futibatinib   Click here for help

GtoPdb Ligand ID: 9786

Synonyms: Example 2 [WO2013108809] | FGFR-IN-1 | Lytgobi® | TAS 120 | TAS-120 | TAS120
Approved drug PDB Ligand
futibatinib is an approved drug (FDA (2022), EMA (2023))
Compound class: Synthetic organic
Comment: Futibatinib (TAS-120) is a covalent (irreversible), non-selective FGFR inhibitor that was developed for anti-tumour activity [5]. It is claimed as Example 2 in patent WO2013108809 [4]. It can overcome acquired resistance to ATP-competitive FGFR inhibitors (such as infigratinib and zoligratinib) in intrahepatic cholangiocarcinomas that harbour FGFR2 kinase domain mutations [2]. A case study in a patient with metastatic cholangiocarcinoma, whose tumour had a FGFR2-CORO2B gene fusion and a pemigatinib-induced resistance mutation, demonstrated tumour shrinkage in response to futibatinib treatment [3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 108.39
Molecular weight 418.18
XLogP 2.77
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)N1CCC(C1)n1nc(c2c1ncnc2N)C#Cc1cc(OC)cc(c1)OC
Isomeric SMILES C=CC(=O)N1CC[C@@H](C1)n1nc(c2c1ncnc2N)C#Cc1cc(OC)cc(c1)OC
InChI InChI=1S/C22H22N6O3/c1-4-19(29)27-8-7-15(12-27)28-22-20(21(23)24-13-25-22)18(26-28)6-5-14-9-16(30-2)11-17(10-14)31-3/h4,9-11,13,15H,1,7-8,12H2,2-3H3,(H2,23,24,25)/t15-/m0/s1
InChI Key KEIPNCCJPRMIAX-HNNXBMFYSA-N
References
1. Bahleda R, Meric-Bernstam F, Goyal L, Tran B, He Y, Yamamiya I, Benhadji KA, Matos I, Arkenau HT. (2020)
Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors.
Ann Oncol, 31 (10): 1405-1412. [PMID:32622884]
2. Goyal L, Shi L, Liu LY, Fece de la Cruz F, Lennerz JK, Raghavan S, Leschiner I, Elagina L, Siravegna G, Ng RWS et al.. (2019)
TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma.
Cancer Discov, 9 (8): 1064-1079. [PMID:31109923]
3. Rengan AK, Denlinger CS. (2022)
Robust Response to Futibatinib in a Patient With Metastatic FGFR-Addicted Cholangiocarcinoma Previously Treated Using Pemigatinib.
J Natl Compr Canc Netw, 20 (5): 430-435. [PMID:35378504]
4. Sagara T, Ito S, Otsuki S, Sootome H. (2013)
3,5-disubstituted alkynylbenzene compound and salt thereof.
Patent number: WO2013108809. Assignee: Taiho Pharmaceutical Co., Ltd.. Priority date: 19/01/2012. Publication date: 25/07/2013.
5. Sootome H, Fujita H, Ito K, Ochiiwa H, Fujioka Y, Ito K, Miura A, Sagara T, Ito S, Ohsawa H et al.. (2020)
Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors.
Cancer Res, 80 (22): 4986-4997. [PMID:32973082]