IDH2

Summary

IDH2 (isocitrate dehydrogenase (NADP(+)) 2, HGNC:5383) is a protein-coding gene on chromosome 15q26.1, encoding Isocitrate dehydrogenase [NADP], mitochondrial (P48735). Plays a role in intermediary metabolism and energy production. In precision oncology, IDH2 Mutation confers sensitivity to Enasidenib in Acute Myeloid Leukemia (CIViC Level A); 4 further curated variant–drug associations are listed below.

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the mitochondria. It plays a role in intermediary metabolism and energy production. This protein may tightly associate or interact with the pyruvate dehydrogenase complex. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3418 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 294 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 55
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 5 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• MANE Select transcript: NM_002168

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5383
Approved symbol	IDH2
Name	isocitrate dehydrogenase (NADP(+)) 2
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	IDH-2
Ensembl gene	ENSG00000182054
Ensembl biotype	protein_coding
OMIM	147650
Entrez	3418

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 nonsense_mediated_decay

ENST00000330062, ENST00000540499, ENST00000559482, ENST00000560061, ENST00000864221, ENST00000864222, ENST00000864223, ENST00000864224, ENST00000864225, ENST00000864226, ENST00000864227, ENST00000864228, ENST00000864229, ENST00000948834, ENST00000948835

RefSeq mRNA: 3 — MANE Select: NM_002168 NM_001289910, NM_001290114, NM_002168

CCDS: CCDS10359, CCDS76792

Canonical transcript exons

ENST00000330062 — 11 exons

Exon	Start	End
ENSE00001320250	90090479	90090644
ENSE00001329680	90083045	90084353
ENSE00003501198	90087439	90087575
ENSE00003572737	90085275	90085387
ENSE00003620744	90088587	90088747
ENSE00003623798	90084816	90084908
ENSE00003635454	90088359	90088502
ENSE00003679377	90085001	90085098
ENSE00003682238	90091553	90091644
ENSE00003689931	90087112	90087263
ENSE00003903163	90102276	90102468

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 70.1829 / max 916.7405, expressed in 1815 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151561	67.6779	1815
151559	1.3830	601
151558	0.5734	275
151560	0.5486	263

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.52	gold quality
gastrocnemius	UBERON:0001388	99.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.43	gold quality
body of tongue	UBERON:0011876	99.37	gold quality
vastus lateralis	UBERON:0001379	99.31	gold quality
triceps brachii	UBERON:0001509	99.26	gold quality
cardiac ventricle	UBERON:0002082	99.24	gold quality
heart left ventricle	UBERON:0002084	99.24	gold quality
skeletal muscle tissue	UBERON:0001134	99.23	gold quality
gluteal muscle	UBERON:0002000	99.21	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.13	gold quality
heart right ventricle	UBERON:0002080	99.12	gold quality
quadriceps femoris	UBERON:0001377	99.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.01	gold quality
biceps brachii	UBERON:0001507	98.95	gold quality
muscle organ	UBERON:0001630	98.89	gold quality
diaphragm	UBERON:0001103	98.85	gold quality
muscle of leg	UBERON:0001383	98.79	gold quality
deltoid	UBERON:0001476	98.78	gold quality
left ventricle myocardium	UBERON:0006566	98.74	gold quality
renal medulla	UBERON:0000362	98.58	gold quality
tibialis anterior	UBERON:0001385	98.47	gold quality
right lobe of liver	UBERON:0001114	98.44	gold quality
adult mammalian kidney	UBERON:0000082	98.37	gold quality
muscle tissue	UBERON:0002385	98.30	gold quality
body of stomach	UBERON:0001161	98.23	gold quality
right atrium auricular region	UBERON:0006631	98.23	gold quality
body of pancreas	UBERON:0001150	98.21	gold quality
metanephros cortex	UBERON:0010533	98.17	gold quality
tongue	UBERON:0001723	98.11	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	569.30
E-MTAB-11121	yes	503.86
E-GEOD-125970	yes	496.91
E-MTAB-9221	yes	418.13
E-HCAD-4	yes	139.97
E-MTAB-6701	yes	114.57
E-MTAB-9467	yes	49.11
E-CURD-122	yes	26.31
E-HCAD-5	yes	18.95
E-HCAD-10	yes	14.34
E-CURD-114	yes	11.68
E-MTAB-9388	yes	11.25
E-MTAB-10553	yes	7.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting IDH2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-6729-3P	96.91	66.79	703
HSA-MIR-6869-3P	83.17	65.88	30

Literature-anchored findings (GeneRIF, showing 40)

• IDPm may play an important role in regulating apoptosis induced by TNF-alpha and anticancer drugs and the sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer chemotherapy. (PMID:17854715)
• These results indicate that IDPm may play an important role in regulating the apoptosis induced by heat shock. (PMID:18096511)
• HOCl-mediated damage to IDPm may result in the perturbation of the cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition (PMID:18484410)
• Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas. (PMID:19228619)
• Mutations of IDH2 is not detected in brain metastases of colorectal cancer. (PMID:19350208)
• IDH2 codon 172 mutation is not associated with cancers. (PMID:19530255)
• In patients with glioma, IDH2 mutations predominantly occur in oligodendroglial tumors. (PMID:19554337)
• Studies indicate that mutations in IDH1/IDH2 are specific for diffuse gliomas. (PMID:19667985)
• IDH1 or IDH2 mutation plays a role in early tumor progression of several types of glioma (PMID:19765000)
• IDH1 and 2 mutations are very rare in paragangliomas and pheochromocytomas and do not appear to play an important role in oncogenic HIF activation known to be present in these tumors. (PMID:19915015)
• testing for IDH1/2 mutations can be effectively performed in a clinical setting and can enhance the accuracy of diagnosis of gliomas (PMID:19915484)
• IDH2 mutation confer an enzymatic gain of function that dramatically increases 2-hydroxyglutarate in acute myelogenous leukemia (PMID:20142433)
• In 46% of cases with anaplastic oligodendroglioma an IDH1 mutation was found and only one IDH2 mutation was identified. (PMID:20160062)
• Some patients with cytogenetically normal acute myeloid leukemia and elevated 2-hydroxyglutarate possessed IDH2 mutations. (PMID:20171147)
• Mutations in IDH seem to play an important role in the formation of specific subtypes of gliomas. (PMID:20367200)
• IDH1 and IDH2 mutations are recurrent in de novo cytogenetically normal acute myeloid leukemia and have an unfavorable impact on outcome. (PMID:20368543)
• Mutations of IDH2 genes is associated with early and accelerated phases of myelodysplastic syndromes and myeloproliferative neoplasms. (PMID:20376084)
• IDH2 gene mutation is associated with blast-phase myeloproliferative neoplasms. (PMID:20410924)
• IDH2 mutations are frequently found in cytogenetically normal acute myeloid leukemia, but in our analysis these mutations did not influence treatment outcome. (PMID:20421455)
• This study identified the IDH2 mutation status of a large series of gliomas analyzed by array-based comparative genomic hybridization (aCGH). We investigated whether the occurrence of IDH2 mutation correlates with 1p19q status. (PMID:20427748)
• O(6)-methylguanine DNA methyltransferase (MGMT) status, and mutations of isocitrate dehydrogenases 1 and 2 (IDH1/IDH2) are currently the three most pertinent markers in diffuse gliomas [Review] (PMID:20465388)
• IDH2 mutations are associated with myelodysplastic syndrome and acute myeloid leukemia. (PMID:20485375)
• IDH2 mutations are associated with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. (PMID:20508616)
• IDH1 and IDH2 mutations are relevant to the progression of gliomas, prognosis and treatment of patients with gliomas harboring the mutation [review] (PMID:20510884)
• In AML, IDH1 and IDH2 mutations are more common among AML with normal karyotype and NPM1(mutant) genotypes. (PMID:20538800)
• IDH1 and IDH2 mutations are recurring genetic changes in acute myeloid leukemia (AML); they constitute a poor prognostic factor in cytogenetically normal-AML with mutated NPM1 without FLT3-internal tandem duplication (PMID:20567020)
• Studies on the cell-lineages of tumors with IDH1/2 mutations may help clarify the role of these mutations in the development of brain tumors. (PMID:20603105)
• IDH2m were associated with a low WBC count at diagnosis and poor prognosis-lower response to chemotherapy and higher relapse and lower survival. (PMID:20625116)
• serum 2-hydroxyglutarate concentrations were substantially increased in AML patients with both IDH1 and IDH2 mutations (PMID:20659156)
• Mutations in IDH2 are associated with acute myeloid leukemias. (PMID:20678218)
• IDH1 and IDH2 mutations are associated glioma and acute myeloid leukemia cases.[Review] (PMID:20692206)
• Results suggested that the suppression of HIF-1alpha accumulation by IDPm knockdown in PC3 cells was due to an inhibition of HIF-1alpha transcription. (PMID:20713124)
• study detected heterozygous germline mutations in IDH2 that alter enzyme residue Arg(140) in 15 unrelated patients with d-2-hydroxyglutaric aciduria (PMID:20847235)
• a possible association between IDH mutations and trisomy 8 in myelodysplastic syndromes and acute myeloid leukemia. (PMID:20861910)
• Correlation between IDH2 mutations and disease status in acute myeloid leukemia. (PMID:20929316)
• IDH2 mutations in patients with acute myeloid leukemia: missense p.R140 mutations are linked to disease status. (PMID:20929327)
• The frequency of IDH1 and IDH2 missense mutations in Chinese AML patients reached 5.9% and 8.3%, respectively. (PMID:20946881)
• IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis. (PMID:20962862)
• review summarizes current understanding of the recently identified mutations in IDH1 and IDH2 and provide several potential molecular mechanisms linking them to malignant transformation [review] (PMID:20972461)
• IDH mutation appears to be a significant marker of positive prognosis and chemosensitivity in low-grade gliomas, independently of 1p-19q codeletion, whereas its impact on the course of untreated tumors seems to be limited. (PMID:20975057)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	idh2	ENSDARG00000003795
mus_musculus	Idh2	ENSMUSG00000030541
rattus_norvegicus	Idh2	ENSRNOG00000013949
caenorhabditis_elegans		WBGENE00007942

Paralogs (1): IDH1 (ENSG00000138413)

Protein

Protein identifiers

Isocitrate dehydrogenase [NADP], mitochondrial — P48735 (reviewed: P48735)

Alternative names: ICD-M, IDP, NADP(+)-specific ICDH, Oxalosuccinate decarboxylase

All UniProt accessions (3): P48735, H0YL11, H0YLL5

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion.

Post-translational modifications. Acetylation at Lys-413 dramatically reduces catalytic activity. Deacetylated by SIRT3.

Disease relevance. D-2-hydroxyglutaric aciduria 2 (D2HGA2) [MIM:613657] A neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine. The disease is caused by variants affecting the gene represented in this entry. Glioma (GLM) [MIM:137800] Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. The gene represented in this entry is involved in disease pathogenesis. enetic variations are associated with cartilaginous tumors such as enchondroma or chondrosarcoma.

Cofactor. Binds 1 Mg(2+) or Mn(2+) ion per subunit.

Similarity. Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Isoforms (2)

UniProt ID	Names	Canonical?
P48735-1	1	yes
P48735-2	2

RefSeq proteins (3): NP_001276839, NP_001277043, NP_002159* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004790	Isocitrate_DH_NADP	Family
IPR019818	IsoCit/isopropylmalate_DH_CS	Conserved_site
IPR024084	IsoPropMal-DH-like_dom	Domain

Pfam: PF00180

Enzyme classification (BRENDA):

• EC 1.1.1.42 — isocitrate dehydrogenase (NADP+) (BRENDA: 86 organisms, 105 substrates, 196 inhibitors, 459 Km, 184 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADP+	—	155
ISOCITRATE	0.0006–19	118
2-OXOGLUTARATE	0.017–12	38
DL-ISOCITRATE	0.0001–0.1243	31
MN2+	—	25
NAD+	0.001–47	21
D,L-ISOCITRATE	0.0017–0.118	18
NADPH	0.0007–0.04	18
MG2+	0.012–0.31	8
D-ISOCITRATE	0.028–0.239	7
CO2	0.2–13.82	5
(2R,3S)-ISOCITRATE	0.019–0.202	2
OXALOSUCCINATE	0.56–1.2	2

Catalyzed reactions (Rhea), 1 shown:

• D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH (RHEA:19629)

UniProt features (95 total): modified residue 29, helix 17, strand 14, binding site 11, sequence variant 10, turn 4, mutagenesis site 3, site 2, sequence conflict 2, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5I95	X-RAY DIFFRACTION	1.54
4JA8	X-RAY DIFFRACTION	1.55
5I96	X-RAY DIFFRACTION	1.55
5SVO	X-RAY DIFFRACTION	1.87
6UJ7	X-RAY DIFFRACTION	1.9
5GIS	X-RAY DIFFRACTION	1.93
6ADI	X-RAY DIFFRACTION	1.97
6VFZ	X-RAY DIFFRACTION	1.99
5SVN	X-RAY DIFFRACTION	2.1
6UJ8	X-RAY DIFFRACTION	2.25
6UJ9	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48735-F1	92.07	0.86

Antibody-complex structures (SAbDab): 2 — 5GIS, 6UJ9

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 179 (critical for catalysis); 251 (critical for catalysis)

Ligand- & substrate-binding residues (11): 314; 349–354; 367; 115–117; 117; 122; 134–140; 149; 172; 291; 299

Post-translational modifications (29): 45, 48, 67, 69, 80, 80, 106, 106, 155, 166, 166, 180, 180, 193, 193, 199, 256, 256, 263, 272 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
413	44-fold loss in activity.
413	20-fold decrease in vmax.
413	no appreciable difference in km for isocitrate and nadp.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-71403	Citric acid cycle (TCA cycle)
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-9854311	Maturation of TCA enzymes and regulation of TCA cycle

MSigDB gene sets: 527 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, RNGTGGGC_UNKNOWN, MODULE_93, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, GOBP_NADPPLUS_METABOLIC_PROCESS, GCANCTGNY_MYOD_Q6, MORF_HDAC1, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (10): carbohydrate metabolic process (GO:0005975), glyoxylate cycle (GO:0006097), tricarboxylic acid cycle (GO:0006099), isocitrate metabolic process (GO:0006102), 2-oxoglutarate metabolic process (GO:0006103), NADP+ metabolic process (GO:0006739), NADP+ biosynthetic process (GO:0006741), negative regulation of glial cell proliferation (GO:0060253), negative regulation of glial cell migration (GO:1903976), negative regulation of matrix metallopeptidase secretion (GO:1904465)

GO Molecular Function (6): magnesium ion binding (GO:0000287), isocitrate dehydrogenase (NADP+) activity (GO:0004450), NAD binding (GO:0051287), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), metal ion binding (GO:0046872)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), peroxisome (GO:0005777), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Mitochondrial biogenesis	1
Aerobic respiration and respiratory electron transport	1
Metabolism of proteins	1
Citric acid cycle (TCA cycle)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	2
cytoplasm	2
carbohydrate metabolic process	1
glyoxylate metabolic process	1
aerobic respiration	1
tricarboxylic acid metabolic process	1
secondary alcohol metabolic process	1
dicarboxylic acid metabolic process	1
purine nucleotide metabolic process	1
nicotinamide nucleotide metabolic process	1
purine nucleotide biosynthetic process	1
NADP+ metabolic process	1
nicotinamide nucleotide biosynthetic process	1
negative regulation of cell population proliferation	1
glial cell proliferation	1
negative regulation of gliogenesis	1
regulation of glial cell proliferation	1
glial cell migration	1
negative regulation of cell migration	1
regulation of glial cell migration	1
negative regulation of protein secretion	1
regulation of matrix metallopeptidase secretion	1
matrix metallopeptidase secretion	1
metal ion binding	1
isocitrate dehydrogenase [NAD(P)+] activity	1
adenyl nucleotide binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
cation binding	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
microbody	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

4527 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IDH2	MDH2	P40926	972
IDH2	IDH3A	P50213	954
IDH2	IDH3G	P51553	951
IDH2	CS	O75390	946
IDH2	D2HGDH	Q8N465	934
IDH2	ACO2	Q99798	932
IDH2	ACO1	P21399	912
IDH2	FH	P07954	907
IDH2	IDH3B	O43837	903
IDH2	NNT	Q13423	887
IDH2	MGMT	P16455	882
IDH2	L2HGDH	Q9H9P8	878
IDH2	TET2	Q6N021	872
IDH2	SIRT3	Q9NTG7	825
IDH2	ASXL1	Q8IXJ9	818

IntAct

138 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
INSRR	INSR	psi-mi:“MI:0914”(association)	0.650
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
NAPA	NBAS	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
KCMF1	IDH2	psi-mi:“MI:0914”(association)	0.530
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
HSCB	NDUFS8	psi-mi:“MI:0914”(association)	0.460
	IDH2	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
PYGL	IDH2	psi-mi:“MI:0915”(physical association)	0.370
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
KBTBD7	THOC2	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
FASTKD3	VWA8	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
COQ2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
CEBPD	EEF1D	psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350

BioGRID (247): IDH2 (Affinity Capture-MS), IDH2 (Affinity Capture-MS), IDH1 (Co-fractionation), IDH2 (Co-fractionation), IDH3A (Co-fractionation), IDH3B (Co-fractionation), IDH3G (Co-fractionation), IDH2 (Affinity Capture-MS), IDH2 (Synthetic Growth Defect), IDH2 (Affinity Capture-MS), IDH2 (Affinity Capture-MS), IDH2 (Affinity Capture-MS), IDH2 (Affinity Capture-MS), IDH2 (Affinity Capture-MS), IDH2 (Affinity Capture-MS)

ESM2 similar proteins: A0A096P8D3, B7G620, C5XNN6, O13285, O13294, O14254, O50078, O75874, O82392, O88844, P21954, P24571, P33198, P41562, P41939, P48735, P50215, P50217, P50218, P53982, P54071, P56574, P65098, P77947, P79089, P9WKL0, P9WKL1, Q00ZY2, Q017T9, Q04467, Q06197, Q07422, Q0JKD0, Q1D9V4, Q1K6I4, Q23695, Q40345, Q43827, Q4R502, Q5R9C5

Diamond homologs: A0A096P8D3, B7G620, O13285, O13294, O14254, O75874, O88844, P21954, P33198, P41562, P48735, P50215, P50217, P50218, P53982, P54071, P56574, P65098, P79089, P9WKL0, P9WKL1, Q04467, Q06197, Q40345, Q49Z13, Q4R502, Q5R9C5, Q6XUZ5, Q75JR2, Q75JR3, Q8LPJ5, Q9SLK0, Q9SRZ6, Q9XSG3, Q9Z2K8, Q9Z2K9, P24404, P41939, Q1MA50, Q2K2V0

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
SIRT3	up-regulates	IDH2	deacetylation
IDH2	“up-regulates quantity”	2-oxoglutarate(2-)	“chemical modification”
IDH2	“down-regulates quantity”	D-threo-isocitrate(3-)
SIRT5	“up-regulates activity”	IDH2	“catalytic activity”
D-threo-isocitrate(3-)	“up-regulates activity”	IDH2	“chemical activation”
ACAT1	“down-regulates activity”	IDH2	acetylation
FLT3	“down-regulates activity”	IDH2	phosphorylation
CyclinA2/CDK2	“down-regulates quantity by destabilization”	IDH2	phosphorylation
GUCY1A2-B2	“down-regulates quantity by destabilization”	IDH2	ubiquitination
SKP2	“down-regulates quantity by destabilization”	IDH2	ubiquitination

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

IDH2 mutations have been observed in a number of cancer types, including sarcomas, hematologic malignancies, colon cancer and brain cancer. Mutations in the two isocitrate dehydrogenase enzymes involved in cytoplasmic (IDH1) and mitochondrial (IDH2) conversion of alpha-ketoglutarate to D-2-hydroxyglutarate have been described as mutually exclusive in many of these cancer types. The most frequent mutations involve R132 (IDH1) and R172 (IDH2) involve the active site and result in neomorphic enzyme activity. Although IDH2 (R172) mutations are associated with poorer overall prognosis in AML patients, its utility as a prognostic marker in MDS is still under debate.

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — AML, BLCA, CHOL, LGGNOS, OS.

Clinical variants and AI predictions

ClinVar

294 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	152
Likely benign	78
Benign	31

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
14717	NM_002168.4(IDH2):c.418C>G (p.Arg140Gly)	Pathogenic
2691259	NM_002168.4(IDH2):c.516G>T (p.Arg172Ser)	Pathogenic
376439	NM_002168.4(IDH2):c.514A>G (p.Arg172Gly)	Likely pathogenic
427064	NM_002168.4(IDH2):c.1288C>T (p.His430Tyr)	Likely pathogenic
828158	NM_002168.4(IDH2):c.1039G>A (p.Ala347Thr)	Likely pathogenic

SpliceAI

1747 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90084349:TCACA:T	acceptor_gain	1.0000
15:90084350:CACA:C	acceptor_gain	1.0000
15:90084350:CACAC:C	acceptor_gain	1.0000
15:90084351:ACA:A	acceptor_gain	1.0000
15:90084352:CA:C	acceptor_gain	1.0000
15:90084352:CAC:C	acceptor_gain	1.0000
15:90084353:AC:A	acceptor_loss	1.0000
15:90084354:C:CA	acceptor_loss	1.0000
15:90084354:C:CC	acceptor_gain	1.0000
15:90084357:C:CT	acceptor_gain	1.0000
15:90084813:CACTT:C	donor_loss	1.0000
15:90084814:A:AC	donor_gain	1.0000
15:90084814:ACT:A	donor_loss	1.0000
15:90084815:C:CT	donor_gain	1.0000
15:90084815:CTTG:C	donor_gain	1.0000
15:90084818:G:A	donor_gain	1.0000
15:90084846:T:TA	donor_gain	1.0000
15:90084904:CAAAC:C	acceptor_gain	1.0000
15:90084907:AC:A	acceptor_gain	1.0000
15:90084908:CC:C	acceptor_gain	1.0000
15:90084909:C:CC	acceptor_gain	1.0000
15:90084996:CTCA:C	donor_loss	1.0000
15:90084997:TCACC:T	donor_loss	1.0000
15:90084998:CACC:C	donor_loss	1.0000
15:90084999:A:AC	donor_gain	1.0000
15:90084999:ACCTG:A	donor_loss	1.0000
15:90085000:C:CC	donor_gain	1.0000
15:90085094:CGGCC:C	acceptor_gain	1.0000
15:90085096:GCCCT:G	acceptor_loss	1.0000
15:90085097:CC:C	acceptor_gain	1.0000

AlphaMissense

3000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90085066:G:C	S371R	1.000
15:90085066:G:T	S371R	1.000
15:90085068:T:G	S371R	1.000
15:90085309:C:T	G349E	1.000
15:90087125:G:C	D318E	1.000
15:90087125:G:T	D318E	1.000
15:90087126:T:A	D318V	1.000
15:90087126:T:C	D318G	1.000
15:90087126:T:G	D318A	1.000
15:90087127:C:A	D318Y	1.000
15:90087127:C:G	D318H	1.000
15:90087137:A:C	D314E	1.000
15:90087137:A:T	D314E	1.000
15:90087138:T:A	D314V	1.000
15:90087138:T:C	D314G	1.000
15:90087138:T:G	D314A	1.000
15:90087139:C:G	D314H	1.000
15:90087141:C:T	G313E	1.000
15:90087149:G:C	N310K	1.000
15:90087149:G:T	N310K	1.000
15:90087205:C:G	D292H	1.000
15:90087206:A:C	D291E	1.000
15:90087206:A:T	D291E	1.000
15:90087207:T:A	D291V	1.000
15:90087207:T:G	D291A	1.000
15:90087208:C:G	D291H	1.000
15:90087216:C:G	R288P	1.000
15:90087478:T:A	D259V	1.000
15:90087493:A:T	I254K	1.000
15:90087501:C:A	K251N	1.000

dbSNP variants (sampled 300 via entrez): RS1000001798 (15:90084610 GCT>G), RS1000133962 (15:90083265 T>G), RS1000272961 (15:90088691 C>A,G,T), RS1000394932 (15:90083054 T>C,G), RS1000446999 (15:90082837 G>A,C), RS1000628586 (15:90103682 G>A,T), RS1000926843 (15:90097450 C>T), RS1000947282 (15:90090832 G>A), RS1001004892 (15:90101377 G>A), RS1001006554 (15:90092352 T>C), RS1001164346 (15:90097715 C>T), RS1001246952 (15:90087998 T>C), RS1001279522 (15:90095894 C>G), RS1001532695 (15:90096360 T>C), RS1001597600 (15:90102190 G>A,C)

Disease associations

OMIM: gene MIM:147650 | disease phenotypes: MIM:613657, MIM:166000, MIM:153100, MIM:614569

GenCC curated gene-disease

Disease	Classification	Inheritance
d-2-hydroxyglutaric aciduria 2	Strong	Autosomal dominant
D-2-hydroxyglutaric aciduria	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AD

Mondo (10): d-2-hydroxyglutaric aciduria 2 (MONDO:0013345), Ollier disease (MONDO:0008145), teratoma (MONDO:0002601), lymphatic malformation (MONDO:0019313), vascular malformation (MONDO:0024291), acute myocardial infarction (MONDO:0004781), Maffucci syndrome (MONDO:0013808), mitochondrial disease (MONDO:0044970), cleft palate (MONDO:0016064), D-2-hydroxyglutaric aciduria (MONDO:0010924)

Orphanet (5): D-2-hydroxyglutaric aciduria (Orphanet:79315), Ollier disease (Orphanet:296), Maffucci syndrome (Orphanet:163634), Mitochondrial disease (Orphanet:68380), Cleft palate (Orphanet:2014)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000324	Facial asymmetry
HP:0000750	Delayed speech and language development
HP:0000853	Goiter
HP:0000944	Abnormal metaphysis morphology
HP:0001028	Hemangioma
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001298	Encephalopathy
HP:0001387	Joint stiffness
HP:0001482	Subcutaneous nodule
HP:0001510	Growth delay
HP:0001638	Cardiomyopathy
HP:0002015	Dysphagia
HP:0002119	Ventriculomegaly
HP:0002650	Scoliosis
HP:0002653	Bone pain
HP:0002664	Neoplasm
HP:0002756	Pathologic fracture
HP:0002757	Recurrent fractures
HP:0002763	Abnormal cartilage morphology
HP:0002797	Osteolysis
HP:0002857	Genu valgum
HP:0002893	Pituitary adenoma
HP:0002897	Parathyroid adenoma
HP:0002967	Cubitus valgus
HP:0002970	Genu varum
HP:0002983	Micromelia
HP:0003002	Breast carcinoma

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003134_16	Cerebrospinal fluid clusterin levels	6.000000e-06
GCST007096_28	Pulse pressure	4.000000e-08
GCST007269_286	Pulse pressure	8.000000e-10
GCST008971_141	Urate levels	8.000000e-06
GCST008972_212	Urate levels	2.000000e-08
GCST012338_33	Gout	5.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004531	urate measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D013724	Teratoma	C04.557.465.910
D054079	Vascular Malformations	C14.240.850; C16.131.240.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3991501 (SINGLE PROTEIN), CHEMBL4523659 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,645 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3989908	ENASIDENIB	4	2,315
CHEMBL3989931	ENASIDENIB MESYLATE	4	1,311
CHEMBL3989958	IVOSIDENIB	4	2,231
CHEMBL4279047	VORASIDENIB	4	504
CHEMBL4297610	OLUTASIDENIB	4	235
CHEMBL6000618	CRELOSIDENIB	2	48
CHEMBL6068069	RANOSIDENIB	2	1

Clinical evidence (CIViC)

Drug × variant × indication: 5 predictive associations from 6 curated evidence items; also 15 prognostic, 1 diagnostic.

Variant	Therapy	Indication	Effect	Level	CIViC
IDH2 Mutation	Enasidenib	Acute Myeloid Leukemia	Sensitivity/Response	CIViC A	EID5069 +1
IDH2 Mutation OR IDH1 Mutation	Vorasidenib	Glioma	Sensitivity/Response	CIViC A	EID11708
IDH2 R172K OR IDH2 R172G OR IDH2 R172W	Vorasidenib	Low Grade Glioma	Sensitivity/Response	CIViC A	EID11509
IDH2 Mutation	Venetoclax	Acute Myeloid Leukemia	Sensitivity/Response	CIViC C	EID8857
IDH2 R140	Enasidenib	Acute Myeloid Leukemia	Sensitivity/Response	CIViC D	EID10292

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.1.1.42 Isocitrate dehydrogenases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
LY3410738	Inhibition	6.05	pIC50

Binding affinities (BindingDB)

366 measured of 525 human assays (525 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
GSK321	IC50	3.8 nM
N-cyclopropyl-2,2-difluoro-2-[4-thiophen-3-yl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]acetamide	IC50	14.2 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
2,2-difluoro-N-(oxetan-3-yl)-2-[4-thiophen-3-yl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]acetamide	IC50	29.5 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
2,2-difluoro-2-[4-thiophen-3-yl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]-N-(2,2,2-trifluoroethyl)acetamide	IC50	45.5 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
N-cyclopropyl-2,2-difluoro-2-[4-phenyl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]acetamide	IC50	53.8 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
N-[[4-thiophen-3-yl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]methyl]cyclopropanecarboxamide	IC50	55 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
N-(1-cyanocyclopropyl)-2,2-difluoro-2-[4-thiophen-3-yl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]acetamide	IC50	56.5 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
2,2-difluoro-N-propan-2-yl-2-[4-thiophen-3-yl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]acetamide	IC50	62.4 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
N-cyclopropyl-2-methyl-2-[4-thiophen-3-yl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]propanamide	IC50	65.7 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
N-cyclopropyl-2-[4-thiophen-3-yl-3-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenyl]propanamide	IC50	69.9 nM	US-10155722: Antitumor compound targeting IDH2 mutation and method of use thereof
BDBM279926	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
3-[4,6-bis[[(1R)-1-cyclopropylethyl]amino]-1,3,5-triazin-2-yl]phenol	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-[(1R)-1-cyclopropylethyl]-4-N-[(1S)-1-phenylethyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10172864: Therapeutically active compounds and their methods of use
4-N-(2-methylpropyl)-2-N-(oxan-4-yl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N,4-N-bis[(1R)-1-cyclopropylethyl]-6-[3-(trifluoromethyl)pyrazol-1-yl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10172864: Therapeutically active compounds and their methods of use
2-N,4-N-bis(3,3-difluorocyclobutyl)-6-[6-(trifluoromethyl)pyrazin-2-yl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-(3,3-difluorocyclopentyl)-4-N-[2-(1,1-difluoroethyl)-4-pyridinyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
6-(6-amino-3-fluoro-2-pyridinyl)-2-N-(4,4-difluorocyclohexyl)-4-N-(3,5-difluorophenyl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-(3,3-difluorocyclobutyl)-4-N-[2-(1-isocyanocyclopropyl)-4-pyridinyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
4-N-[2-(trifluoromethyl)-4-pyridinyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-2-N-(1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-[(1S)-3,3-difluorocyclopentyl]-4-N-[2-(1-isocyanocyclopropyl)-4-pyridinyl]-6-[3-(trifluoromethyl)pyrazol-1-yl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10172864: Therapeutically active compounds and their methods of use
4-N-(cyclopropylmethyl)-2-N-(3-fluoro-5-isocyanophenyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
6-[3-(trifluoromethyl)pyrazol-1-yl]-4-N-[2-(trifluoromethyl)-4-pyridinyl]-2-N-(1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
4-N-[(1R)-1-cyclopropylethyl]-2-N-(dicyclopropylmethyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10172864: Therapeutically active compounds and their methods of use
2-N-(3,3-difluorocyclobutyl)-4-N-(3,5-difluorophenyl)-6-(3,6-difluoro-2-pyridinyl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
6-(6-chloro-2-pyridinyl)-4-N-(cyclopropylmethyl)-2-N-[2-(trifluoromethyl)-4-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
4-N-[2-(1-isocyanocyclopropyl)-4-pyridinyl]-6-[3-(trifluoromethyl)pyrazol-1-yl]-2-N-(1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
4-[[4-[3-(trifluoromethyl)pyrazol-1-yl]-6-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]-1,3,5-triazin-2-yl]amino]pyridine-2-carbonitrile	IC50	75 nM	US-10172864: Therapeutically active compounds and their methods of use
4-[[4-[(3,3-difluorocyclobutyl)amino]-6-[3-(trifluoromethyl)pyrazol-1-yl]-1,3,5-triazin-2-yl]amino]pyridine-2-carbonitrile	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
6-(6-chloro-2-pyridinyl)-2-N-[2-(1-isocyanocyclopropyl)-4-pyridinyl]-4-N-(2,2,2-trifluoroethyl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
4-N-(2-phenyl-4-pyridinyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-2-N-(1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-(4,4-difluorocyclohexyl)-4-N-(2-phenyl-4-pyridinyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
4-N-(3,3-difluorocyclopentyl)-2-N-(1-pyridin-2-ylpyrrolidin-3-yl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N,4-N-bis(4,4-difluorocyclohexyl)-6-[2-(trifluoromethyl)-1,3-thiazol-4-yl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-[2-(1-isocyanocyclopropyl)-4-pyridinyl]-4-N-(2,2,2-trifluoroethyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
4-N-(3,3-difluorocyclopentyl)-2-N-(1-pyrimidin-2-ylpyrrolidin-3-yl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-(2,2-difluorospiro[3.3]heptan-6-yl)-4-N-[2-(1-isocyanocyclopropyl)-4-pyridinyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
3-[[4-[[2-(1,1-difluoroethyl)-4-pyridinyl]amino]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazin-2-yl]amino]-3-methylbutanenitrile	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-[[4-[[2-(1,1-difluoroethyl)-4-pyridinyl]amino]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazin-2-yl]amino]-2-methylpropanenitrile	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
6-(6-amino-3-fluoro-2-pyridinyl)-2-N,4-N-bis(4,4-difluorocyclohexyl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N,4-N-bis(3,3-difluorocyclobutyl)-6-[4-(trifluoromethyl)pyrimidin-2-yl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-(4,4-difluorocyclohexyl)-4-N-(3,5-difluorophenyl)-6-(3,6-difluoro-2-pyridinyl)-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
1-[4-[[4-[(3,3-difluorocyclopentyl)amino]-6-[4-(trifluoromethyl)pyrimidin-2-yl]-1,3,5-triazin-2-yl]amino]-2-pyridinyl]cyclopropane-1-carbonitrile	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
6-[2-(trifluoromethyl)pyrimidin-4-yl]-2-N,4-N-bis[(2R)-1,1,1-trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10172864: Therapeutically active compounds and their methods of use
1-[4-[[4-[[(1R)-3,3-difluorocyclopentyl]amino]-6-[3-(trifluoromethyl)pyrazol-1-yl]-1,3,5-triazin-2-yl]amino]-2-pyridinyl]cyclopropane-1-carbonitrile	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N,4-N-bis[(2,2-difluorocyclopropyl)methyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N,4-N-bis(4,4-difluorocyclohexyl)-6-[4-(1,1-difluoroethyl)-1,3-thiazol-2-yl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
2-N-(4,4-difluorocyclohexyl)-4-N-[2-(1,1-difluoroethyl)-4-pyridinyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
1-[4-[[4-[(2,2-difluorocyclopropyl)methylamino]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazin-2-yl]amino]-2-pyridinyl]cyclopropane-1-carbonitrile	IC50	75 nM	US-10028961: Therapeutically active compounds and their methods of use
4-N-[2-(4-chlorophenyl)-4-pyridinyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-2-N-[(2R)-1,1,1-trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine	IC50	75 nM	US-10172864: Therapeutically active compounds and their methods of use

ChEMBL bioactivities

741 potent at pChembl≥5 of 764 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.73	Kd	1.871	nM	CHEMBL3752910
8.73	ED50	1.871	nM	CHEMBL3752910
8.52	IC50	3	nM	CHEMBL4280772
8.40	IC50	4	nM	CHEMBL4278420
8.32	IC50	4.78	nM	CHEMBL5415614
8.22	IC50	6	nM	CHEMBL4463644
8.22	IC50	6	nM	CHEMBL4439421
8.22	IC50	6	nM	CHEMBL4280132
8.21	IC50	6.1	nM	CHEMBL4753099
8.15	IC50	7	nM	VORASIDENIB
8.15	IC50	7	nM	CHEMBL4278845
8.15	IC50	7	nM	CHEMBL5405494
8.10	IC50	8	nM	CHEMBL4283785
8.10	IC50	8	nM	CHEMBL5428697
8.05	IC50	9	nM	ENASIDENIB
8.05	IC50	9	nM	CHEMBL4277352
8.05	IC50	9	nM	CHEMBL4288840
8.05	IC50	9	nM	CHEMBL5430339
8.02	IC50	9.6	nM	CHEMBL4787510
8.00	IC50	10	nM	CHEMBL5441137
7.96	IC50	11	nM	ENASIDENIB
7.91	IC50	12.2	nM	CHEMBL4800354
7.89	IC50	13	nM	CHEMBL4292293
7.89	IC50	13	nM	CHEMBL4280772
7.86	IC50	13.8	nM	CHEMBL4796025
7.85	IC50	14	nM	CHEMBL4278828
7.85	IC50	14	nM	CHEMBL4282989
7.85	IC50	14.2	nM	CHEMBL5857739
7.81	IC50	15.5	nM	CHEMBL4754521
7.80	IC50	16	nM	CHEMBL4280772
7.80	IC50	16	nM	CHEMBL4277352
7.80	IC50	16	nM	CHEMBL6142043
7.76	IC50	17.4	nM	CHEMBL4786020
7.76	IC50	17.4	nM	CHEMBL4796025
7.75	IC50	17.7	nM	CHEMBL4762400
7.74	IC50	18.4	nM	CHEMBL4753744
7.73	IC50	18.6	nM	CHEMBL4783076
7.72	IC50	19	nM	CHEMBL4448857
7.70	IC50	19.9	nM	CHEMBL4782070
7.68	IC50	21	nM	CHEMBL5428697
7.68	IC50	21	nM	CHEMBL6147051
7.68	IC50	21	nM	CHEMBL6165219
7.66	IC50	22	nM	CHEMBL4278828
7.66	IC50	22	nM	CHEMBL4292293
7.66	IC50	22	nM	CHEMBL4289692
7.65	IC50	22.2	nM	CHEMBL4746278
7.64	IC50	23	nM	CHEMBL3392845
7.64	IC50	23	nM	CHEMBL5397750
7.64	IC50	23	nM	CHEMBL6147083
7.62	IC50	24	nM	CHEMBL5433752

PubChem BioAssay actives

236 with measured affinity, of 438 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148570: Binding affinity to human IDH2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0019	uM
2-N,4-N-bis(3,3-difluorocyclobutyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0030	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis[(1R)-1-cyclopropylethyl]-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0040	uM
(3S)-3-(trifluoromethyl)-1-[4-[6-(trifluoromethyl)-2-pyridinyl]-6-[[2-(trifluoromethyl)-4-pyridinyl]amino]-1,3,5-triazin-2-yl]pyrrolidin-3-ol	2014784: Inhibition of IDH2 R140Q mutant (unknown origin)	ic50	0.0048	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis(3,3-difluorocyclopentyl)-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0060	uM
(4R)-3-[2-[[(1S)-1-[1-(4-chlorophenyl)imidazol-4-yl]ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-4-[(1S)-1-fluoroethyl]-1,3-oxazolidin-2-one	1513097: Inhibition of IDH2 R172K mutant (unknown origin) using alpha-KG as substrate after 90 mins in presence of NADPH by RF/MS analysis	ic50	0.0060	uM
(4S)-3-[2-[[(1R)-1-[4-methyl-5-[2-(trifluoromethyl)-4-pyridinyl]-2-pyridinyl]ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-4-propan-2-yl-1,3-oxazolidin-2-one	1513097: Inhibition of IDH2 R172K mutant (unknown origin) using alpha-KG as substrate after 90 mins in presence of NADPH by RF/MS analysis	ic50	0.0060	uM
17-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-2,4,6,8,20-pentazatricyclo[13.3.1.13,7]icosa-1(19),3,5,7(20),15,17-hexaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0061	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis[(2S)-1,1,1-trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0070	uM
Vorasidenib	1513091: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in 2-HG levels after 90 mins in presence of NADPH by resazurin-based assay	ic50	0.0070	uM
3-[[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]amino]propane-1,2-diol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0070	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis(1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0080	uM
2-[[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]amino]propane-1,3-diol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0080	uM
(2S)-3-[[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]amino]propane-1,2-diol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0090	uM
2-N,4-N-bis(3,3-difluorocyclopentyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0090	uM
Enasidenib	1541882: Inhibition of full-length C-terminal His6 tagged IDH2 R140Q mutant (1 to 452 residues) (unknown origin) homodimer expressed in Sf9 cells assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 16 hrs followed by substrate addition and measured after 1 hr by Diaphorase/Resazurin dye based fluorescence assay	ic50	0.0090	uM
2-N,4-N-bis(4,4-difluorocyclohexyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0090	uM
10,10-dimethyl-18-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-11-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(20),3,5,7(21),16,18-hexaene	1703360: Inhibition of IDH2 R172K mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0096	uM
1-[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]pyrrolidin-3-ol	2014793: Inhibition of IDH2 R140Q mutant (unknown origin) expressed in human TF-1 cells assessed as inhibition of D2HG production incubated for 3 days by UHPL HRMS analysis	ic50	0.0100	uM
18-chloro-5-[6-(trifluoromethyl)-2-pyridinyl]-11-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(19),3,5,7(21),16(20),17-hexaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0122	uM
2-N,4-N-bis(cyclopropylmethyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541882: Inhibition of full-length C-terminal His6 tagged IDH2 R140Q mutant (1 to 452 residues) (unknown origin) homodimer expressed in Sf9 cells assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 16 hrs followed by substrate addition and measured after 1 hr by Diaphorase/Resazurin dye based fluorescence assay	ic50	0.0130	uM
(12E)-17-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-2,4,6,8,20-pentazatricyclo[13.3.1.13,7]icosa-1(19),3,5,7(20),12,15,17-heptaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0138	uM
2-N,4-N-bis[(1R)-1-cyclopropylethyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0140	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis(1-cyclopropylpropyl)-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0140	uM
4-N-(2-methyl-2-prop-2-enoxypropyl)-2-N-[3-(trifluoromethyl)phenyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1703360: Inhibition of IDH2 R172K mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0155	uM
(12Z)-18-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-15-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(20),3,5,7(21),12,16,18-heptaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0174	uM
10-methyl-18-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-11-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(20),3,5,7(21),16,18-hexaene	1703360: Inhibition of IDH2 R172K mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0177	uM
(11Z)-17-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-14-oxa-2,4,6,8,20-pentazatricyclo[13.3.1.13,7]icosa-1(19),3,5,7(20),11,15,17-heptaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0184	uM
18-fluoro-5-[6-(trifluoromethyl)-2-pyridinyl]-11-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(19),3,5,7(21),16(20),17-hexaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0186	uM
2-N-propan-2-yl-4-N-[2-(trifluoromethyl)-4-pyridinyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541882: Inhibition of full-length C-terminal His6 tagged IDH2 R140Q mutant (1 to 452 residues) (unknown origin) homodimer expressed in Sf9 cells assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 16 hrs followed by substrate addition and measured after 1 hr by Diaphorase/Resazurin dye based fluorescence assay	ic50	0.0190	uM
18-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(20),3,5,7(21),16,18-hexaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0199	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis(4,4-difluorocyclohexyl)-1,3,5-triazine-2,4-diamine	1541885: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0220	uM
18-methyl-5-[6-(trifluoromethyl)-2-pyridinyl]-11-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(19),3,5,7(21),16(20),17-hexaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0222	uM
1-[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]piperidin-3-ol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0230	uM
1-[5-(cyclopropylsulfamoyl)-2-thiophen-3-ylphenyl]-3-[3-(trifluoromethyl)phenyl]urea	2014784: Inhibition of IDH2 R140Q mutant (unknown origin)	ic50	0.0230	uM
(3R)-1-[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]piperidin-3-ol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0240	uM
(3S)-1-[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]piperidin-3-ol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0250	uM
2-methyl-1-[[4-[3-(trifluoromethyl)anilino]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazin-2-yl]amino]propan-2-ol	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0260	uM
10,10-dimethyl-18-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-11,15-dioxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(20),3,5,7(21),16,18-hexaene	1703360: Inhibition of IDH2 R172K mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0274	uM
(13Z)-18-fluoro-5-[6-(trifluoromethyl)-2-pyridinyl]-11-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(19),3,5,7(21),13,16(20),17-heptaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0295	uM
(2R)-3-[[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]amino]propane-1,2-diol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0310	uM
2-N-[(2-methylpropan-2-yl)oxy]-4-N-[2-(trifluoromethyl)-4-pyridinyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1513083: Inhibition of IDH2 R172K mutant (40 to end residues) (unknown origin) using alpha-KG as substrate after 120 mins in presence of NADPH by resazurin-based assay	ic50	0.0317	uM
1-[4,6-bis[3-(trifluoromethyl)anilino]-1,3,5-triazin-2-yl]piperidin-4-ol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0320	uM
(13Z)-18-chloro-5-[6-(trifluoromethyl)-2-pyridinyl]-11-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(19),3,5,7(21),13,16(20),17-heptaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0360	uM
6-N-methyl-2-N,4-N-bis[3-(trifluoromethyl)phenyl]-1,3,5-triazine-2,4,6-triamine	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0370	uM
19-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-2,4,6,8,22-pentazatricyclo[15.3.1.13,7]docosa-1(21),3,5,7(22),17,19-hexaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0372	uM
(13E)-18-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(20),3,5,7(21),13,16,18-heptaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0376	uM
(14E)-19-(trifluoromethyl)-5-[6-(trifluoromethyl)-2-pyridinyl]-2,4,6,8,22-pentazatricyclo[15.3.1.13,7]docosa-1(21),3,5,7(22),14,17,19-heptaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0376	uM
(13Z)-18-methyl-5-[6-(trifluoromethyl)-2-pyridinyl]-11-oxa-2,4,6,8,21-pentazatricyclo[14.3.1.13,7]henicosa-1(19),3,5,7(21),13,16(20),17-heptaene	1703359: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay	ic50	0.0379	uM
(3R)-1-[4-[3-(trifluoromethyl)anilino]-6-[[6-(trifluoromethyl)-2-pyridinyl]amino]-1,3,5-triazin-2-yl]pyrrolidin-3-ol	2014788: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate incubated for 16 hrs in the presence of NADPH by absorbance based plate reader analysis	ic50	0.0380	uM

CTD chemical–gene interactions

87 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects splicing, decreases expression	4
Valproic Acid	increases methylation, decreases expression, increases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
Tobacco Smoke Pollution	decreases expression	3
Cyclosporine	decreases expression	3
cobaltous chloride	decreases expression	2
bisphenol S	increases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Zoledronic Acid	decreases expression, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Cisplatin	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tamoxifen	affects expression, affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tunicamycin	decreases expression, increases expression	2
Paclitaxel	affects response to substance, decreases expression	2
Raloxifene Hydrochloride	affects reaction, increases expression, affects expression, affects cotreatment	2
bisphenol F	increases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
sodium arsenate	decreases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
arsenite	affects binding, decreases reaction	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
nickel chloride	increases activity	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
periodate-oxidized adenosine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
glycidamide	decreases expression	1

ChEMBL screening assays

84 unique, capped per target: 84 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4135757	Binding	Inhibition of IDH2 R172K mutant (unknown origin) expressed in human HCT116 cells assessed as reduction in 2-HG level	Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor. — ACS Med Chem Lett

Cellosaurus cell lines

33 cell lines: 27 cancer cell line, 6 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0543	SW1353	Cancer cell line	Female
CVCL_3090	OUMS-27	Cancer cell line	Male
CVCL_9921	ch-2879	Cancer cell line	Female
CVCL_A4BL	TF-1 IDH2 p.R140Q-Luc2	Cancer cell line	Male
CVCL_B042	C3842	Cancer cell line	Male
CVCL_B7VD	Abcam Jurkat IDH2 KO	Cancer cell line	Male
CVCL_B8HT	Abcam HCT 116 IDH2 KO	Cancer cell line	Male
CVCL_B8X1	Abcam MCF-7 IDH2 KO	Cancer cell line	Female
CVCL_B9K3	Abcam A-549 IDH2 KO	Cancer cell line	Male
CVCL_D3D8	CHO/IDH2-R172K	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04999618	PHASE4	COMPLETED	A New Approach in Laser Surgery Using the Regenerative Solution in Children Diagnosed With Vascular Pathology
NCT00157768	PHASE4	COMPLETED	IRIS : Use of Implantable Defibrillator in High-risk Patients Early After Acute Myocardial Infarction
NCT00178620	PHASE4	COMPLETED	Pre-hospital Administration of Thrombolytic Therapy With Urgent Culprit Artery Revascularization
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00222573	PHASE4	COMPLETED	Efficacy and Safety of Adding Clopidogrel to Aspirin or Use of Metoprolol in Myocardial Infarction
NCT00257153	PHASE4	COMPLETED	Thrombus Aspiration Before Standard Primary Angioplasty Improves Myocardial Reperfusion in Acute Myocardial Infarction.
NCT00257309	PHASE4	TERMINATED	Thrombolysis Versus Primary Angioplasty for AMI in Elderly Patients
NCT00288665	PHASE4	COMPLETED	Thrombectomy and Improvement of Left Ventricular Function in AMI
NCT00300833	PHASE4	UNKNOWN	Treating Acute MI Patients With Aggrastat on Their Way to Hospital
NCT00302419	PHASE4	COMPLETED	Effect of Complementary Intracoronary Streptokinase Administration Immediately After Primary Percutaneous Coronary Intervention on Microvascular Perfusion and Late Term Infarct Size in Patients With Acute Myocardial Infarction
NCT00362778	PHASE4	COMPLETED	Intensive Insulin Therapy in Non-diabetic Patients With Acute Myocardial Infarction and Hyperglycaemia
NCT00383136	PHASE4	COMPLETED	FATA: Randomized Study on Facilitated Angioplasty With Tirofiban or Abciximab
NCT00423020	PHASE4	UNKNOWN	Anti-Restenosis After AMI by Erythropoietin
NCT00536887	PHASE4	COMPLETED	Effects of Atorvastatin 10 mg Versus 40 mg in Eight Months Follow-up Coronary Flow Reserve and Bone Marrow Stem Cell Mobilization in Patients With Acute Myocardial Infarction
NCT00538317	PHASE4	COMPLETED	GPIIbIIIa Inhibitors in the RESCUe and RESURCOR Networks at the Acute Myocardial Infarction
NCT00611169	PHASE4	COMPLETED	The Effects of Facilitated Percutaeous Coronary Intervention in Acute Myocardial Infarction
NCT00627809	PHASE4	COMPLETED	Effect of Adjunctive Intracoronary Streptokinase on Late Term Left Ventricular Infarct Size and Volumes in Patients With Acute Myocardial Infarction
NCT00683111	PHASE4	COMPLETED	Prevention of Gastrointestinal Bleeding in Patients With Severe Ischemic Heart Disease
NCT00688922	PHASE4	UNKNOWN	Pravastatin for Acute Myocardial Infarction With Minimally to Mildly Increased Levels of Serum Cholesterol Study
NCT00692718	PHASE4	UNKNOWN	N-3 Fatty Acids for the Prevention of Atrial Fibrillation in Patients With Acute Heart Failure
NCT00712894	PHASE4	COMPLETED	Effects of Different Vasodilators on Coronary No-reflow During primAry percuTaneous Coronary intErvention in Patients With Acute Myocardial Infarction
NCT00766740	PHASE4	COMPLETED	Long Term Clinical Efficacy of Thrombectomy Devices in Acute ST Elevation Myocardial Infarction
NCT00806403	PHASE4	COMPLETED	Comparison Between Thrombolysis and Primary Percutaneous Coronary Intervention (PCI) to Treat ST-Segment Elevation Myocardial Infarction
NCT00827788	PHASE4	COMPLETED	Comparison Between Iso-Osmolar and Ipo-Osmolar Contrast Agents in Patients With Acute Myocardial Infarction (AMI) Undergoing Primary Percutaneous Coronary Intervention (PCI)
NCT00833612	PHASE4	COMPLETED	Counterpulsation Reduces Infarct Size Pre-PCI for AMI
NCT00882466	PHASE4	COMPLETED	The Effect of Erythropoietin at the Time of Reperfusion in Acute Myocardial Infarction
NCT00882739	PHASE4	COMPLETED	Safety and Efficacy of Three Different Loading Doses of Clopidogrel, in Patients With Acute Myocardial Infarction
NCT00986050	PHASE4	COMPLETED	Comparison of Drug Eluting and Bare Metal Stents With or Without Abciximab in ST Elevation Myocardial Infarction
NCT01050348	PHASE4	COMPLETED	To Investigate the Role of Upstream High Dose Statin in STEMI
NCT01062516	PHASE4	COMPLETED	Influence of Esomeprazole on Antiplatelet Action of Clopidogrel Associated With Aspirin
NCT01124890	PHASE4	COMPLETED	Southwest German Interventional Study in Acute Myocardial Infarction III
NCT01156662	PHASE4	UNKNOWN	Efficacy of Thrombosuction in Primary Percutaneous Coronary Intervention of Acute Myocardial Infarction
NCT01261832	PHASE4	UNKNOWN	Efficacy and Safety of Adjunctive Cilostazol in Acute Myocardial Infarction Patients
NCT01377207	PHASE4	COMPLETED	Optical Coherence Tomography Assessment of Gender diVersity In Primary Angioplasty. The OCTAVIA Trial
NCT01381185	PHASE4	COMPLETED	REsistance to Aspirin and Clopidogrel in acuTe Myocardial Infarction
NCT01404507	PHASE4	COMPLETED	Efficacy of Combination of IntraCoronary Bolus Abciximab and Aspiration Thrombectomy in STEMI
NCT01501110	PHASE4	COMPLETED	Effects of N-acetylcysteine on Low T3 Syndrome
NCT01636180	PHASE4	WITHDRAWN	Effect of the Repeated Loading Dose of Clopidogrel and High Dose of Clopidogrel Continuous Therapy on the Platelet Aggregation Inhibition in Patients With Myocardial Infarction Undergoing Interventional Treatment.
NCT01684982	PHASE4	COMPLETED	Everolimus Stent in Myocardial Infarction
NCT01696110	PHASE4	COMPLETED	BivaliRudin in Acute Myocardial Infarction vs Glycoprotein IIb/IIIa and Heparin :a Randomised Controlled Trial.