olutasidenib   Click here for help

GtoPdb Ligand ID: 10319

Synonyms: example 26 [US9834539B2] | FT-2102 | FT2102 | Rezlidhia®
Approved drug PDB Ligand
olutasidenib is an approved drug (FDA (2022))
Compound class: Synthetic organic
Comment: Olutasidenib (FT-2102) is an orally available and brain penetrant inhibitor of mutant IDH1 that is being developed by Forma Therapeutics for antineoplastic potential [1]. Activating mutations in IDH1 (e.g. IDH1R132H) drive cancer initiation and growth by enhancing the formation of the oncometabolite 2-hydroxyglutarate (2HG) [3]. Pharmacological inhibition of mutant IDH1 blocks 2HG production as a means to restore normal cellular differentiation. This is the same mechanism of action as ivosidenib (Tibsovo®) that was FDA approved in 2018.
FT-2102 is claimed as example 26 (I-14) in Forma Tm2's patent US9834539B2 [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 90.68
Molecular weight 354.09
XLogP 4.41
No. Lipinski's rules broken 0
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Canonical SMILES N#Cc1ccc(c(=O)n1C)NC(c1cc2cc(Cl)ccc2[nH]c1=O)C
Isomeric SMILES N#Cc1ccc(c(=O)n1C)N[C@H](c1cc2cc(Cl)ccc2[nH]c1=O)C
InChI InChI=1S/C18H15ClN4O2/c1-10(21-16-6-4-13(9-20)23(2)18(16)25)14-8-11-7-12(19)3-5-15(11)22-17(14)24/h3-8,10,21H,1-2H3,(H,22,24)/t10-/m0/s1
1. Caravella JA, Lin J, Diebold RB, Campbell AM, Ericsson A, Gustafson G, Wang Z, Castro J, Clarke A, Gotur D et al.. (2020)
Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor.
J Med Chem, 63 (4): 1612-1623. [PMID:31971798]
2. Lin J, Ericsson A, Campbell A-M, Gustafson G, Wang Z, Diebold RB, Ashwell S, Lancia DR Jr, Caravella A, Lu W. (2017)
Pyridin-2(1H)-one quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors.
Patent number: US9834539B2. Assignee: Forma Tm2 Inc. Priority date: 19/09/2014. Publication date: 05/12/2017.
3. Wang G, Sai K, Gong F, Yang Q, Chen F, Lin J. (2014)
Mutation of isocitrate dehydrogenase 1 induces glioma cell proliferation via nuclear factor-κB activation in a hypoxia-inducible factor 1-α dependent manner.
Mol Med Rep, 9 (5): 1799-805. [PMID:24626950]
4. Watts JM, Baer MR, Yang J, Prebet T, Lee S, Schiller GJ, Dinner SN, Pigneux A, Montesinos P, Wang ES et al.. (2022)
Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial.
Lancet Haematol, [Epub ahead of print]. DOI: 10.1016/S2352-3026(22)00292-7 [PMID:36370742]