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
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
42
PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET
Proto-oncogene c-Ret
Cadherin family member 12
Extracellular cell-membrane anchored RET cadherin 120 kDa fragment
PA34335
T60631

Gene Info:

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
Target Subclass	Kinase
Target Main Class	Receptors
Target Subclass	Other
Transmembrane Helix Count	1
Gene Biotype	PROTEIN_CODING

(25 More Sources)

Gene Categories: Category Details

KINASE
TYROSINE KINASE
DRUG RESISTANCE
DRUGGABLE GENOME
CLINICALLY ACTIONABLE

Publications:

Frisk et al., 2001, CGH alterations in medullary thyroid carcinomas in relation to the RET M918T mutation and clinical outcome., Int. J. Oncol.
Carlomagno et al., 2009, Identification of tyrosine 806 as a molecular determinant of RET kinase sensitivity to ZD6474., Endocr. Relat. Cancer
Lam et al., 2010, Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer., J. Clin. Oncol.
Kloos et al., 2009, Phase II trial of sorafenib in metastatic thyroid cancer., J. Clin. Oncol.
Gupta-Abramson et al., 2008, Phase II trial of sorafenib in advanced thyroid cancer., J. Clin. Oncol.
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.
Wilson et al., 1976, Some properties of the redox components of cytochrome c oxidase and their interactions., Arch. Biochem. Biophys.
Sherman, 2011, Targeted therapies for thyroid tumors., Mod. Pathol.
Drilon et al., 2013, Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas., Cancer Discov
Renaud et al., 1975, Effects of 5,6-dihydroxytryptamine on tyrosine-hydroxylase activity in central catecholaminergic neurons of the rat., Biochem. Pharmacol.
Santoro et al., 1998, Molecular biology of the MEN2 gene., J. Intern. Med.
Ehmann F et al., 2014, European Medicines Agency initiatives and perspectives on pharmacogenomics., Br J Clin Pharmacol
Couto et al., 2012, AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer cell lines., PLoS ONE
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
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.
Kato et al., 2017, RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients., Clin. Cancer Res.
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.
Coxon et al., 2012, Anti-tumor activity of motesanib in a medullary thyroid cancer model., J. Endocrinol. Invest.
Gautschi et al., 2013, A patient with lung adenocarcinoma and RET fusion treated with vandetanib., J Thorac Oncol
Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
Dabir et al., 2014, RET mutation and expression in small-cell lung cancer., J Thorac Oncol
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
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.
Carlomagno et al., 2004, Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors., Oncogene
Vitagliano et al., 2011, The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells., Endocr. Relat. Cancer
Gautschi et al., 2017, Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry., J. Clin. Oncol.
Egawa et al., 1998, Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan., Jpn. 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.
Verbeek et al., 2011, The effects of four different tyrosine kinase inhibitors on medullary and papillary thyroid cancer cells., J. Clin. Endocrinol. Metab.
Hatem et al., 2016, Vandetanib as a potential new treatment for estrogen receptor-negative breast cancers., Int. J. Cancer
Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.
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
Gild et al., 2013, Targeting mTOR in RET mutant medullary and differentiated thyroid cancer cells., Endocr. Relat. Cancer
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.
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
Huang et al., 2016, Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma., Mol. Cancer Ther.
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
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.
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.
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.
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.

CEP-32496 RET

Interaction Score: 1.99

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

PMIDs:
29538669 28011461

Sources:
JAX-CKB ChemblInteractions CIViC TTD
PRALSETINIB RET

Interaction Score: 1.99

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
TTD OncoKB
CABOZANTINIB RET

Interaction Score: 1.35

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Notes

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

PMIDs:
27825636 27525386 21606412 23705946 28447912 17 8007 2015 25366691 23584301 23533264

Sources:
PharmGKB MyCancerGenomeClinicalTrial MyCancerGenome TALC JAX-CKB FDA OncoKB CIViC
VANDETANIB RET

Interaction Score: 0.83

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Zactima

Novel drug target Established target

Notes

PMIDs:
11351254 19029224 20368568 19255327 18541894 25366691 8007 21455200 23533264 17 9681850 24433361 23056499 27825616 22025146 20065189 27683183 27803005 21422803 23584301 10592235 25122427 25157968 20847059 15184865 20943719 28447912 9839497 18073307 21470995 26686064 2015

Sources:
DTC TdgClinicalTrial TTD TALC ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions MyCancerGenome PharmGKB DoCM MyCancerGenomeClinicalTrial OncoKB CIViC
SUNITINIB RET

Interaction Score: 0.77

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Cetuximab + Sunitinib

Indication/Tumor Type olfactory neuroblastoma

Response Type sensitive

PMIDs:
16849418 28447912 27149458 19248971 20696054 18541894 9681850 9839497 20847059 19255327 18073307 21455200 20368568 11351254 21422803 21470995 20943719 23056499 22025146 20065189 25157968

Sources:
NCI JAX-CKB TdgClinicalTrial PharmGKB DoCM TALC TEND MyCancerGenome CIViC
MOTESANIB RET

Interaction Score: 0.75

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type predicted – sensitive

PMIDs:
21422803

Sources:
TALC MyCancerGenome JAX-CKB ChemblInteractions CIViC
ALECTINIB HYDROCHLORIDE RET

Interaction Score: 0.5

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
SITRAVATINIB RET

Interaction Score: 0.5

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
LENVATINIB RET

Interaction Score: 0.5

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

PMIDs:
25295214 27496134 17943726

Sources:
TALC JAX-CKB CIViC
ALECTINIB RET

Interaction Score: 0.43

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Approval Status Clinical Study

PMIDs:
27544060

Sources:
JAX-CKB CIViC
AMUVATINIB RET

Interaction Score: 0.43

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Trial Name MP-470

Novel drug target Established target

PMIDs:
None found

Sources:
TALC MyCancerGenome TdgClinicalTrial
PONATINIB RET

Interaction Score: 0.41

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

PMIDs:
25122427 23526464 23811235 27496134

Sources:
TALC JAX-CKB CIViC MyCancerGenomeClinicalTrial TTD
AZD-1480 RET

Interaction Score: 0.4

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
23056499

Sources:
JAX-CKB
REGORAFENIB RET

Interaction Score: 0.25

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
21170960

Sources:
TALC MyCancerGenome JAX-CKB ChemblInteractions MyCancerGenomeClinicalTrial TTD
IMATINIB MESYLATE RET

Interaction Score: 0.2

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
12490842

Sources:
NCI
TANESPIMYCIN RET

Interaction Score: 0.17

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15302866

Sources:
NCI
SORAFENIB RET

Interaction Score: 0.15

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type predicted – sensitive

Approval Status Phase II

PMIDs:
28362716 16507829 15466206 17016424 20368568 18849971 17664273

Sources:
DTC MyCancerGenome JAX-CKB CIViC PharmGKB
ROMIPLOSTIM RET

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
AST-487 RET

Interaction Score: 0.11

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
23828865

Sources:
DTC ChemblInteractions CIViC
SUNITINIB MALATE RET

Interaction Score: 0.11

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
QUIZARTINIB RET

Interaction Score: 0.11

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
BARASERTIB RET

Interaction Score: 0.11

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LESTAURTINIB RET

Interaction Score: 0.1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

PMIDs:
None found

Sources:
ChemblInteractions
SAPANISERTIB RET

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23828865

Sources:
CIViC
AT-9283 RET

Interaction Score: 0.09

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

PMIDs:
None found

Sources:
TALC
EVEROLIMUS RET

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Phase II

PMIDs:
27683183 26294908

Sources:
JAX-CKB
SORAFENIB TOSYLATE RET

Interaction Score: 0.06

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
CEP-2563 RET

Interaction Score: 0.06

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
CHEMBL202721 RET

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
IMATINIB RET

Interaction Score: 0.05

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name imatinib mesylate, STI 571,Gleevec, Glivec

Novel drug target Established target

PMIDs:
16782438

Sources:
TdgClinicalTrial TEND
CETUXIMAB RET

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Sunitinib

Indication/Tumor Type olfactory neuroblastoma

Response Type sensitive

PMIDs:
27149458

Sources:
JAX-CKB
DOVITINIB RET

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Phase I

PMIDs:
25103625

Sources:
DTC ClearityFoundationClinicalTrial JAX-CKB
AZD-1152-HQPA RET

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
ENMD-2076 RET

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name ENMD-2076

Novel drug target Established target

PMIDs:
None found

Sources:
TdgClinicalTrial
GENISTEIN RET

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
12490842

Sources:
NCI
LAPATINIB RET

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
SB-220025 RET

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CHEMBL546797 RET

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LINIFANIB RET

Interaction Score: 0.03

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name ABT-869, Linifanib

Novel drug target Established target

PMIDs:
None found

Sources:
DTC TdgClinicalTrial
TOZASERTIB RET

Interaction Score: 0.03

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
19035792

Sources:
DTC
HESPERADIN RET

Interaction Score: 0.02

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
19035792

Sources:
DTC
PAZOPANIB RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
DEXAMETHASONE RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10947080

Sources:
NCI
ALISERTIB RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CHEMBL1997335 RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
SNS-314 RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
OSI-632 RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
PALBOCICLIB RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CEDIRANIB RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
ERLOTINIB RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
JNJ-7706621 RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
PD-0166285 RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
ENTRECTINIB RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
GW441756X RET

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
R-406 RET

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RG-1530 RET

Interaction Score: 0.01

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
DTC
SP-600125 RET

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CYC-116 RET

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
TAE-684 RET

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
ILORASERTIB RET

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
PF-00562271 RET

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CENISERTIB RET

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC

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:
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:

JAX-CKB: RET

Version: 27-September-2017

Alternate Names:

5979 CKB Entrez Id

RET CKB Gene Synonym

CDHF12 CKB Gene Synonym

Gene Info:

Publications:

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

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

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

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

CIViC: RET

Version: 14-September-2020

Alternate Names:

5979 Entrez Gene ID

42 CIViC Gene ID

Gene Info:

Gene Categories:

DRUG RESISTANCE

Publications:

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

Drilon A et al., 2020, Efficacy of Selpercatinib in <i>RET</i> Fusion-Positive Non-Small-Cell Lung Cancer., N Engl J Med

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

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:

Frisk et al., 2001, CGH alterations in medullary thyroid carcinomas in relation to the RET M918T mutation and clinical outcome., Int. J. Oncol.

Lam et al., 2010, Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer., J. Clin. Oncol.

Kloos et al., 2009, Phase II trial of sorafenib in metastatic thyroid cancer., 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

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

5979 OncoKB Entrez Id

MTC1 OncoKB Gene Synonym

CDHF12 OncoKB Gene Synonym

Gene Info:

Publications:
GO: RET
- Version: 01-February-2022
Alternate Names:

CDHF12 GO Gene Synonym

CDHR16 GO Gene Synonym

PTC GO Gene Synonym

Gene Info:

Gene Categories:

TYROSINE KINASE

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

RET Gene Symbol

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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:
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: 01-February-2022
Alternate Names:

Proto-oncogene tyrosine-protein kinase receptor Ret Gene Name

P07949 UniProt ID

Gene Info:

Gene Categories:

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:

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

Notes
Indication/Tumor Type	thyroid medullary carcinoma
Response Type	sensitive

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

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

Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive
Approval Status	Preclinical

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

Trial Name	ABT-869, Linifanib
Novel drug target	Established target

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

antagonist (inhibitory)
inhibitor (inhibitory)

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

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

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

Proto-oncogene tyrosine-protein kinase receptor Ret	Gene Name
P07949	UniProt 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: Direct Interaction yes Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor Indication/Tumor Type non-small cell lung carcinoma

PMIDs: 29538669 28011461

Sources: JAX-CKB ChemblInteractions CIViC TTD

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Sources: TTD OncoKB

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

Interaction Info: Notes Indication/Tumor Type thyroid medullary carcinoma Response Type sensitive

PMIDs: 27825636 27525386 21606412 23705946 28447912 17 8007 2015 25366691 23584301 23533264

Sources: PharmGKB MyCancerGenomeClinicalTrial MyCancerGenome TALC JAX-CKB FDA OncoKB CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name Zactima Novel drug target Established target Notes

PMIDs: 11351254 19029224 20368568 19255327 18541894 25366691 8007 21455200 23533264 17 9681850 24433361 23056499 27825616 22025146 20065189 27683183 27803005 21422803 23584301 10592235 25122427 25157968 20847059 15184865 20943719 28447912 9839497 18073307 21470995 26686064 2015

Sources: DTC TdgClinicalTrial TTD TALC ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions MyCancerGenome PharmGKB DoCM MyCancerGenomeClinicalTrial OncoKB CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 16849418 28447912 27149458 19248971 20696054 18541894 9681850 9839497 20847059 19255327 18073307 21455200 20368568 11351254 21422803 21470995 20943719 23056499 22025146 20065189 25157968

Sources: NCI JAX-CKB TdgClinicalTrial PharmGKB DoCM TALC TEND MyCancerGenome CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 21422803

Sources: TALC MyCancerGenome JAX-CKB ChemblInteractions CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: TTD

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 25295214 27496134 17943726

Sources: TALC JAX-CKB CIViC

Interaction Types & Directionality: n/a

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

PMIDs: 27544060

Sources: JAX-CKB CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: None found

Sources: TALC MyCancerGenome TdgClinicalTrial

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type Advanced Solid Tumor Response Type sensitive Approval Status Preclinical

PMIDs: 25122427 23526464 23811235 27496134

Sources: TALC JAX-CKB CIViC MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type thyroid medullary carcinoma Response Type sensitive Approval Status Preclinical - Cell culture

PMIDs: 23056499

Sources: JAX-CKB

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 21170960

Sources: TALC MyCancerGenome JAX-CKB ChemblInteractions MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 12490842

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 15302866

Sources: NCI

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type thyroid medullary carcinoma Response Type predicted – sensitive Approval Status Phase II

PMIDs: 28362716 16507829 15466206 17016424 20368568 18849971 17664273

Sources: DTC MyCancerGenome JAX-CKB CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: TTD

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

Indication/Tumor Type non-small cell lung carcinoma

PMIDs:
29538669 28011461

Sources:
JAX-CKB ChemblInteractions CIViC TTD

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
None found

Sources:
TTD OncoKB

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Notes

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

PMIDs:
27825636 27525386 21606412 23705946 28447912 17 8007 2015 25366691 23584301 23533264

Sources:
PharmGKB MyCancerGenomeClinicalTrial MyCancerGenome TALC JAX-CKB FDA OncoKB CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Zactima

Novel drug target Established target

Notes

PMIDs:
11351254 19029224 20368568 19255327 18541894 25366691 8007 21455200 23533264 17 9681850 24433361 23056499 27825616 22025146 20065189 27683183 27803005 21422803 23584301 10592235 25122427 25157968 20847059 15184865 20943719 28447912 9839497 18073307 21470995 26686064 2015

Sources:
DTC TdgClinicalTrial TTD TALC ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions MyCancerGenome PharmGKB DoCM MyCancerGenomeClinicalTrial OncoKB CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

combination therapy Cetuximab + Sunitinib

Indication/Tumor Type olfactory neuroblastoma

Response Type sensitive

PMIDs:
16849418 28447912 27149458 19248971 20696054 18541894 9681850 9839497 20847059 19255327 18073307 21455200 20368568 11351254 21422803 21470995 20943719 23056499 22025146 20065189 25157968

Sources:
NCI JAX-CKB TdgClinicalTrial PharmGKB DoCM TALC TEND MyCancerGenome CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type predicted – sensitive

PMIDs:
21422803

Sources:
TALC MyCancerGenome JAX-CKB ChemblInteractions CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
TTD

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

PMIDs:
25295214 27496134 17943726

Sources:
TALC JAX-CKB CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type predicted – sensitive

Approval Status Clinical Study

PMIDs:
27544060

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Trial Name MP-470

Novel drug target Established target

PMIDs:
None found

Sources:
TALC MyCancerGenome TdgClinicalTrial

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

PMIDs:
25122427 23526464 23811235 27496134

Sources:
TALC JAX-CKB CIViC MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
23056499

Sources:
JAX-CKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
21170960

Sources:
TALC MyCancerGenome JAX-CKB ChemblInteractions MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality:

n/a

PMIDs:
12490842

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
15302866

Sources:
NCI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type thyroid medullary carcinoma

Response Type predicted – sensitive

Approval Status Phase II

PMIDs:
28362716 16507829 15466206 17016424 20368568 18849971 17664273

Sources:
DTC MyCancerGenome JAX-CKB CIViC PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
TTD

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
23828865

Sources:
DTC ChemblInteractions CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

n/a