Ivosidenib

Summary

Ivosidenib (CHEMBL3989958) is an approved small-molecule antineoplastic agent (ATC L01XM02) targeting IDH1; indicated across 11 conditions including acute myeloid leukemia and cholangiocarcinoma; with CIViC clinical evidence for 10 variant-indication associations (e.g. IDH1 R132 AND IDH1 R132L in acute myeloid leukemia).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01XM02
• Targets: 1 (IDH1)
• Indications: 11 conditions
• Clinical trials: 55
• Precision-oncology evidence (CIViC): 10 variant–indication associations
• Chemistry: 583 Da · C28H22ClF3N6O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3989958
Name	Ivosidenib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	71657455
ChEBI	CHEBI:145430
ATC	L01XM02
Molecular formula	C28H22ClF3N6O3
Molecular weight	583
InChIKey	WIJZXSAJMHAVGX-DHLKQENFSA-N

SMILES: C1CC(=O)N([C@@H]1C(=O)N(C2=CC(=CN=C2)F)[C@@H](C3=CC=CC=C3Cl)C(=O)NC4CC(C4)(F)F)C5=NC=CC(=C5)C#N

IUPAC name: (2S)-N-[(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl]-1-(4-cyano-2-pyridinyl)-N-(5-fluoro-3-pyridinyl)-5-oxopyrrolidine-2-carboxamide

ChEBI definition: A tertiary carboxamide resulting from the formal condensation of the carboxy group of (2S)-1-(4-cyanopyridin-2-yl)-5-oxopyrrolidine-2-carboxylic acid with the secondary amino group of (2S)-2-(2-chlorophenyl)-N-(3,3-difluorocyclobutyl)-2-[(5-fluoropyridin-3-yl)amino]acetamide. It is approved by the FDA for the treatment of acute myeloid leukemia (AML) in patients with an isocitrate dehydrogenase-1 (IDH1) mutation.

Pharmacological roles (ChEBI): antineoplastic agent, EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor.

Also known as: AG-120, Ivosidenib, Tibsovo, IVOSIDENIB, ivosidenib

Patent coverage: 936 distinct patent families (2,231 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 2,201 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
IDH1	isocitrate dehydrogenase (NADP(+)) 1	Inhibition		0.7%	O75874

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Isocitrate dehydrogenase [NADP] cytoplasmic, Isocitrate dehydrogenase [NADP], mitochondrial, Bile salt export pump.

Bioactivity

ChEMBL activities: 33 potent at pChembl ≥ 5 of 35 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
IDH1	8.46	IC50	3.5	nM	CHEMBL_ACT_19282120
IDH1	8.35	IC50	4.5	nM	CHEMBL_ACT_25654644
IDH1	8.31	IC50	4.9	nM	CHEMBL_ACT_25594737
IDH1	8.12	IC50	7.5	nM	CHEMBL_ACT_18461489
IDH1	7.92	IC50	12	nM	CHEMBL_ACT_26147603
IDH1	7.92	IC50	12	nM	CHEMBL_ACT_26147612
IDH1	7.92	IC50	12	nM	CHEMBL_ACT_28678448
IDH1	7.92	IC50	12	nM	CHEMBL_ACT_28735268
IDH1	7.92	IC50	12	nM	CHEMBL_ACT_28943051
IDH1	7.9	EC50	12.47	nM	CHEMBL_ACT_23161012
IDH1	7.89	IC50	13	nM	CHEMBL_ACT_26147604
IDH1	7.89	IC50	13	nM	CHEMBL_ACT_28943054
IDH1	7.72	IC50	19	nM	CHEMBL_ACT_18461488
IDH1	7.72	IC50	19	nM	CHEMBL_ACT_25654711
IDH1	7.64	IC50	23	nM	CHEMBL_ACT_19282146
IDH1	7.59	IC50	25.4	nM	CHEMBL_ACT_19282094
IDH1	7.57	EC50	27.23	nM	CHEMBL_ACT_23161015
IDH1	7.56	IC50	27.73	nM	CHEMBL_ACT_25859858
IDH1	7.47	IC50	33.86	nM	CHEMBL_ACT_25859890
IDH1	7.3	IC50	50	nM	CHEMBL_ACT_25654684
IDH1	7.2	IC50	63	nM	CHEMBL_ACT_23160858
IDH1	7.19	IC50	65	nM	CHEMBL_ACT_23160695
IDH1	7.15	IC50	71	nM	CHEMBL_ACT_26147568
IDH1	6.38	Kd	420	nM	CHEMBL_ACT_25594809
IDH1	6.31	Kd	490	nM	CHEMBL_ACT_25594817
IDH1	5.7	IC50	2000	nM	CHEMBL_ACT_25594724
IDH1	5.43	IC50	3690	nM	CHEMBL_ACT_28678451
IDH1	5.43	IC50	3690	nM	CHEMBL_ACT_28735271
IDH2	5.14	IC50	7200	nM	CHEMBL_ACT_26147562
IDH1	5.05	Kd	9000	nM	CHEMBL_ACT_25594832
IDH1	5.01	Kd	9700	nM	CHEMBL_ACT_25594839
IDH1	5.01	IC50	9741	nM	CHEMBL_ACT_25859922
IDH1	5	Kd	10000	nM	CHEMBL_ACT_25594825

Target pathways

Aggregated over 1 target gene(s): IDH1.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1	IDH1
NADPH regeneration	1	IDH1
Neutrophil degranulation	1	IDH1
Peroxisomal protein import	1	IDH1
NFE2L2 regulating TCA cycle genes	1	IDH1

Dominant GO biological processes

GO term	Targets
glyoxylate cycle	1
tricarboxylic acid cycle	1
isocitrate metabolic process	1
2-oxoglutarate metabolic process	1
NADP+ metabolic process	1
NADPH regeneration	1
glutathione metabolic process	1
response to oxidative stress	1
female gonad development	1
response to steroid hormone	1
regulation of phospholipid catabolic process	1
regulation of phospholipid biosynthetic process	1

Indications & clinical

Indications

4 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
acute myeloid leukemia	4	MONDO:0018874	EFO:0000222
cholangiocarcinoma	4	MONDO:0019087	EFO:0005221
myelodysplastic syndrome	3	MONDO:0018881	EFO:0000198
biliary tract neoplasm	3	MONDO:0005304	EFO:0003891

7 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
chondrosarcoma	2	MONDO:0008977	EFO:0000333
neoplasm	2	MONDO:0005070	MONDO:0004992
paraganglioma	2	MONDO:0000448	EFO:1000453
liver disorder	1	MONDO:0005154	EFO:0001421
leukemia	1	MONDO:0005059	EFO:0000565
myeloid leukemia	1	MONDO:0004643	MONDO:0004643
pancreatic ductal adenocarcinoma	1	MONDO:0005184	MONDO:0005184

Clinical trials

Total trials: 55.

Phase distribution

Phase	Trials
PHASE2	20
PHASE1	17
PHASE3	7
PHASE1/PHASE2	7
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03173248	PHASE3	ACTIVE_NOT_RECRUITING	Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
NCT03839771	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Ivosidenib or Enasidenib in Combination With Induction Therapy and Consolidation Therapy, Followed by Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myedysplastic Syndrome EB2, With an IDH1 or IDH2 Mutation, Respectively, Eligible for Intensive Chemotherapy
NCT05615818	PHASE3	RECRUITING	Personalized Medicine for Advanced Biliary Cancer Patients
NCT05876754	PHASE3	RECRUITING	An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma
NCT06127407	PHASE3	RECRUITING	Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen
NCT06465953	PHASE3	RECRUITING	Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation
NCT02989857	PHASE3	COMPLETED	Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)
NCT02677922	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy
NCT03013998	PHASE1/PHASE2	RECRUITING	Study of Biomarker-Based Treatment of Acute Myeloid Leukemia
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03471260	PHASE1/PHASE2	RECRUITING	Ivosidenib and Venetoclax With or Without Azacitidine in Treating Patients With IDH1 Mutated Hematologic Malignancies
NCT03503409	PHASE2	ACTIVE_NOT_RECRUITING	IDH1 (AG 120) Inhibitor in Patients With IDH1 Mutated Myelodysplastic Syndrome
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04278781	PHASE2	ACTIVE_NOT_RECRUITING	AG-120 in People With IDH1 Mutant Chondrosarcoma
NCT04493164	PHASE2	RECRUITING	CPX-351 and Ivosidenib for the Treatment of IDH1 Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
NCT04774393	PHASE1/PHASE2	RECRUITING	Decitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
NCT05030441	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH1
NCT05401097	PHASE2	RECRUITING	IDH Targeted/Non- Targeted vs Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)
NCT06081829	PHASE2	ACTIVE_NOT_RECRUITING	A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
NCT06501625	PHASE1/PHASE2	RECRUITING	Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation
NCT06593548	PHASE2	NOT_YET_RECRUITING	Lvosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer
NCT06611839	PHASE1/PHASE2	RECRUITING	Venetoclax in Combination With Ivosidenib and Azacitidine for Newly Diagnosed IDH1-Mutated AML
NCT06707493	PHASE2	RECRUITING	Ivosidenib as Post-HSCT Maintenance for AML
NCT07260175	PHASE2	RECRUITING	Phase II Study Evaluating Ivosidenib Maintenance After SOC Adjuvant Chemotherapy in Curative mIDH1 Cholangiocarcinoma
NCT07282262	PHASE2	RECRUITING	An Exploratory Study on the Use of Ivosidenib for the Precise Treatment of Advanced Biliary Tract Malignancies With IDH1 Mutations in the Later Line of Therapy.
NCT07392242	PHASE2	RECRUITING	A Study of the Combination of Ivosidenib, Azacitidine, and Venetoclax Followed by Ivosidenib Alone in People With Acute Myeloid Leukemia
NCT07463768	PHASE2	NOT_YET_RECRUITING	Study Evaluating the Efficacy and Safety of the Addition of Ivosidenib to Oral Azacitidine (Onureg®) in Patients Over 55 With Acute Myeloid Leukemia (AML) and IDH1 Mutation, in Complete Remission After Intensive Chemotherapy.
NCT07507760	PHASE2	NOT_YET_RECRUITING	Oral Decitabine Plus Ivosidenib as First Line for Older/Unfit Adult AML Patients
NCT07548710	PHASE2	RECRUITING	Study of SA+X in the Treatment of Newly Diagnosed AML
NCT07607418	PHASE2	RECRUITING	Ivosidenib as Maintenance Therapy in Transplant-Ineligible IDH1-mutated AML and HR-MDS
NCT03498521	PHASE2	COMPLETED	A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site
NCT04044209	PHASE2	WITHDRAWN	A Study of the IDH1 Inhibitor AG-120 in Combination With the Checkpoint Blockade Inhibitor, Nivolumab, for Patients With IDH1 Mutated Relapsed/Refractory AML and High Risk MDS
NCT04056910	PHASE2	COMPLETED	Ivosidenib (AG-120) With Nivolumab in IDH1 Mutant Tumors
NCT05921760	PHASE1/PHASE2	TERMINATED	Ivosidenib, Nivolumab, and Ipilimumab Combination in Previously Treated Subjects With Nonresectable or Metastatic IDH1 Mutant Cholangiocarcinoma
NCT02074839	PHASE1	RECRUITING	Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation
NCT02632708	PHASE1	ACTIVE_NOT_RECRUITING	Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation
NCT05010772	PHASE1	RECRUITING	Decitabine Alone or in Combination With Venetoclax, Gilteritinib, Enasidenib, or Ivosidenib as Maintenance Therapy for the Treatment of Acute Myeloid Leukemia in Remission
NCT05209074	PHASE1	ACTIVE_NOT_RECRUITING	Ivosidenib + mFOLFIRINOX in Patients With Resectable Pancreatic Adenocarcinoma
NCT05756777	PHASE1	RECRUITING	A Study of Gilteritinib in Combination With Ivosidenib or Enasidenib in People With Acute Myeloid Leukemia (AML)
NCT06291987	PHASE1	RECRUITING	Ivosidenib and Ruxolitinib in Patients With Advanced Myeloproliferative Neoplasms (MPNs) That Have an IDH1 Gene Mutation
NCT07006688	PHASE1	RECRUITING	A Study of an IDH1m Inhibitor in Participants With IDH1-Mutated Malignancies and Hepatic or Renal Impairment
NCT02073994	PHASE1	COMPLETED	Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation
NCT03071770	PHASE1	COMPLETED	Japanese Bridging Study of Ivosidenib (AG-120) in Healthy Subjects
NCT03282513	PHASE1	COMPLETED	A Study of AG-120 (Ivosidenib) in Subjects With Mild or Moderate Hepatic Impairment or Normal Hepatic Function
NCT03343197	PHASE1	COMPLETED	Study of AG-120 and AG-881 in Subjects With Low Grade Glioma
NCT03564821	PHASE1	COMPLETED	IDH1 Inhibition Using Ivosidenib as Maintenance Therapy for IDH1-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation
NCT04088188	PHASE1	TERMINATED	Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma
NCT04176393	PHASE1	COMPLETED	A China Bridging Study of Ivosidenib in r/r AML Subjects With an IDH1 Mutation
NCT04250051	PHASE1	TERMINATED	Ivosidenib and Combination Chemotherapy for the Treatment of IDH1 Mutant Relapsed or Refractory Acute Myeloid Leukemia
NCT04655391	PHASE1	WITHDRAWN	Glasdegib-Based Treatment Combinations for the Treatment of Patients With Relapsed Acute Myeloid Leukemia Who Have Undergone Hematopoietic Cell Transplantation
NCT04955938	PHASE1	WITHDRAWN	A Study of Fedratinib With IDH Inhibition in Advanced-Phase, IDH-Mutated Ph-Negative Myeloproliferative Neoplasms
NCT06265545	Not specified	RECRUITING	Multicenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia
NCT07131059	Not specified	RECRUITING	MRD-positive AML Clinical Study
NCT03245424	Not specified	APPROVED_FOR_MARKETING	Ivosidenib Expanded Access Program in Relapsed/Refractory AML With an IDH1 Mutation
NCT06181734	Not specified	COMPLETED	Ivosidenib (TIBSOVO®) Combined With Azacitidine According to Current SmPC

Clinical evidence (CIViC)

Variant × indication × effect (10 predictive associations from 11 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
IDH1 R132 AND IDH1 R132L	Acute Myeloid Leukemia	Sensitivity/Response	Ivosidenib	CIViC A	EID12899 +1
IDH1 Mutation	Acute Myeloid Leukemia	Sensitivity/Response	Ivosidenib + Azacitidine	CIViC A	EID10313
IDH1 Mutation	Acute Myeloid Leukemia	Sensitivity/Response	Ivosidenib	CIViC A	EID7278
IDH1 R132	Cholangiocarcinoma	Sensitivity/Response	Ivosidenib	CIViC A	EID10886
IDH1 R132	Chondrosarcoma	Sensitivity/Response	Ivosidenib	CIViC A	EID11194
IDH1 Mutation	Cholangiocarcinoma	Sensitivity/Response	Ivosidenib	CIViC B	EID7447
IDH1 R132C	Acute Myeloid Leukemia	Sensitivity/Response	Ivosidenib	CIViC B	EID2331
IDH1 R132S	Acute Myeloid Leukemia	Sensitivity/Response	Ivosidenib	CIViC B	EID2340
IDH1 R132H	Pancreatic Ductal Adenocarcinoma	Sensitivity/Response	Ivosidenib	CIViC C	EID5987
IDH1 R132 AND IDH1 R132C AND IDH1 R132H AND IDH1 R132L	Acute Myeloid Leukemia	Sensitivity/Response	Ivosidenib	CIViC D	EID12903

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

8 molecules share ≥1 primary target. Top 8 by shared-target count:

Molecule	Source	Status	Shared targets
OLUTASIDENIB	ChEMBL + PubChem	Phase 4 (approved)	IDH1
VORASIDENIB	ChEMBL + PubChem	Phase 4 (approved)	IDH1
ENASIDENIB	ChEMBL	Phase 4 (approved)	IDH1
CRELOSIDENIB	ChEMBL	Phase 2	IDH1
DS-1001B	ChEMBL	Phase 2	IDH1
IDH305	ChEMBL	Phase 2	IDH1
SAFUSIDENIB	ChEMBL	Phase 2	IDH1
ZUCLOMIPHENE	ChEMBL	Phase 2	IDH1