Top ▲

ret proto-oncogene

Click here for help

Target id: 2185

Nomenclature: ret proto-oncogene

Abbreviated Name: Ret

Family: Type XIV RTKs: RET

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1114 10q11.21 RET ret proto-oncogene
Mouse 1 1115 6 55.86 cM Ret ret proto-oncogene
Rat 1 1115 4 q42 Ret ret proto-oncogene
Previous and Unofficial Names Click here for help
cadherin-related family member 16 | CDHF12 | CDHR16 | c-Ret | HSCR1, MEN2A, MTC1, MEN2B | RET51 | RET9
Database Links Click here for help
Alphafold P07949 (Hs), P35546 (Mm)
BRENDA 2.7.10.1
ChEMBL Target CHEMBL2041 (Hs), CHEMBL2034799 (Mm)
DrugBank Target P07949 (Hs)
Ensembl Gene ENSG00000165731 (Hs), ENSMUSG00000030110 (Mm), ENSRNOG00000014751 (Rn)
Entrez Gene 5979 (Hs), 19713 (Mm), 24716 (Rn)
Human Protein Atlas ENSG00000165731 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:5979 (Hs), mmu:19713 (Mm), rno:24716 (Rn)
OMIM 164761 (Hs)
Orphanet ORPHA118274 (Hs)
Pharos P07949 (Hs)
RefSeq Nucleotide NM_020630 (Hs), NM_001080780 (Mm), NM_012643 (Rn)
RefSeq Protein NP_065681 (Hs), NP_001074249 (Mm), NP_036775 (Rn)
UniProtKB P07949 (Hs), P35546 (Mm)
Wikipedia RET (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF NON-PHOSPHORYLATED RET TYROSINE KINASE DOMAIN
PDB Id:  2IVS
Resolution:  2.0Å
Species:  Human
References:  15
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF PHOSPHORYLATED RET TYROSINE KINASE DOMAIN WITH INHIBITOR
PDB Id:  2X2L
Resolution:  2.0Å
Species:  Human
References:  21
Enzyme Reaction Click here for help
EC Number: 2.7.10.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
quizartinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pKd 6
⤷ pKd 8.0 (Kd 9.9x10-9 M) [6]
RG-1530 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pKd 27
⤷ pKd 7.7 (Kd 2.2x10-8 M) [27]
vandetanib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pKd 9
⤷ pKd 7.5 (Kd 3.4x10-8 M) [9]
compound 8h [PMID: 21561767] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.7 pIC50 25
⤷ pIC50 9.7 (IC50 2x10-10 M) [25]
vepafestinib Small molecule or natural product Hs Inhibition 9.7 pIC50 19
⤷ pIC50 9.7 (IC50 2x10-10 M) [19]
Description: Inhibition of peptide substrate phosphorylation by recombinant human RET in the presence of test compound
resencatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.5 pIC50 22
⤷ pIC50 9.5 (IC50 3.4x10-10 M) [22]
Description: Inhibitory potency vs. WT hRET
pralsetinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.4 pIC50 24
⤷ pIC50 9.4 (IC50 4x10-10 M) [24]
Description: In a biochemical assay.
soxataltinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.4 pIC50 23
⤷ pIC50 9.4 (IC50 4x10-10 M) [23]
Description: Inhibition of RET kinase activity in vitro.
compound 1 [PMID: 34917254] Small molecule or natural product Hs Inhibition 9.2 pIC50 17
⤷ pIC50 9.2 (IC50 6.7x10-10 M) [17]
Description: Determined in a biochemical RET kinase activity assay
WF-47-JS03 Small molecule or natural product Hs Inhibition 9.0 – 9.1 pIC50 18
⤷ pIC50 9.1 (IC50 7x10-10 M) [18]
Description: Biochemical inhibition.
pIC50 9.0 (IC50 1x10-9 M) [18]
Description: Inhibition of proliferation of Ba/F3 cells transfected with a RET-Tel fusion gene.
sunitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.8 pIC50 14
⤷ pIC50 8.8 (IC50 1.7x10-9 M) [14]
gilteritinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition ~8.8 pIC50 16
⤷ pIC50 ~8.8 (IC50 ~1.7x10-9 M) [16]
lunbotinib Small molecule or natural product Hs Inhibition 8.2 – 9.0 pIC50 7
⤷ pIC50 9.0 (IC50 1.03x10-9 M) [7]
Description: Inhibition potency for RET V840M mutant
pIC50 8.9 (IC50 1.32x10-9 M) [7]
Description: Inhibition potency for WT RET
pIC50 8.6 (IC50 2.5x10-9 M) [7]
Description: Inhibition potenct for RET-CCDC6 fusion
pIC50 8.2 (IC50 6.54x10-9 M) [7]
Description: Inhibition potency for RET V840L mutant
zeteletinib Small molecule or natural product Hs Inhibition 8.3 pIC50 13
⤷ pIC50 8.3 (IC50 4.6x10-9 M) [13]
tamatinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 8
⤷ pIC50 8.3 (IC50 5x10-9 M) [8]
CEP-11981 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 12
⤷ pIC50 8.3 (IC50 5x10-9 M) [12]
ponatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 20
⤷ pIC50 8.2 (IC50 7x10-9 M) [20]
KBP-7018 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 11
⤷ pIC50 8.1 (IC50 7.6x10-9 M) [11]
cabozantinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.0 pIC50 24
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [24]
Description: In a biochemical assay.
sorafenib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.9 pIC50 14
⤷ pIC50 7.9 (IC50 1.4x10-8 M) [14]
rivoceranib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.9 pIC50 26
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [26]
Description: Assay used apatinib mesylate (YN968D1)
selpercatinib Small molecule or natural product Approved drug Hs Inhibition 7.8 pIC50 4
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [4]
compound 1d [PMID: 21493067] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 29
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [29]
vandetanib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 – 8.4 pIC50 5,24
⤷ pIC50 8.4 (IC50 4x10-9 M) [24]
Description: In a biochemical assay.
pIC50 7.0 (IC50 1x10-7 M) [5]
tafetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 28
⤷ pIC50 7.2 (IC50 6.81x10-8 M) [28]
Description: In a radiometric biochemical protein kinase assay.
lucitanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 pIC50 31
⤷ pIC50 6.7 (IC50 2x10-7 M) [31]
AST-487 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 1
⤷ pIC50 6.1 (IC50 8.8x10-7 M) [1]
Description: In vitro inhibition of wild type RET.
linifanib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.7 pIC50 2
⤷ pIC50 5.7 (IC50 1.9x10-6 M) [2]
Inhibitor Comments
Note that sorafenib is a multi-target kinase inhibitor. Kinase targets include PDGFRβ, BRAF, RAF, KIT, FLT3 and VEGF receptors.
Sunitinib inhibits a range of additional kinases, including platelet-derived growth factor receptora α and β (PDGFRα, PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3) and colony stimulating factor receptor Type 1 (CSF-1R).
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 9,30
Key to terms and symbols Click column headers to sort
Target used in screen: RET
Ligand Sp. Type Action Value Parameter
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.4 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 8.2 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.0 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
motesanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
Target used in screen: RET(M918T)
Ligand Sp. Type Action Value Parameter
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.2 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.4 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.4 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.2 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 8.1 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
Target used in screen: RET(V804L)
Ligand Sp. Type Action Value Parameter
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.9 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.7 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.4 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.7 pKd
Target used in screen: RET(V804M)
Ligand Sp. Type Action Value Parameter
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 9.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.5 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.3 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
quizartinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.8 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 3,10
Key to terms and symbols Click column headers to sort
Target used in screen: Ret/RET
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
TWS119 Small molecule or natural product Hs Inhibitor Inhibition -0.2 2.0 0.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 0.1 1.0 0.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.5 -1.0 1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.6 3.5 6.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 1.2 2.0 -1.0
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 1.8
Syk inhibitor Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 1.9 1.0 1.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 2.4
K-252a Small molecule or natural product Hs Inhibitor Inhibition 2.4 2.0 1.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.5 -1.0 -1.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune system development
Immuno Process:  Chemotaxis & migration
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Mrgprdtm1Mjz|Rettm1Ddg|Tg(Wnt1-cre)11Rth Mrgprdtm1Mjz/?,Rettm1Ddg/Rettm1Ddg,Tg(Wnt1-cre)11Rth/0
involves: 129 * 129S1/Sv * C57BL/6 * C57BL/6J * CBA/J		 MGI:2447280  MGI:3033142  MGI:97902  MP:0008415 abnormal neurite morphology PMID: 17553423 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Bilateral renal dysplasia
Orphanet: ORPHA93173
Disease:  Central hypoventilation syndrome, congenital; CCHS
Synonyms: Haddad syndrome [Orphanet: ORPHA99803]
Ondine-Hirschsprung disease
OMIM: 209880
Orphanet: ORPHA99803
Disease:  Hirschsprung disease, susceptibility to, 1; HSCR1
Synonyms: Hirschsprung disease [Orphanet: ORPHA388]
OMIM: 142623
Orphanet: ORPHA388
Disease:  Multiple endocrine neoplasia IIA
Synonyms: Multiple endocrine neoplasia [Disease Ontology: DOID:3125]
Disease Ontology: DOID:3125
OMIM: 171400
Orphanet: ORPHA247698
Disease:  Multiple endocrine neoplasia IIB
Synonyms: Multiple endocrine neoplasia [Disease Ontology: DOID:3125]
Disease Ontology: DOID:3125
OMIM: 162300
Orphanet: ORPHA247709
Disease:  Pheochromocytoma
OMIM: 171300
Disease:  Renal agenesis
Disease Ontology: DOID:14766
OMIM: 191830
Orphanet: ORPHA1848
Disease:  Thyroid carcinoma, familial medullary
Synonyms: Familial medullary thyroid carcinoma [Disease Ontology: DOID:0050547]
Disease Ontology: DOID:0050547
OMIM: 155240
Orphanet: ORPHA99361
Disease:  Thyroid carcinoma, papillary
Synonyms: Differentiated thyroid carcinoma [Orphanet: ORPHA146]
Papillary thyroid carcinoma [Disease Ontology: DOID:3969]
Disease Ontology: DOID:3969
OMIM: 188550
Orphanet: ORPHA146
Disease:  Unilateral renal dysplasia
Orphanet: ORPHA93172

References

Show »

1. Akeno-Stuart N, Croyle M, Knauf JA, Malaguarnera R, Vitagliano D, Santoro M, Stephan C, Grosios K, Wartmann M, Cozens R et al.. (2007) The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res, 67 (14): 6956-64. [PMID:17638907]

2. Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, Li J, Guo J, Bousquet PF, Ghoreishi-Haack NS et al.. (2006) Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther, 5 (4): 995-1006. [PMID:16648571]

3. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

4. Andrews SW, Aronow S, Blake JF, Brandhuber BJ, Cook A, Hass J, Jiang Y, Kolakowski GR, McFaddin EA, McKenney M et al.. (2018) Substituted pyrazolo[1,5-a]pyridine compounds as ret kinase inhibitors. Patent number: WO2018071447A1. Assignee: Loxo Oncology. Priority date: 10/10/2016. Publication date: 19/04/2018.

5. Carlomagno F, Vitagliano D, Guida T, Ciardiello F, Tortora G, Vecchio G, Ryan AJ, Fontanini G, Fusco A, Santoro M. (2002) ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res, 62 (24): 7284-90. [PMID:12499271]

6. Chao Q, Sprankle KG, Grotzfeld RM, Lai AG, Carter TA, Velasco AM, Gunawardane RN, Cramer MD, Gardner MF, James J et al.. (2009) Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor. J Med Chem, 52 (23): 7808-16. [PMID:19754199]

7. Chen Z, Duan S, Li G, Han R, Sun Q, Jing L, Han X, Tian Q, Song H, Xue T et al.. (2020) Heterocyclic compound, pharmaceutical composition comprising same, preparation method therefor, and use thereof. Patent number: WO2020168939A1. Assignee: Sichuan Kelun Biotech Biopharmaceutical Co. Priority date: 11/02/2020. Publication date: 27/08/2020.

8. Clemens GR, Schroeder RE, Magness SH, Weaver EV, Lech JW, Taylor VC, Masuda ES, Baluom M, Grossbard EB. (2009) Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing. Birth Defects Res Part A Clin Mol Teratol, 85 (2): 130-6. [PMID:19107952]

9. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

10. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

11. Huang Z, Li H, Zhang Q, Lu F, Hong M, Zhang Z, Guo X, Zhu Y, Li S, Liu H. (2017) Discovery of Indolinone-Based Multikinase Inhibitors as Potential Therapeutics for Idiopathic Pulmonary Fibrosis. ACS Med Chem Lett, 8 (11): 1142-1147. [PMID:29152045]

12. Hudkins RL, Becknell NC, Zulli AL, Underiner TL, Angeles TS, Aimone LD, Albom MS, Chang H, Miknyoczki SJ, Hunter K et al.. (2012) Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent. J Med Chem, 55 (2): 903-13. [PMID:22148921]

13. Inagaki H, Shibata Y, Namiki H, Kageji H, Nakayama K, Kaneta Y. (2018) Pyridine compound. Patent number: WO2018060714A1. Assignee: Daiichi Sankyo Company. Priority date: 29/09/2016. Publication date: 05/04/2018.

14. Kitagawa D, Yokota K, Gouda M, Narumi Y, Ohmoto H, Nishiwaki E, Akita K, Kirii Y. (2013) Activity-based kinase profiling of approved tyrosine kinase inhibitors. Genes Cells, 18 (2): 110-22. [PMID:23279183]

15. Knowles PP, Murray-Rust J, Kjaer S, Scott RP, Hanrahan S, Santoro M, Ibáñez CF, McDonald NQ. (2006) Structure and chemical inhibition of the RET tyrosine kinase domain. J Biol Chem, 281 (44): 33577-87. [PMID:16928683]

16. Lee LY, Hernandez D, Rajkhowa T, Smith SC, Raman JR, Nguyen B, Small D, Levis M. (2017) Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor. Blood, 129 (2): 257-260. [PMID:27908881]

17. Mathison CJN, Yang Y, Nelson J, Huang Z, Jiang J, Chianelli D, Rucker PV, Roland J, Xie YF, Epple R et al.. (2021) Antitarget Selectivity and Tolerability of Novel Pyrrolo[2,3-d]pyrimidine RET Inhibitors. ACS Med Chem Lett, 12 (12): 1912-1919. [PMID:34917254]

18. Mathison CNJ, Chianelli D, Ruckler PV, Nelson J, Roland J, Huang Z, Yang Y, Jiang J, Xie YF, Epple R et al.. (2020) Efficacy and Tolerability of Pyrazolo[1,5-a]pyrimidine RET Kinase Inhibitors for the Treatment of Lung Adenocarcinoma. ACS Med Chem Lett, [Articles ASAP]. DOI: 10.1021/acsmedchemlett.0c00015

19. Miyazaki I, Shimamura T, Kato M, Fujita H, Iguchi S. (2018) Novel fused pyrimidine compound or salt thereof. Patent number: US20180009818A1. Assignee: Taiho Pharmaceutical Co Ltd. Priority date: 23/01/2016. Publication date: 11/01/2018.

20. Mologni L, Redaelli S, Morandi A, Plaza-Menacho I, Gambacorti-Passerini C. (2013) Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase. Mol Cell Endocrinol, 377 (1-2): 1-6. [PMID:23811235]

21. Mologni L, Rostagno R, Brussolo S, Knowles PP, Kjaer S, Murray-Rust J, Rosso E, Zambon A, Scapozza L, McDonald NQ et al.. (2010) Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorg Med Chem, 18 (4): 1482-96. [PMID:20117004]

22. Su Y, Wang J, Bao R. (2020) Inhibitor containing bicyclic derivative, preparation method therefor and use thereof. Patent number: WO2020228756A1. Assignee: Shanghai Hansoh Biomedical Technology Co., Ltd., Jiangsu Hansoh Pharmaceutical Group Co., Ltd.. Priority date: 14/05/2020. Publication date: 19/11/2020.

23. Su Y, Wang J, Bao R. (2020) Inhibitor containing bicyclic derivative, preparation method therefor and use thereof. Patent number: WO2020228756A1. Assignee: Shanghai Hansoh Biomedical Technology Co., Ltd., Jiangsu Hansoh Pharmaceutical Group Co., Ltd.. Priority date: 14/05/2020. Publication date: 19/11/2020.

24. Subbiah V, Gainor JF, Rahal R, Brubaker JD, Kim JL, Maynard M, Hu W, Cao Q, Sheets MP, Wilson D et al.. (2018) Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov, 8 (7): 836-849. [PMID:29657135]

25. Thomas M, Huang WS, Wen D, Zhu X, Wang Y, Metcalf CA, Liu S, Chen I, Romero J, Zou D et al.. (2011) Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett, 21 (12): 3743-8. [PMID:21561767]

26. Tian S, Quan H, Xie C, Guo H, Lü F, Xu Y, Li J, Lou L. (2011) YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci, 102 (7): 1374-80. [PMID:21443688]

27. Tovar C, Higgins B, Deo D, Kolinsky K, Liu JJ, Heimbrook DC, Vassilev LT. (2010) Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapy. Cell Cycle, 9 (16): 3364-75. [PMID:20814247]

28. Wang D, Tang F, Wang S, Jiang Z, Zhang L. (2012) Preclinical anti-angiogenesis and anti-tumor activity of SIM010603, an oral, multi-targets receptor tyrosine kinases inhibitor. Cancer Chemother Pharmacol, 69 (1): 173-83. [PMID:21638122]

29. Wang T, Ioannidis S, Almeida L, Block MH, Davies AM, Lamb ML, Scott DA, Su M, Zhang HJ, Alimzhanov M et al.. (2011) In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg Med Chem Lett, 21 (10): 2958-61. [PMID:21493067]

30. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

31. Zhou Y, Chen Y, Tong L, Xie H, Wen W, Zhang J, Xi Y, Shen Y, Geng M, Wang Y et al.. (2012) AL3810, a multi-tyrosine kinase inhibitor, exhibits potent anti-angiogenic and anti-tumour activity via targeting VEGFR, FGFR and PDGFR. J Cell Mol Med, 16 (10): 2321-30. [PMID:22304225]

How to cite this page

Type XIV RTKs: RET: ret proto-oncogene. Last modified on 14/08/2024. Accessed on 07/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2185.