Vorasidenib

Summary

Vorasidenib (CHEMBL4279047) is an approved small molecule (ATC L01XM04) targeting IDH1 and IDH2; indicated across 7 conditions including astrocytoma (excluding glioblastoma) and oligodendroglioma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01XM04
• Targets: 2 (IDH1, IDH2)
• Indications: 7 conditions
• Clinical trials: 18
• Chemistry: 414.74 Da · C14H13ClF6N6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4279047
Name	Vorasidenib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	117817422
ATC	L01XM04
Molecular formula	C14H13ClF6N6
Molecular weight	414.74
InChIKey	QCZAWDGAVJMPTA-RNFRBKRXSA-N

SMILES: C[C@H](C(F)(F)F)NC1=NC(=NC(=N1)C2=NC(=CC=C2)Cl)N[C@H](C)C(F)(F)F

IUPAC name: 6-(6-chloro-2-pyridinyl)-2-N,4-N-bis[(2R)-1,1,1-trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine

Also known as: Ag-881, AG-881, Voranigo, Vorasidenib, VORASIDENIB

Parent form; salt/anhydrous children: CHEMBL4594378

Patent coverage: 168 distinct patent families (504 SureChEMBL compound mentions), from 12 matched compound structure(s). One matched structure accounts for 364 (72%) 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
IDH2	isocitrate dehydrogenase (NADP(+)) 2	Inhibition		0.2%	P48735

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Isocitrate dehydrogenase [NADP] cytoplasmic, Isocitrate dehydrogenase [NADP], mitochondrial.

Bioactivity

ChEMBL activities: 14 potent at pChembl ≥ 5 of 15 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
IDH1	10.4	IC50	0.04	nM	CHEMBL_ACT_18863531
IDH1	10.4	IC50	0.04	nM	CHEMBL_ACT_18863532
IDH1	10.4	IC50	0.04	nM	CHEMBL_ACT_18863533
IDH1	10.4	IC50	0.04	nM	CHEMBL_ACT_18863534
IDH2	8.15	IC50	7	nM	CHEMBL_ACT_18863536
IDH1	7.68	IC50	21	nM	CHEMBL_ACT_25594749
IDH2	6.93	IC50	118	nM	CHEMBL_ACT_26147561
IDH2	6.89	IC50	130	nM	CHEMBL_ACT_18863535
IDH2	6.89	IC50	130	nM	CHEMBL_ACT_26147584
IDH1	6.72	IC50	190	nM	CHEMBL_ACT_26147566
IDH2	6.43	IC50	374	nM	CHEMBL_ACT_26147564
IDH1	6.4	IC50	395	nM	CHEMBL_ACT_25594736
IDH1	5.55	Kd	2800	nM	CHEMBL_ACT_25594831
IDH1	5.3	Kd	5000	nM	CHEMBL_ACT_25594838

Target pathways

Aggregated over 2 target gene(s): IDH1, IDH2.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Transcriptional activation of mitochondrial biogenesis	1	IDH2
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1	IDH1
NADPH regeneration	1	IDH1
Neutrophil degranulation	1	IDH1
Citric acid cycle (TCA cycle)	1	IDH2
Peroxisomal protein import	1	IDH1
NFE2L2 regulating TCA cycle genes	1	IDH1
Mitochondrial protein degradation	1	IDH2
Maturation of TCA enzymes and regulation of TCA cycle	1	IDH2

Dominant GO biological processes

GO term	Targets
glyoxylate cycle	2
tricarboxylic acid cycle	2
isocitrate metabolic process	2
2-oxoglutarate metabolic process	2
NADP+ metabolic process	2
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
carbohydrate metabolic process	1
NADP+ biosynthetic process	1
negative regulation of glial cell proliferation	1

Indications & clinical

Indications

7 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
astrocytoma (excluding glioblastoma)	4	MONDO:0019781	EFO:0000272
oligodendroglioma	4	MONDO:0016695	MONDO:0016695
paraganglioma	3	MONDO:0000448	EFO:1000453
neoplasm	1	MONDO:0005070	EFO:0000616
liver disorder	1	MONDO:0005154	EFO:0001421
glioma	1	MONDO:0021042	MONDO:0021637

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 18.

Phase distribution

Phase	Trials
PHASE1	8
PHASE3	4
Not specified	4
PHASE1/PHASE2	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04164901	PHASE3	ACTIVE_NOT_RECRUITING	Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
NCT06780930	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Study of Vorasidenib (S095032/AG-881) in Asian Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 orIDH2 Mutation
NCT06809322	PHASE3	RECRUITING	Vorasidenib Maintenance for IDH Mutant Astrocytoma
NCT07215910	PHASE3	NOT_YET_RECRUITING	Testing Addition of an Anti-cancer Drug, Vorasidenib to Temozolomide, After Radiation for Advanced Brain Cancer
NCT06478212	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Vorasidenib in Combination With Temozolomide (TMZ) in IDH-mutant Glioma
NCT07286292	PHASE2	NOT_YET_RECRUITING	Vorasidenib Study in Pediatric Participants With Grade 2 Astrocytoma or Oligodendroglioma With an IDH1 or IDH2 Mutation
NCT05484622	PHASE1	ACTIVE_NOT_RECRUITING	Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive IDH-1 Mutant Glioma
NCT05609994	PHASE1	RECRUITING	ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas
NCT07250633	PHASE1	NOT_YET_RECRUITING	Pharmacokinetic Study of Vorasidenib in Severe Hepatically Impaired and Matched-Control Participants
NCT03960502	PHASE1	COMPLETED	A Safety and Pharmacokinetic Study of AG-881 in Healthy Male Participants Following Administration of a Single Oral Dose of [14C] AG-881 and Concomitant Intravenous Microdose of [13C315N3] AG-881
NCT04015687	PHASE1	COMPLETED	A Study to Evaluate the Effect of AG-881 on the Pharmacokinetics of a Single Dose of Lamotrigine in Healthy Adults
NCT05674474	PHASE1	COMPLETED	A Study of Vorasidenib in Participants With Moderate or Mild Hepatic Impairment and Matched Participants With Normal Hepatic Function
NCT07235748	PHASE1	COMPLETED	Drug-drug Interaction Study of Vorasidenib With Bupropion, Repaglinide, Flurbiprofen, Omeprazole, Midazolam, and Rosuvastatin in Healthy Adult Participants
NCT07235774	PHASE1	COMPLETED	A Drug-drug Interaction Study of Vorasidenib and a Combined Oral Contraceptive in Healthy Female Participants
NCT06969352	Not specified	NOT_YET_RECRUITING	A Multicentre, Retrospective-prospective Real-world Study: to Evaluate the Effectiveness and Safety of Vorasidenib in Patients With Isocitrate Dehydrogenase IDH1/2 Mutant Grade 2 Astrocytoma or Oligodendroglioma (VICTORIA Study)
NCT07240662	Not specified	RECRUITING	Vorasidenib in CNS WHO Grade 2 IDH-mutant Diffuse Glioma
NCT07547163	Not specified	RECRUITING	Patient Voice in the Treatment of Low-grade Gliomas: Use of Patient-reported Outcomes, Vorasidenib and Radiotherapy Compared
NCT05592743	Not specified	APPROVED_FOR_MARKETING	Vorasidenib Expanded Access Program

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

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.

9 molecules share ≥1 primary target. Top 9 by shared-target count:

Molecule	Source	Status	Shared targets
ENASIDENIB	ChEMBL + PubChem	Phase 4 (approved)	IDH1, IDH2
IVOSIDENIB	ChEMBL + PubChem	Phase 4 (approved)	IDH1, IDH2
OLUTASIDENIB	ChEMBL + PubChem	Phase 4 (approved)	IDH1, IDH2
CRELOSIDENIB	ChEMBL	Phase 2	IDH1, IDH2
DS-1001B	ChEMBL	Phase 2	IDH1
IDH305	ChEMBL	Phase 2	IDH1
RANOSIDENIB	ChEMBL	Phase 2	IDH2
SAFUSIDENIB	ChEMBL	Phase 2	IDH1
ZUCLOMIPHENE	ChEMBL	Phase 2	IDH1