET Fusion-Positive Metastatic Non-Small-Cell Lung Cancer., J. Clin. Oncol.
Gautschi et al., 2013, A patient with lung adenocarcinoma and RET fusion treated with vandetanib., J Thorac Oncol
Drilon et al., 2013, Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas., Cancer Discov
Subbiah V et al., 2018, Selective RET kinase inhibition for patients with RET-altered cancers., Ann Oncol
Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
de Groot et al., 2006, Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations., Surgery
Drilon et al., 2016, Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial., Lancet Oncol.
Sherman et al., 2016, Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer., Cancer
Kurzrock et al., 2011, Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer., J. Clin. Oncol.
Bentzien et al., 2013, In vitro and in vivo activity of cabozantinib (XL184), an inhibitor of RET, MET, and VEGFR2, in a model of medullary thyroid cancer., Thyroid
Schneider et al., 2015, Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial., Int J Endocrinol
Wilhelm et al., 2011, Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity., Int. J. Cancer
Gong L et al., 2017, PharmGKB summary: sorafenib pathways., Pharmacogenet Genomics
Carlomagno et al., 2006, BAY 43-9006 inhibition of oncogenic RET mutants., J. Natl. Cancer Inst.
Wilhelm et al., 2004, BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis., Cancer Res.
Wilhelm et al., 2006, Discovery and development of sorafenib: a multikinase inhibitor for treating cancer., Nat Rev Drug Discov
Apsel B et al., 2008, Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases., Nat Chem Biol
Plaza-Menacho et al., 2007, Sorafenib functions to potently suppress RET tyrosine kinase activity by direct enzymatic inhibition and promoting RET lysosomal degradation independent of proteasomal targeting., J. Biol. Chem.
Prazeres H et al., 2011, In vitro transforming potential, intracellular signaling properties, and sensitivity to a kinase inhibitor (sorafenib) of RET proto-oncogene variants Glu511Lys, Ser649Leu, and Arg886Trp., Endocr Relat Cancer
Tohyama et al., 2014, Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models., J Thyroid Res
Matsui et al., 2008, E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition., Int. J. Cancer
Subbiah V et al., 2018, Precision Targeted Therapy with BLU-667 for <i>RET</i>-Driven Cancers., Cancer Discov
Kim et al., 2006, An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases., J. Clin. Endocrinol. Metab.
Wang et al., 2016, Recurrent Olfactory Neuroblastoma Treated With Cetuximab and Sunitinib: A Case Report., Medicine (Baltimore)
Quek R et al., 2009, Gastrointestinal stromal tumor: a clinical overview., Hematol Oncol Clin North Am
Jones et al., 2010, Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors., Genome Biol.
Cooper AJ et al., 2020, Identification of a RAS-activating <i>TMEM87A-RASGRF1</i> Fusion in an Exceptional Responder to Sunitinib with Non-Small Cell Lung Cancer., Clin Cancer Res
Quintela-Fandino et al., 2014, Selective activity over a constitutively active RET-variant of the oral multikinase inhibitor dovitinib: results of the CNIO-BR002 phase I-trial., Mol Oncol
De Falco et al., 2013, Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer., J. Clin. Endocrinol. Metab.
Mologni et al., 2013, Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase., Mol. Cell. Endocrinol.
Drilon A et al., 2018, Frequency of Brain Metastases and Multikinase Inhibitor Outcomes in Patients With RET-Rearranged Lung Cancers., J Thorac Oncol
Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.
Lin et al., 2016, Clinical Activity of Alectinib in Advanced RET-Rearranged Non-Small Cell Lung Cancer., J Thorac Oncol
Pietrantonio F et al., 2018, RET fusions in a small subset of advanced colorectal cancers at risk of being neglected., Ann Oncol
Li et al., 2017, Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or Mutations., Clin. Cancer Res.
Drilon A et al., 2019, A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105., Cancer Discov
Marsee et al., 2004, Inhibition of heat shock protein 90, a novel RET/PTC1-associated protein, increases radioiodide accumulation in thyroid cells., J. Biol. Chem.
Cohen et al., 2002, Inhibition of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors., Surgery
Capes-Davis et al., 1999, Glucocorticoids differentially inhibit expression of the RET proto-oncogene., Gene Expr.
McCoach CE et al., 2018, Resistance Mechanisms to Targeted Therapies in <i>ROS1</i><sup>+</sup> and <i>ALK</i><sup>+</sup> Non-small Cell Lung Cancer., Clin Cancer Res
Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect

VANDETANIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Zactima

Novel drug target Established target

Direct Interaction? True

Publications:

Kato et al., 2017, RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients., Clin. Cancer Res.

Dabir et al., 2014, RET mutation and expression in small-cell lung cancer., J Thorac Oncol

Gautschi et al., 2017, Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry., J. Clin. Oncol.

CABOZANTINIB RET

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a biochemical assay.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Drilon et al., 2016, Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial., Lancet Oncol.

Sherman et al., 2016, Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer., Cancer

Kurzrock et al., 2011, Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer., J. Clin. Oncol.

REGORAFENIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Publications:

Wilhelm et al., 2011, Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity., Int. J. Cancer

SORAFENIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:

Gong L et al., 2017, PharmGKB summary: sorafenib pathways., Pharmacogenet Genomics

Carlomagno et al., 2006, BAY 43-9006 inhibition of oncogenic RET mutants., J. Natl. Cancer Inst.

Wilhelm et al., 2004, BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis., Cancer Res.

LENVATINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

Publications:

Tohyama et al., 2014, Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models., J Thyroid Res

Matsui et al., 2008, E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition., Int. J. Cancer

MOTESANIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type predicted – sensitive

Publications:

Coxon et al., 2012, Anti-tumor activity of motesanib in a medullary thyroid cancer model., J. Endocrinol. Invest.
PRALSETINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a biochemical assay.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Subbiah V et al., 2018, Precision Targeted Therapy with BLU-667 for RET-Driven Cancers., Cancer Discov

PONATINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:

Dabir et al., 2014, RET mutation and expression in small-cell lung cancer., J Thorac Oncol

De Falco et al., 2013, Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer., J. Clin. Endocrinol. Metab.

Mologni et al., 2013, Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase., Mol. Cell. Endocrinol.

CEP-32496 RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Indication/Tumor Type non-small cell lung carcinoma

Publications:

Pietrantonio F et al., 2018, RET fusions in a small subset of advanced colorectal cancers at risk of being neglected., Ann Oncol

Li et al., 2017, Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or Mutations., Clin. Cancer Res.

Drilon A et al., 2019, A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105., Cancer Discov

AST-487 RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In vitro inhibition of wild type RET.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:
AMUVATINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Trial Name MP-470

Novel drug target Established target

Publications:
CEP-11981 RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
RG-1530 RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
SORAFENIB TOSYLATE RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Publications:
LESTAURTINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Publications:
LINIFANIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name ABT-869, Linifanib

Novel drug target Established target

Specific Action of the Ligand Inhibition

Publications:
TAFETINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a radiometric biochemical protein kinase assay.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:
GILTERITINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:
QUIZARTINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
SUNITINIB MALATE RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Publications:
CEP-2563 RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Publications:
LUCITANIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
ALECTINIB HYDROCHLORIDE RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Publications:
RIVOCERANIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Assay used apatinib mesylate (YN968D1)

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:
IMATINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name imatinib mesylate, STI 571,Gleevec, Glivec

Novel drug target Established target

Publications:

de Groot et al., 2006, Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations., Surgery

SUNITINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Cetuximab + Sunitinib

Indication/Tumor Type olfactory neuroblastoma

Response Type sensitive

Publications:

Kim et al., 2006, An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases., J. Clin. Endocrinol. Metab.

Gautschi et al., 2017, Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry., J. Clin. Oncol.

Wang et al., 2016, Recurrent Olfactory Neuroblastoma Treated With Cetuximab and Sunitinib: A Case Report., Medicine (Baltimore)

HESPERADIN RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:

Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.
TOZASERTIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:

Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.
FOSTAMATINIB RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:

Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect
AT-9283 RET

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Publications:
ERDAFITINIB RET

Interaction Types & Directionality:

substrate

Interaction Info:

Publications:

EVEROLIMUS RET

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Phase II

Publications:

Kato et al., 2017, RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients., Clin. Cancer Res.

Schneider et al., 2015, Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial., Int J Endocrinol

Subbiah V et al., 2018, Selective RET kinase inhibition for patients with RET-altered cancers., Ann Oncol

DOVITINIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Phase I

Publications:

Quintela-Fandino et al., 2014, Selective activity over a constitutively active RET-variant of the oral multikinase inhibitor dovitinib: results of the CNIO-BR002 phase I-trial., Mol Oncol

ALECTINIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Approval Status Clinical Study

Publications:

Lin et al., 2016, Clinical Activity of Alectinib in Advanced RET-Rearranged Non-Small Cell Lung Cancer., J Thorac Oncol

Drilon A et al., 2018, Frequency of Brain Metastases and Multikinase Inhibitor Outcomes in Patients With RET-Rearranged Lung Cancers., J Thorac Oncol

Subbiah V et al., 2018, Selective RET kinase inhibition for patients with RET-altered cancers., Ann Oncol

CETUXIMAB RET

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Sunitinib

Indication/Tumor Type olfactory neuroblastoma

Response Type sensitive

Publications:

Wang et al., 2016, Recurrent Olfactory Neuroblastoma Treated With Cetuximab and Sunitinib: A Case Report., Medicine (Baltimore)
AZD-1480 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Couto et al., 2012, AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer cell lines., PLoS ONE
CRIZOTINIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Case Reports/Case Series

Response Type predicted - resistant

Publications:

McCoach CE et al., 2018, Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung Cancer., Clin Cancer Res
NINTEDANIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family Pan-TK inhibitor

Alteration RET__.

Publications:
ENMD-2076 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name ENMD-2076

Novel drug target Established target

Publications:
TANESPIMYCIN RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Marsee et al., 2004, Inhibition of heat shock protein 90, a novel RET/PTC1-associated protein, increases radioiodide accumulation in thyroid cells., J. Biol. Chem.
GENISTEIN RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Cohen et al., 2002, Inhibition of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors., Surgery
IMATINIB MESYLATE RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Cohen et al., 2002, Inhibition of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors., Surgery
DEXAMETHASONE RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Capes-Davis et al., 1999, Glucocorticoids differentially inhibit expression of the RET proto-oncogene., Gene Expr.
LAPATINIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
PAZOPANIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CYC-116 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
BARASERTIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
R-406 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
TAE-684 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
OSI-632 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
SNS-314 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
ERLOTINIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL1997335 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CEDIRANIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
AZD-1152-HQPA RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL202721 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL546797 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
PF-00562271 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
GW441756X RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
SITRAVATINIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
PALBOCICLIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
PD-0166285 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
ILORASERTIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
JNJ-7706621 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
SB-220025 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
ENTRECTINIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
ROMIPLOSTIM RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
ALISERTIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
SP-600125 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CENISERTIB RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL230686 RET

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ensembl: ENSG00000165731
- Version: 101_38
Alternate Names:

RET Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
TEND: P07949
- Version: 01-August-2011
Alternate Names:

5979 Entrez Gene Id

RET Gene Symbol

ENSG00000165731 Ensembl Gene Id

Gene Info:

Target Subclass Kinase

Target Main Class Receptors

Target Subclass Other

Publications:
TdgClinicalTrial: P07949
- Version: January-2014
Alternate Names:

RET Gene Symbol

Gene Info:

Target Class Receptors

Target Subclass EC:2.7.10.1

Publications:

RussLampel: ENSG00000165731

Version: 26-July-2011

Alternate Names:

PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET PRECURSOR (EC 2.7.1.112) (C-RET). [SOURCE:UNIPROT/SWISSPROT;ACC:P07949] Description

RET Display Id

ENSG00000165731 Ensembl Gene Id

Gene Info:

Human Readable Name DRUGGABLE GENOME

Gene Categories:

DRUGGABLE GENOME

Publications:

BaderLabGenes: RET
- Version: February-2014
Alternate Names:

5979 Entrez Gene ID

Gene Info:

Initial Gene Query RET

Counted Citations from 1950-2000 2777

Gene Categories:

KINASE

Publications:
GuideToPharmacologyGenes: 2185
- Version: 4-March-2015
Alternate Names:

ret proto-oncogene HUGO Gene Name

9967 HUGO Gene ID

RET Gene Symbol

Gene Info:

GuideToPharmacology Gene Category Name Type XIV RTKs: RET

GuideToPharmacology Gene Category ID 794

GuideToPharmacology Gene Type catalytic_receptor

Gene Categories:

KINASE, TYROSINE KINASE

Publications:
HopkinsGroom: P07949
- Version: 11-September-2012
Alternate Names:

RET_HUMAN Uniprot Id

SOLUBLE RET KINASE FRAGMENT Uniprot Protein Name

ENSG00000165731 Ensembl Gene Id

Gene Info:

Uniprot Status Swiss-Prot

Interpro Type Domain

Interpro Short Name Ser-Thr/Tyr_kinase_cat_dom

Gene Categories:

KINASE, DRUGGABLE GENOME

Publications:

PharmGKB: RET

Version: 18-August-2020

Alternate Names:

PA34335 PharmGKB ID

Gene Info:

Publications:

Gong L et al., 2017, PharmGKB summary: sorafenib pathways., Pharmacogenet Genomics

Quek R et al., 2009, Gastrointestinal stromal tumor: a clinical overview., Hematol Oncol Clin North Am

Ehmann F et al., 2014, European Medicines Agency initiatives and perspectives on pharmacogenomics., Br J Clin Pharmacol

JAX-CKB: RET

Version: 15-September-2020

Alternate Names:

5979 CKB Entrez Id

RET CKB Gene Synonym

CDHF12 CKB Gene Synonym

Gene Info:

Publications:

Frett et al., 2015, Fragment-Based Discovery of a Dual pan-RET/VEGFR2 Kinase Inhibitor Optimized for Single-Agent Polypharmacology., Angew. Chem. Int. Ed. Engl.

Moccia et al., 2015, Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase., PLoS ONE

Subbiah V et al., 2018, Selective RET kinase inhibition for patients with RET-altered cancers., Ann Oncol

DrugBank: BE0002411

Version: 5.1.7

Alternate Names:

RET DrugBank Gene Name

P07949 UniProt Accession

5979 Entrez Gene Id

Gene Info:

Publications:

Wilhelm et al., 2004, BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis., Cancer Res.

Carlomagno et al., 2006, BAY 43-9006 inhibition of oncogenic RET mutants., J. Natl. Cancer Inst.

Wilhelm et al., 2006, Discovery and development of sorafenib: a multikinase inhibitor for treating cancer., Nat Rev Drug Discov

DrugBank: BE0001104
- Version: 5.1.7
Alternate Names:

RET DrugBank Gene Name

O43519 UniProt Accession

5979 Entrez Gene Id

Gene Info:

Publications:

de Groot et al., 2006, Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations., Surgery

NCI: RET

Version: 14-September-2017

Alternate Names:

Gene Info:

Publications:

Cohen et al., 2002, Inhibition of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors., Surgery

Borrello et al., 2005, Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene., Proc. Natl. Acad. Sci. U.S.A.

Bunone et al., 1995, Induction of RET proto-oncogene expression in neuroblastoma cells precedes neuronal differentiation and is not mediated by protein synthesis., Exp. Cell Res.

DoCM: RET

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn

Wells et al., 2010, Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer., J. Clin. Oncol.

Wells et al., 2012, Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial., J. Clin. Oncol.

DTC: RET

Version: 02-September-2020

Alternate Names:

Gene Info:

Publications:

Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.

Apsel B et al., 2008, Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases., Nat Chem Biol

CGI: RET

Version: 14-September-2020

Alternate Names:

Gene Info:

Publications:

Wells et al., 2010, Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer., J. Clin. Oncol.

Wells et al., 2012, Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial., J. Clin. Oncol.

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

RET Gene Symbol

Gene Info:

Publications:
ChemblInteractions: CDHF12
- Version: chembl_23
Alternate Names:

CDHR16 GENE_SYMBOL

PTC GENE_SYMBOL

RET51 GENE_SYMBOL

Gene Info:

Publications:
HingoraniCasas: ENSG00000165731
- Version: 31-May-2017
Alternate Names:

ENSG00000165731 Gene Symbol

RET Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

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

5979 Entrez Gene Id

RET MyCancerGenome Gene Symbol

RET MyCancerGenome Reported Gene Name

Gene Info:

Publications:
GuideToPharmacologyInteractions: ENSG00000165731
- Version: 20-July-2020
Alternate Names:

ret proto-oncogene GuideToPharmacology Name

P07949 UniProtKB ID

Gene Info:

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

5979 OncoKB Entrez Id

MTC1 OncoKB Gene Synonym

CDHF12 OncoKB Gene Synonym

Gene Info:

Publications:
TTD: Proto-oncogene c-Ret
- Version: 2020.06.01
Alternate Names:

RET TTD Gene Abbreviation

T60631 TTD Target ID

Gene Info:

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

Proto-oncogene tyrosine-protein kinase receptor Ret Gene Name

P07949 UniProt ID

Gene Info:

Gene Categories:

KINASE

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

CDHF12 GO Gene Synonym

CDHR16 GO Gene Synonym

PTC GO Gene Synonym

Gene Info:

Gene Categories:

DRUG RESISTANCE, TYROSINE KINASE

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

RET Gene Symbol

Gene Info:

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

5979 Gene ID

CDHF12 dGene Synonym

CDHR16 dGene Synonym

Gene Info:

Gene Categories:

KINASE, TYROSINE KINASE

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

Gene Info:

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

Gene Info:

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
FDA: RET
- Version: 04-September-2020
Alternate Names:

Gene Info:

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:

Trial Name	Zactima
Novel drug target	Established target
Direct Interaction?	True

Details of the Assay for Interaction	In a biochemical assay.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Notes
Mechanism of Interaction	Tyrosine-protein kinase receptor RET inhibitor
Direct Interaction	yes

Evidence Type	Actionable
Approval Status	Preclinical
Response Type	sensitive

Details of the Assay for Interaction	<i>In vitro</i> inhibition of wild type RET.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Trial Name	ABT-869, Linifanib
Novel drug target	Established target
Specific Action of the Ligand	Inhibition

Details of the Assay for Interaction	In a radiometric biochemical protein kinase assay.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Details of the Assay for Interaction	Assay used apatinib mesylate (YN968D1)
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Trial Name	imatinib mesylate, STI 571,Gleevec, Glivec
Novel drug target	Established target

combination therapy	Cetuximab + Sunitinib
Indication/Tumor Type	olfactory neuroblastoma
Response Type	sensitive

Indication/Tumor Type	thyroid medullary carcinoma
Response Type	sensitive
Approval Status	Phase II

Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive
Approval Status	Phase I

Indication/Tumor Type	non-small cell lung carcinoma
Response Type	predicted – sensitive
Approval Status	Clinical Study

5979	Entrez Gene Id
RET	Gene Symbol
ENSG00000165731	Ensembl Gene Id

PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET PRECURSOR (EC 2.7.1.112) (C-RET). [SOURCE:UNIPROT/SWISSPROT;ACC:P07949]	Description
RET	Display Id
ENSG00000165731	Ensembl Gene Id

ret proto-oncogene	HUGO Gene Name
9967	HUGO Gene ID
RET	Gene Symbol

RET_HUMAN	Uniprot Id
SOLUBLE RET KINASE FRAGMENT	Uniprot Protein Name
ENSG00000165731	Ensembl Gene Id

RET	DrugBank Gene Name
P07949	UniProt Accession
5979	Entrez Gene Id

5979	Entrez Gene Id
RET	MyCancerGenome Gene Symbol
RET	MyCancerGenome Reported Gene Name

ret proto-oncogene	GuideToPharmacology Name
P07949	UniProtKB ID

RET Gene Record

RET 5979 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name Zactima Novel drug target Established target Direct Interaction? True

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction In a biochemical assay. Specific Action of the Ligand Inhibition Endogenous Drug? False

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Notes Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor Direct Interaction yes

Publications: Wilhelm et al., 2011, Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity., Int. J. Cancer

Interaction Types & Directionality: inhibitor (inhibitory)

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

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Evidence Type Actionable Approval Status Preclinical Response Type sensitive

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell line xenograft Response Type predicted – sensitive

Publications: Coxon et al., 2012, Anti-tumor activity of motesanib in a medullary thyroid cancer model., J. Endocrinol. Invest.

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction In a biochemical assay. Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications: Subbiah V et al., 2018, Precision Targeted Therapy with BLU-667 for <i>RET</i>-Driven Cancers., Cancer Discov

Interaction Types & Directionality: inhibitor (inhibitory)

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

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor Indication/Tumor Type non-small cell lung carcinoma

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction <i>In vitro</i> inhibition of wild type RET. Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Notes Trial Name MP-470 Novel drug target Established target

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name ABT-869, Linifanib Novel drug target Established target Specific Action of the Ligand Inhibition

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction In a radiometric biochemical protein kinase assay. Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction? False Endogenous Drug? False 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? False

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor Direct Interaction yes

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction Assay used apatinib mesylate (YN968D1) Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name imatinib mesylate, STI 571,Gleevec, Glivec Novel drug target Established target

Publications: de Groot et al., 2006, Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations., Surgery

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: combination therapy Cetuximab + Sunitinib Indication/Tumor Type olfactory neuroblastoma Response Type sensitive

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

Publications: Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Zactima

Novel drug target Established target

Direct Interaction? True

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a biochemical assay.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Publications:

Wilhelm et al., 2011, Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity., Int. J. Cancer

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type predicted – sensitive

Publications:

Coxon et al., 2012, Anti-tumor activity of motesanib in a medullary thyroid cancer model., J. Endocrinol. Invest.

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a biochemical assay.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Subbiah V et al., 2018, Precision Targeted Therapy with BLU-667 for <i>RET</i>-Driven Cancers., Cancer Discov

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Indication/Tumor Type non-small cell lung carcinoma

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction <i>In vitro</i> inhibition of wild type RET.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Trial Name MP-470

Novel drug target Established target

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name ABT-869, Linifanib

Novel drug target Established target

Specific Action of the Ligand Inhibition

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a radiometric biochemical protein kinase assay.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Assay used apatinib mesylate (YN968D1)

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name imatinib mesylate, STI 571,Gleevec, Glivec

Novel drug target Established target

Publications:

de Groot et al., 2006, Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations., Surgery

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Cetuximab + Sunitinib

Indication/Tumor Type olfactory neuroblastoma

Response Type sensitive

Interaction Types & Directionality:

inhibitor (inhibitory)

Publications:

Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.

Interaction Types & Directionality:

inhibitor (inhibitory)

Publications:

Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.

Interaction Types & Directionality:

inhibitor (inhibitory)

Publications:

Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Interaction Types & Directionality:

substrate

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Phase II

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Phase I

Publications:

Quintela-Fandino et al., 2014, Selective activity over a constitutively active RET-variant of the oral multikinase inhibitor dovitinib: results of the CNIO-BR002 phase I-trial., Mol Oncol

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Approval Status Clinical Study

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Sunitinib

Indication/Tumor Type olfactory neuroblastoma

Response Type sensitive

Publications:

Wang et al., 2016, Recurrent Olfactory Neuroblastoma Treated With Cetuximab and Sunitinib: A Case Report., Medicine (Baltimore)

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Couto et al., 2012, AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer cell lines., PLoS ONE

5979	OncoKB Entrez Id
MTC1	OncoKB Gene Synonym
CDHF12	OncoKB Gene Synonym

Proto-oncogene tyrosine-protein kinase receptor Ret	Gene Name
P07949	UniProt ID

CDHF12	GO Gene Synonym
CDHR16	GO Gene Synonym
PTC	GO Gene Synonym