ivosidenib   Click here for help

GtoPdb Ligand ID: 9217

Synonyms: AG-120 | AG120 | Tibsovo®
Approved drug
ivosidenib is an approved drug (FDA (2018))
Compound class: Synthetic organic
Comment: Ivosidenib (AG-120) is an orally active, selective inhibitor of isocitrate dehydrogenase 1 (IDH1) [5], in particular with activity against IDH1 R132H or R132C mutants. It is one of the compounds claimed in Agios' patent WO2013107291, where it is Compound 176 [4]. It is structurally related to AGI-5198 also from Agios.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 119.29
Molecular weight 582.14
XLogP 3.28
No. Lipinski's rules broken 0
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Canonical SMILES N#Cc1ccnc(c1)N1C(=O)CCC1C(=O)N(C(c1ccccc1Cl)C(=O)NC1CC(C1)(F)F)c1cncc(c1)F
Isomeric SMILES N#Cc1ccnc(c1)N1C(=O)CC[C@H]1C(=O)N([C@@H](c1ccccc1Cl)C(=O)NC1CC(C1)(F)F)c1cncc(c1)F
InChI InChI=1S/C28H22ClF3N6O3/c29-21-4-2-1-3-20(21)25(26(40)36-18-11-28(31,32)12-18)37(19-10-17(30)14-34-15-19)27(41)22-5-6-24(39)38(22)23-9-16(13-33)7-8-35-23/h1-4,7-10,14-15,18,22,25H,5-6,11-12H2,(H,36,40)/t22-,25-/m0/s1
1. Birendra KC, DiNardo CD. (2016)
Evidence for Clinical Differentiation and Differentiation Syndrome in Patients With Acute Myeloid Leukemia and IDH1 Mutations Treated With the Targeted Mutant IDH1 Inhibitor, AG-120.
Clin Lymphoma Myeloma Leuk, 16 (8): 460-5. [PMID:27245312]
2. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC et al.. (2009)
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.
Nature, 462 (7274): 739-44. [PMID:19935646]
3. DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA et al.. (2018)
Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML.
N Engl J Med, 378 (25): 2386-2398. [PMID:29860938]
4. Lemieux RM, Popovici-Muller J, Travins J, Cai Z, Cui D, Zhou D. (2013)
Therapeutically active compounds and their methods of use.
Patent number: WO2013107291. Assignee: Agios Pharmaceuticals, Inc.. Priority date: 19/01/2012. Publication date: 25/07/2013.
5. Popovici-Muller J, Lemieux RM, Artin E, Saunders JO, Salituro FG, Travins J, Cianchetta G, Cai Z, Zhou D, Cui D et al.. (2018)
Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers.
ACS Med Chem Lett, 9 (4): 300-305. [PMID:29670690]