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ivosidenib   Click here for help

GtoPdb Ligand ID: 9217

Synonyms: AG-120 | AG120 | Tibsovo®
Approved drug PDB Ligand
ivosidenib is an approved drug (FDA (2018), EMA (2023))
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.

ivosidenib is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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]