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
SMILES / InChI / InChIKey
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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
InChI Key WIJZXSAJMHAVGX-DHLKQENFSA-N
References
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]