Target Information

Target General Infomation
Target ID
T47101 (Former ID: TTDC00024)
Target Name
Fibroblast growth factor receptor 1 (FGFR1)
Synonyms
c-fgr; bFGF-R-1; bFGF-R; N-sam; HBGFR; Fms-like tyrosine kinase 2; FLT2; FLT-2; FLG; FGFR-1; FGFBR; CEK; CD331 antigen; CD331; Basic fibroblast growth factor receptor 1; BFGFR
Gene Name
FGFR1
Target Type
Successful target
 [1]
Disease [+] 3 Target-related Diseases +
1 Colorectal cancer [ICD-11: 2B91]
2 Idiopathic interstitial pneumonitis [ICD-11: CB03]
3 Thrombocytopenia [ICD-11: 3B64]
Function
Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation. Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
BioChemical Class
Kinase
UniProt ID
FGFR1_HUMAN
EC Number
EC 2.7.10.1
Sequence
MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDD
VQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSD
ALPSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPS
SGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSIN
HTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKI
GPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLE
ALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKS
IPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRDRLVL
GKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGK
HKNIINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGLEYCYNPSHNPEEQLSSKDL
VSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNG
RLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMD
KPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSF
PDTRSSTCSSGEDSVFSHEPLPEEPCLPRHPAQLANGGLKRR
Drugs and Modes of Action
Approved Drug(s) [+] 2 Approved Drugs +
1 Intedanib Drug Info Approved Colorectal cancer [2]
2 Romiplostim Drug Info Approved Thrombocytopenia [3], [4]
Clinical Trial Drug(s) [+] 15 Clinical Trial Drugs +
1 ARQ-087 Drug Info Phase 3 Intrahepatic cholangiocarcinoma [5]
2 E-3810 Drug Info Phase 3 Solid tumour/cancer [6], [7]
3 Rosiglitazone + metformin Drug Info Phase 3 Diabetic complication [8]
4 AZD4547 Drug Info Phase 2/3 Solid tumour/cancer [9], [10]
5 AM-001 Drug Info Phase 2 Dermatological disease [11]
6 BGJ398 Drug Info Phase 2 Solid tumour/cancer [12], [13]
7 FGF-1 Drug Info Phase 2 Coronary heart disease [14]
8 FP-1039 Drug Info Phase 2 Endometrial cancer [15]
9 INCB54828 Drug Info Phase 2 Bladder cancer [5]
10 Debio 1347 Drug Info Phase 1/2 Breast cancer [5]
11 JNJ-42756493 Drug Info Phase 1/2 Lymphoma [16]
12 MK-2461 Drug Info Phase 1/2 Alzheimer disease [17]
13 KW-2449 Drug Info Phase 1 Acute myeloid leukaemia [18], [19]
14 NGM313 Drug Info Phase 1 Type-2 diabetes [20]
15 Sulfatinib Drug Info Phase 1 Solid tumour/cancer [21]
Preclinical Drug(s) [+] 1 Preclinical Drugs +
1 BMS-695735 Drug Info Preclinical Solid tumour/cancer [22]
Discontinued Drug(s) [+] 1 Discontinued Drugs +
1 PD-0183812 Drug Info Terminated Retinoblastoma [23]
Mode of Action [+] 5 Modes of Action +
Modulator [+] 6 Modulator drugs +
1 Intedanib Drug Info [2]
2 AZD4547 Drug Info [27]
3 BGJ398 Drug Info [30]
4 JNJ-42756493 Drug Info [29]
5 NGM313 Drug Info [20]
6 3052230 Drug Info [39]
Inhibitor [+] 27 Inhibitor drugs +
1 Romiplostim Drug Info [1]
2 E-3810 Drug Info [24]
3 Rosiglitazone + metformin Drug Info [25], [26]
4 ARQ-087 Drug Info [29]
5 INCB54828 Drug Info [5]
6 Debio 1347 Drug Info [5]
7 MK-2461 Drug Info [17]
8 Sulfatinib Drug Info [33]
9 BMS-695735 Drug Info [34]
10 PD-0183812 Drug Info [35]
11 2-(1H-indazol-3-yl)-1H-benzo[d]imidazole Drug Info [36]
12 3-(3-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine Drug Info [37]
13 3-Benzimidazol-2-ylhydroquinolin-2-one Drug Info [38]
14 AAL-993 Drug Info [1]
15 ACTB-1003 Drug Info [29]
16 HKI-9924129 Drug Info [40]
17 NP-506 Drug Info [41]
18 PD-0166326 Drug Info [40]
19 PD-0173952 Drug Info [40]
20 PD-0173955 Drug Info [40]
21 PD-0173956 Drug Info [40]
22 PD-0173958 Drug Info [40]
23 PD-0179483 Drug Info [40]
24 PMID22765894C8h Drug Info [42]
25 PMID24900538C2c Drug Info [43]
26 PMID26080733C7r Drug Info [44]
27 Ro-4396686 Drug Info [45]
Antagonist [+] 2 Antagonist drugs +
1 AM-001 Drug Info [28]
2 FP-1039 Drug Info [32]
Binder [+] 1 Binder drugs +
1 FGF-1 Drug Info [31]
Agonist [+] 1 Agonist drugs +
1 SAR-106881 Drug Info [29]
Target Regulators
Target-regulating microRNAs
Target-regulating microRNAs Info 
Target-interacting Proteins
Target-interacting Proteins Info 
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Expression Profile Info 
Drug Resistance
 Mutation (DRM)
Drug Resistance Mutation Info 
Target Affiliated Biological Pathways
KEGG Pathway [+] 12 KEGG Pathways +
1 MAPK signaling pathway
2 Ras signaling pathway
3 Rap1 signaling pathway
4 PI3K-Akt signaling pathway
5 Adherens junction
6 Signaling pathways regulating pluripotency of stem cells
7 Regulation of actin cytoskeleton
8 Pathways in cancer
9 Proteoglycans in cancer
10 Prostate cancer
11 Melanoma
12 Central carbon metabolism in cancer
NetPath Pathway [+] 1 NetPath Pathways +
1 TCR Signaling Pathway
Panther Pathway [+] 2 Panther Pathways +
1 Angiogenesis
2 FGF signaling pathway
PID Pathway [+] 4 PID Pathways +
1 Glypican 1 network
2 Syndecan-4-mediated signaling events
3 N-cadherin signaling events
4 FGF signaling pathway
WikiPathways [+] 9 WikiPathways +
1 Regulation of Actin Cytoskeleton
2 Endochondral Ossification
3 MAPK Signaling Pathway
4 Mesodermal Commitment Pathway
5 Hair Follicle Development: Induction (Part 1 of 3)
6 Integrated Pancreatic Cancer Pathway
7 Signaling Pathways in Glioblastoma
8 Neural Crest Differentiation
9 Signaling by FGFR
Target-Related Models and Studies
Target Validation
Target Validation Info 
Target QSAR Model
Target QSAR Model 
References
REF 1 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
REF 2 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
REF 3 URL: 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: 6974).
REF 4 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
REF 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 6 URL: 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 7 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 8 ClinicalTrials.gov (NCT00499707) Efficacy and Safety Study of Rosiglitazone/Metformin Therapy vs Rosiglitazone and Metformin in Type 2 Diabetes Subjects. U.S. National Institutes of Health.
REF 9 URL: 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: 7707).
REF 10 ClinicalTrials.gov (NCT02154490) Lung-MAP: S1400 Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IIIB-IV Squamous Cell Lung Cancer. U.S. National Institutes of Health.
REF 11 ClinicalTrials.gov (NCT01938599) Study Comparing AM001 Cream to Vehicle in the Treatment of Plaque Psoriasis. U.S. National Institutes of Health.
REF 12 URL: 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: 7877).
REF 13 ClinicalTrials.gov (NCT02160041) BGJ398 for Patients With Tumors With FGFR Genetic Alterations. U.S. National Institutes of Health.
REF 14 URL: 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: 4923).
REF 15 ClinicalTrials.gov (NCT01244438) Study of FP-1039 in Subjects With Endometrial Cancers. U.S. National Institutes of Health.
REF 16 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036975)
REF 17 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
REF 18 URL: 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: 5691).
REF 19 KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
REF 20 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 21 ClinicalTrials.gov (NCT02133157) Phase I Study of Sulfatinib(HMPL-012) in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
REF 22 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022289)
REF 23 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014130)
REF 24 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.
REF 25 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.
REF 26 Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies. Clin Cancer Res. 2005 Sep 1;11(17):6240-6.
REF 27 AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 2012 Apr 15;72(8):2045-56.
REF 28 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029917)
REF 29 URL: 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. (Target id: 1808).
REF 30 Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013 Apr;28(4):899-911.
REF 31 Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial. Br J Cancer. 2002 Jun 17;86(12):1864-70.
REF 32 FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation. Int J Nanomedicine. 2012; 7: 5915-5927.
REF 33 Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
REF 34 Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)py... J Med Chem. 2008 Oct 9;51(19):5897-900.
REF 35 Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16.
REF 36 Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3595-9.
REF 37 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 38 Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor... J Med Chem. 2009 Jan 22;52(2):278-92.
REF 39 Company report (Fiveprime)
REF 40 Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol. 2000 Oct 1;60(7):885-98.
REF 41 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases. Bioorg Med Chem Lett. 2009 Feb 1;19(3):745-50.
REF 42 The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
REF 43 Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett. 2012 Jul 26;3(9):705-9.
REF 44 Design, synthesis and biological evaluation of novel FGFR inhibitors bearing an indazole scaffold. Org Biomol Chem. 2015 Jul 28;13(28):7643-54.
REF 45 Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3.

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