Ivosidenib

DCTPepD ID  DCTPepD0023

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

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

Structure

 

Show IUPAC/InChI/SMILES

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.





DCTPep is developed by Dr.Zheng's team.