Target Information
Target General Infomation | |||||
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Target ID |
T91331
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Former ID |
TTDC00131
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Target Name |
FGF-3 receptor
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Gene Name |
FGFR3
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Synonyms |
FGFR-3; CD333; Fibroblast growth factor receptor 3; FGFR3
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Target Type |
Clinical Trial
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Disease | Alzheimer disease [ICD9: 331; ICD10: G30] | ||||
Advanced or metastatic renal cell cancer [ICD9: 189; ICD10: C64] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Hepatocellular carcinoma [ICD9: 155; ICD10: C22.0] | |||||
Multiple myeloma [ICD9: 203; ICD10: C90] | |||||
Retinoblastoma [ICD10: C69.2] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling.
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BioChemical Class |
Kinase
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Target Validation |
T91331
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UniProt ID | |||||
EC Number |
EC 2.7.10.1
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Sequence |
MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELS
CPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLTQRVLCH FSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAG NPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQT YTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVGP DGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAE EELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTVHKISRFPLK RQVSLESNASMSSNTPLVRIARLSSGEGPTLANVSELELPADPKWELSRARLTLGKPLGE GCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIIN LLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQ VARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKW MAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCT HDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSS SSSGDDSVFAHDLLPPAPPSSGGSRT |
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Structure |
1RY7; 2LZL; 4K33
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Drugs and Mode of Action | |||||
Drug(s) | BMS-582664 | Drug Info | Phase 3 | Hepatocellular carcinoma | [522676], [542969] |
E-3810 | Drug Info | Phase 3 | Solid tumours | [524749], [542632] | |
AEE-788 | Drug Info | Phase 1/2 | Solid tumours | [521635], [542626] | |
MK-2461 | Drug Info | Phase 1/2 | Alzheimer disease | [530708] | |
TKI258 | Drug Info | Phase 1/2 | Advanced or metastatic renal cell cancer | [536674], [541242] | |
Anti-FGFR3 | Drug Info | Phase 1 | Multiple myeloma | [550794] | |
PD-0183812 | Drug Info | Terminated | Retinoblastoma | [547217] | |
Inhibitor | 5,11-Dimethyl-6H-pyrido[4,3-b]carbazol-9-ol | Drug Info | [527769] | ||
ACTB-1003 | Drug Info | [543497] | |||
AEE-788 | Drug Info | [536474] | |||
BMS-582664 | Drug Info | [536474] | |||
compound 1d | Drug Info | [531435] | |||
E-3810 | Drug Info | [525382] | |||
MK-2461 | Drug Info | [530708] | |||
PD-0183812 | Drug Info | [525924] | |||
Ro-4396686 | Drug Info | [528018] | |||
SU10991 | Drug Info | [537114] | |||
SU5402 | Drug Info | [537114] | |||
TKI258 | Drug Info | [536474] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
Pathways | |||||
KEGG Pathway | MAPK signaling pathway | ||||
Ras signaling pathway | |||||
Rap1 signaling pathway | |||||
Endocytosis | |||||
PI3K-Akt signaling pathway | |||||
Signaling pathways regulating pluripotency of stem cells | |||||
Regulation of actin cytoskeleton | |||||
Pathways in cancer | |||||
MicroRNAs in cancer | |||||
Bladder cancer | |||||
Central carbon metabolism in cancer | |||||
PANTHER Pathway | FGF signaling pathway | ||||
Reactome | FGFR3 mutant receptor activation | ||||
WikiPathways | Regulation of Actin Cytoskeleton | ||||
Endochondral Ossification | |||||
Bladder Cancer | |||||
Neural Crest Differentiation | |||||
Signaling by FGFR | |||||
References | |||||
Ref 521635 | ClinicalTrials.gov (NCT00107237) AEE788 and Everolimus in Treating Patients With Recurrent or Relapsed Glioblastoma Multiforme. U.S. National Institutes of Health. | ||||
Ref 522676 | ClinicalTrials.gov (NCT00908752) Phase III Trans-Arterial Chemo-Embolization (TACE) Adjuvant HCC. U.S. National Institutes of Health. | ||||
Ref 524749 | ClinicalTrials.gov (NCT02135107) A Double-blind Comparative Study of the Efficacy and Safety of E3810 10mg Once and Twice Daily in Maintenance Therapy for PPI Resistant Gastroesophageal Reflux Disease Patients. U.S. National Institutes of Health. | ||||
Ref 530708 | MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33. | ||||
Ref 536674 | A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin Cancer Res. 2008 Apr 1;14(7):2075-81. | ||||
Ref 541242 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5962). | ||||
Ref 542626 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7643). | ||||
Ref 542632 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7649). | ||||
Ref 542969 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8097). | ||||
Ref 525382 | E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405. doi: 10.1158/0008-5472.CAN-10-2700. Epub 2011 Jan 6. | ||||
Ref 525924 | J Med Chem. 2000 Nov 30;43(24):4606-16.Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. | ||||
Ref 527769 | J Med Chem. 2005 Oct 6;48(20):6194-201.Molecular modeling of wild-type and D816V c-Kit inhibition based on ATP-competitive binding of ellipticine derivatives to tyrosine kinases. | ||||
Ref 528018 | Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3. Epub 2006 Feb 3.Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. | ||||
Ref 530708 | MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33. | ||||
Ref 531435 | In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg Med Chem Lett. 2011 May 15;21(10):2958-61. | ||||
Ref 536474 | A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. |
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