Target Information
| Target General Information | Top | |||||
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| Target ID |
T47101
(Former ID: TTDC00024)
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| Target Name |
Fibroblast growth factor receptor 1 (FGFR1)
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| 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
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| Gene Name |
FGFR1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Colorectal cancer [ICD-11: 2B91] | |||||
| 2 | Idiopathic interstitial pneumonitis [ICD-11: CB03] | |||||
| 3 | Liver cancer [ICD-11: 2C12] | |||||
| 4 | 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.
Click to Show/Hide
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.10.1
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| Sequence |
MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDD
VQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSD ALPSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPS SGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSIN HTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKI GPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLE ALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKS IPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRDRLVL GKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGK HKNIINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGLEYCYNPSHNPEEQLSSKDL VSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNG RLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMD KPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSF PDTRSSTCSSGEDSVFSHEPLPEEPCLPRHPAQLANGGLKRR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T55JB4 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Intedanib | Drug Info | Approved | Colorectal cancer | [2] | |
| 2 | Pemigatinib | Drug Info | Approved | Cholangiocarcinoma | [3] | |
| 3 | Romiplostim | Drug Info | Approved | Thrombocytopenia | [4], [5] | |
| Clinical Trial Drug(s) | [+] 13 Clinical Trial Drugs | + | ||||
| 1 | ARQ-087 | Drug Info | Phase 3 | Intrahepatic cholangiocarcinoma | [6] | |
| 2 | BGJ398 | Drug Info | Phase 3 | Cholangiocarcinoma | [7] | |
| 3 | E-3810 | Drug Info | Phase 3 | Solid tumour/cancer | [8], [9] | |
| 4 | Rosiglitazone + metformin | Drug Info | Phase 3 | Diabetic complication | [10] | |
| 5 | Sulfatinib | Drug Info | Phase 3 | Neuroendocrine cancer | [11] | |
| 6 | AZD4547 | Drug Info | Phase 2/3 | Solid tumour/cancer | [12], [13] | |
| 7 | AM-001 | Drug Info | Phase 2 | Dermatological disease | [14] | |
| 8 | Debio 1347 | Drug Info | Phase 2 | Solid tumour/cancer | [15] | |
| 9 | FGF-1 | Drug Info | Phase 2 | Coronary heart disease | [16] | |
| 10 | FP-1039 | Drug Info | Phase 2 | Endometrial cancer | [17] | |
| 11 | MK-2461 | Drug Info | Phase 1/2 | Alzheimer disease | [18] | |
| 12 | KW-2449 | Drug Info | Phase 1 | Acute myeloid leukaemia | [19], [20] | |
| 13 | NGM313 | Drug Info | Phase 1 | Type-2 diabetes | [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 | [+] 4 Modulator drugs | + | ||||
| 1 | Intedanib | Drug Info | [2] | |||
| 2 | BGJ398 | Drug Info | [25] | |||
| 3 | AZD4547 | Drug Info | [30] | |||
| 4 | NGM313 | Drug Info | [21] | |||
| Inhibitor | [+] 27 Inhibitor drugs | + | ||||
| 1 | Pemigatinib | Drug Info | [3] | |||
| 2 | Romiplostim | Drug Info | [1] | |||
| 3 | ARQ-087 | Drug Info | [24] | |||
| 4 | E-3810 | Drug Info | [26] | |||
| 5 | Rosiglitazone + metformin | Drug Info | [27], [28] | |||
| 6 | Sulfatinib | Drug Info | [29] | |||
| 7 | Debio 1347 | Drug Info | [6] | |||
| 8 | MK-2461 | Drug Info | [18] | |||
| 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 | [24] | |||
| 16 | HKI-9924129 | Drug Info | [39] | |||
| 17 | NP-506 | Drug Info | [40] | |||
| 18 | PD-0166326 | Drug Info | [39] | |||
| 19 | PD-0173952 | Drug Info | [39] | |||
| 20 | PD-0173955 | Drug Info | [39] | |||
| 21 | PD-0173956 | Drug Info | [39] | |||
| 22 | PD-0173958 | Drug Info | [39] | |||
| 23 | PD-0179483 | Drug Info | [39] | |||
| 24 | PMID22765894C8h | Drug Info | [41] | |||
| 25 | PMID24900538C2c | Drug Info | [42] | |||
| 26 | PMID26080733C7r | Drug Info | [43] | |||
| 27 | Ro-4396686 | Drug Info | [44] | |||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | AM-001 | Drug Info | [31] | |||
| 2 | FP-1039 | Drug Info | [33] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | FGF-1 | Drug Info | [32] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | SAR-106881 | Drug Info | [24] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| 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 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020 | |||||
| REF 4 | 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 5 | 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6. | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | ClinicalTrials.gov (NCT03773302) Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations. U.S. National Institutes of Health. | |||||
| REF 8 | 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 9 | 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 10 | 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 11 | ClinicalTrials.gov (NCT02589821) Phase III Study of Surufatinib in Treating Advanced Pancreatic Neuroendocrine Tumors. 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: 7707). | |||||
| REF 13 | 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 14 | ClinicalTrials.gov (NCT01938599) Study Comparing AM001 Cream to Vehicle in the Treatment of Plaque Psoriasis. U.S. National Institutes of Health. | |||||
| REF 15 | ClinicalTrials.gov (NCT03834220) Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial). U.S. National Institutes of Health. | |||||
| REF 16 | 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 17 | ClinicalTrials.gov (NCT01244438) Study of FP-1039 in Subjects With Endometrial Cancers. U.S. National Institutes of Health. | |||||
| REF 18 | MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33. | |||||
| REF 19 | 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 20 | 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 21 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| 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 | 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 25 | 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 26 | 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 27 | 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 28 | 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 29 | Clinical pipeline report, company report or official report of Hutchison Medi Pharma. | |||||
| REF 30 | 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 31 | 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 32 | Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial. Br J Cancer. 2002 Jun 17;86(12):1864-70. | |||||
| REF 33 | FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation. Int J Nanomedicine. 2012; 7: 5915-5927. | |||||
| 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 | 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 40 | 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 41 | The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85. | |||||
| REF 42 | 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 43 | Design, synthesis and biological evaluation of novel FGFR inhibitors bearing an indazole scaffold. Org Biomol Chem. 2015 Jul 28;13(28):7643-54. | |||||
| REF 44 | 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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