Ivosidenib
DRACPC ID DRACPC0023
Active Ingredients Ivosidenib
Description An orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1), with potential antineoplastic activity. Upon administration, AG-120 specifically inhibits a mutated form of IDH1 in the cytoplasm, which inhibits the formation of the oncometabolite, 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH1-expressing tumor cells. IDH1, an enzyme in the citric acid cycle, is mutated in a variety of cancers; it initiates and drives cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG.
Synonyms AG-120; Tibsovo; Ivosidenib
Type Small Molecule
Disease Acute Myeloid Leukemia, Cholangiocarcinoma
Classification
IDH1 inhibitor Amino acid and derivative
Structure Information
Molecular Formula C28H22ClF3N6O3
Molecular Weight 583
Active Sequence Not available
Sequence Length Not available
Modification Not available
IUPAC Name (2S)-N-[(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl]-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide
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
SMILES O=C([C@H](CC1)N(C2=NC=CC(C#N)=C2)C1=O)N([C@@H](C3=CC=CC=C3Cl)C(NC4CC(F)(F)C4)=O)C5=CC(F)=CN=C5
External Codes
PubChem CID 71657455
DrugBank Accession Number DB14568
NCI Thesaurus Code C114383
UNII Q2PCN8MAM6 GSRS
CAS 1448347-49-6
Drug approval
Drug indication
Ivosidenib is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:
1)Newly Diagnosed Acute Myeloid Leukemia (AML) in combination azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.
2)Relapsed or refractory AML in adults.
3)Locally Advanced or Metastatic Cholangiocarcinoma in adults who have been previously treated.
| Drug Name | Strength | Dosage Form/Route | Company | Marketing Status | Drug ID | Approval year |
|---|---|---|---|---|---|---|
| Tibsovo | 250mg | Tablet; Oral | Servier | Prescription | NDA: 211192 | 2018 |
| ClinicalTrials.gov Identifier | Title | Condition or disease | Phase | Purpose |
|---|---|---|---|---|
| NCT04176393 | A Phase 1, Multicenter, Single-Arm Study Evaluating Pharmacokinetic, Pharmacodynamic, Safety, and Clinical Efficacy of Orally Administered Ivosidenib in Chinese Subjects With Relapsed or Refractory Acute Myeloid Leukemia With an IDH1 Mutation | Relapsed or Refractory Acute Myeloid Leukemia | Phase 1 | Treatment |
| NCT03564821 | A Phase 1 Study of IDH1 Inhibition Using Ivosidenib as Maintenance Therapy for IDH1-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation | IDH1 Mutation Myeloid Neoplasms | Phase 1 | Treatment |
| NCT04056910 | Phase II Study of IDH1 Inhibitor Ivosidenib and Nivolumab in IDH1 Mutant Gliomas and Advanced Solid Tumors | Advanced Solid Tumor; IDH1 Mutation; Glioma | Phase 2 | Treatment |
| NCT02073994 | A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation | Cholangiocarcinoma; Chondrosarcoma; Glioma; Other Advanced Solid Tumors | Phase 1 | Treatment |
| NCT03245424 | Expanded Access Program for Ivosidenib (AG-120) Monotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia With an IDH1 Mutation | Acute Myeloid Leukemia; Relapsed Adult AML; Relapsed Pediatric AML | Treatment |
More clinical information is obtained from ClinicalTrials.gov.
