IDH1

Summary

IDH1 (isocitrate dehydrogenase (NADP(+)) 1, HGNC:5382) is a protein-coding gene on chromosome 2q34, encoding Isocitrate dehydrogenase [NADP] cytoplasmic (O75874). Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase. In precision oncology, IDH1 Mutation confers sensitivity to Ivosidenib + Azacitidine in Acute Myeloid Leukemia (CIViC Level A); 24 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 cytoplasm and peroxisomes. It contains the PTS-1 peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production. Alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 3417 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Maffucci syndrome (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 490 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 111
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 25 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 15 cancer types
• MANE Select transcript: NM_005896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5382
Approved symbol	IDH1
Name	isocitrate dehydrogenase (NADP(+)) 1
Location	2q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138413
Ensembl biotype	protein_coding
OMIM	147700
Entrez	3417

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 31 protein_coding, 3 retained_intron

ENST00000345146, ENST00000415282, ENST00000415913, ENST00000417583, ENST00000446179, ENST00000451391, ENST00000462386, ENST00000481557, ENST00000484575, ENST00000862219, ENST00000862220, ENST00000862221, ENST00000862222, ENST00000862223, ENST00000862224, ENST00000862225, ENST00000862226, ENST00000862227, ENST00000862228, ENST00000862229, ENST00000862230, ENST00000911595, ENST00000911596, ENST00000911597, ENST00000911598, ENST00000911599, ENST00000911600, ENST00000911601, ENST00000911602, ENST00000911603, ENST00000911604, ENST00000911605, ENST00000961866, ENST00000961867

RefSeq mRNA: 3 — MANE Select: NM_005896 NM_001282386, NM_001282387, NM_005896

CCDS: CCDS2381

Canonical transcript exons

ENST00000345146 — 10 exons

Exon	Start	End
ENSE00000934681	208236229	208237169
ENSE00000934683	208239863	208240003
ENSE00000934684	208241994	208242145
ENSE00000934687	208248369	208248660
ENSE00001357891	208253886	208253959
ENSE00001908890	208254939	208255071
ENSE00002416886	208245319	208245424
ENSE00002424476	208243427	208243604
ENSE00003511233	208239071	208239233
ENSE00003564564	208251430	208251567

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.8896 / max 769.1031, expressed in 1809 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33449	49.7209	1804
33451	2.0021	1118
33446	1.9192	600
33450	0.5512	311
33448	0.5052	267
33442	0.4106	140
33447	0.2913	158
33444	0.1996	81
33445	0.1920	78
33443	0.0974	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.62	gold quality
jejunal mucosa	UBERON:0000399	99.50	gold quality
adrenal tissue	UBERON:0018303	99.47	gold quality
right adrenal gland cortex	UBERON:0035827	99.33	gold quality
right adrenal gland	UBERON:0001233	99.24	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.12	gold quality
colonic mucosa	UBERON:0000317	99.07	gold quality
left adrenal gland	UBERON:0001234	99.04	gold quality
adrenal cortex	UBERON:0001235	99.03	gold quality
left adrenal gland cortex	UBERON:0035825	98.94	gold quality
secondary oocyte	CL:0000655	98.92	gold quality
duodenum	UBERON:0002114	98.87	gold quality
oocyte	CL:0000023	98.74	gold quality
adrenal gland	UBERON:0002369	98.72	gold quality
seminal vesicle	UBERON:0000998	98.55	gold quality
caput epididymis	UBERON:0004358	98.55	gold quality
mucosa of transverse colon	UBERON:0004991	98.47	gold quality
rectum	UBERON:0001052	98.46	gold quality
cortical plate	UBERON:0005343	98.40	gold quality
pigmented layer of retina	UBERON:0001782	98.35	gold quality
liver	UBERON:0002107	98.32	gold quality
cauda epididymis	UBERON:0004360	98.32	gold quality
esophagus squamous epithelium	UBERON:0006920	98.26	gold quality
ganglionic eminence	UBERON:0004023	98.25	gold quality
embryo	UBERON:0000922	98.09	gold quality
germinal epithelium of ovary	UBERON:0001304	98.07	gold quality
mammary duct	UBERON:0001765	98.05	gold quality
adult organism	UBERON:0007023	98.03	gold quality
mammalian vulva	UBERON:0000997	97.96	gold quality
oral cavity	UBERON:0000167	97.92	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	119.52
E-MTAB-6678	yes	11.21
E-MTAB-3929	no	1189.55
E-MTAB-7037	no	108.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, FOXO3, FOXO4, FOXO6, SREBF1, SREBF2

miRNA regulators (miRDB)

72 targeting IDH1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 40)

• IDH1 activity is coordinately regulated with the cholesterol and fatty acid biosynthetic pathways and suggest that it is the source for the cytosolic NADPH required by these pathways (PMID:12923220)
• loss of IDPc and Prx-II during tumor development may involve in tumor progression and metastasis (PMID:15936593)
• genomic analysis of glioblastoma multiforme; recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) were found in 12% of the glioblastoma multiforme patients (PMID:18772396)
• Data show that the very high frequency of IDH1 mutations occurrs in diffuse astrocytomas, oligodendrogliomas, oligoastrocytomas and secondary glioblastomas. (PMID:18985363)
• These data indicate that cancer mutations affecting IDH1(R132) are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas. (PMID:19117336)
• Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas. (PMID:19228619)
• presence of IDH1 mutations in secondary glioblastomas and their near-complete absence in primary glioblastomas reinforce the concept that despite their histological similarities, these subtypes are genetically and clinically distinct entities (PMID:19246647)
• in families with Li-Fraumeni syndrome, study identified IDH1 mutations in 5 astrocytomas that developed in carriers of a TP53 germline mutation; all were R132C (CGT–>TGT) (PMID:19340432)
• Mutations of IDH1 is not detected in brain metastases of colorectal cancer. (PMID:19350208)
• IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway (PMID:19359588)
• study suggests that despite the infrequent incidence of the IDH1 mutations in prostate cancers and B-ALL, mutated IDH1 could be therapeutically targeted in these cancers and in glial tumors with the IDH1 mutations (PMID:19378339)
• Frequent IDH1 mutations in supratentorial primitive neuroectodermal tumors of adults. (PMID:19411854)
• IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. (PMID:19435942)
• Pilocytic astrocytomas had BRAF fusions in 70% of cases but not IDH1 or IDH2 mutations. Diffuse astrocytomas had IDH1 mutations in 76% of cases but not IDH2 mutations or BRAF fusions. Analysis of BRAF and IDH1 separates pilocytic from diffuse astrocytoma. (PMID:19543740)
• In patients with glioma, IDH1 mutations of the R132C type are strongly associated with astrocytoma. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations. (PMID:19554337)
• Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. (PMID:19636000)
• Mutation in IDH1 gene was found in acute myeloid leukemia. (PMID:19657110)
• Studies indicate that mutations in IDH1/IDH2 are specific for diffuse gliomas. (PMID:19667985)
• IDH1 mutations are a strong predictor of a more favorable prognosis and a highly selective molecular marker of secondary glioblastomas that complements clinical criteria for distinguishing them from primary glioblastomas. (PMID:19755387)
• IDH1 or IDH2 mutation plays a role in early tumor progression of several types of glioma (PMID:19765000)
• in glioblastoma patients managed according to current standards of care. MGMT promoter methylation and IDH1 mutational status allow for stratification into prognostically distinct subgroups. (PMID:19805672)
• Immunohistochemistry of primary brain tumors demonstrated a strong cytoplasmic and weaker nuclear staining OF IDH1 (PMID:19903171)
• 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)
• These results indicate that IDH1 mutations identify a subgroup of gliomas with an improved survival, but are unrelated to the temozolomide response. (PMID:19933982)
• data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas (PMID:19935646)
• analysis of non-p.R132H mutations in IDH1 in distinct molecular subtypes of glioma (PMID:20077503)
• Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation. (PMID:20097881)
• The prognostic IDH1( R132 ) mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma. (PMID:20127344)
• Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively of glioblastoma multiforme (PMID:20129251)
• Mutation of IDH1 appears to be a very strong prognostic factor in diffuse gliomas. (PMID:20133500)
• IDH1 mutation confer an enzymatic gain of function that dramatically increases 2-hydroxyglutarate in acute myelogenous leukemia (PMID:20142433)
• this homogeneously treated group of anaplastic oligodendroglioma patients, the presence of IDH1 mutations was found to carry a very strong prognostic significance for overall survival (PMID:20160062)
• Less than half of patients with cytogenetically normal acute myeloid leukemia with elevated 2-hydroxyglutarate possessed IDH1 mutations. (PMID:20171147)
• functionally relevant IDH1 mutations can also occur in thyroid cancer, particularly anaplastic thyroid cancer, suggesting a potential tumorigenic role of the IDH1 system that could represent a new therapeutic target for thyroid cancer. (PMID:20171178)
• IDH1 mutations are not associated with high-grade gliomas. (PMID:20174854)
• Isocitrate dehydrogenase 1 mutation R132H is associated with myelodysplastic syndrome. (PMID:20227112)
• Mutations in IDH seem to play an important role in the formation of specific subtypes of gliomas. (PMID:20367200)
• IDH1 SNP rs11554137 but not IDH1 R132 mutations are associated with an inferior outcome in cytogenetically normal acute myeloid leukemia. (PMID:20368538)
• IDH1 and IDH2 mutations are recurrent in de novo cytogenetically normal acute myeloid leukemia and have an unfavorable impact on outcome. (PMID:20368543)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	idh1	ENSDARG00000025375
mus_musculus	Idh1	ENSMUSG00000025950
rattus_norvegicus	Idh1	ENSRNOG00000015020
drosophila_melanogaster	Idh	FBGN0001248
caenorhabditis_elegans		WBGENE00010317

Paralogs (1): IDH2 (ENSG00000182054)

Protein

Protein identifiers

Isocitrate dehydrogenase [NADP] cytoplasmic — O75874 (reviewed: O75874)

Alternative names: Cytosolic NADP-isocitrate dehydrogenase, IDPc, NADP(+)-specific ICDH, Oxalosuccinate decarboxylase

All UniProt accessions (5): O75874, A0A024R3Y6, C9J4N6, C9JJE5, C9JLU6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase. Plays a critical role in the generation of NADPH, an important cofactor in many biosynthesis pathways. May act as a corneal epithelial crystallin and may be involved in maintaining corneal epithelial transparency.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol. Peroxisome.

Post-translational modifications. Acetylation at Lys-374 dramatically reduces catalytic activity.

Disease relevance. 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. Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors. Genetic variations are associated with cartilaginous tumors such as enchondroma or chondrosarcoma. Mutations of Arg-132 to Cys, Gly or His abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate.

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

Similarity. Belongs to the isocitrate and isopropylmalate dehydrogenases family.

RefSeq proteins (3): NP_001269315, NP_001269316, NP_005887* (*=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 (82 total): strand 19, helix 19, binding site 13, modified residue 10, sequence conflict 8, sequence variant 6, turn 3, site 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

61 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6BKX	X-RAY DIFFRACTION	1.65
4UMX	X-RAY DIFFRACTION	1.88
8VHB	X-RAY DIFFRACTION	1.89
6BL2	X-RAY DIFFRACTION	1.92
5GIR	X-RAY DIFFRACTION	1.93
6BKZ	X-RAY DIFFRACTION	2.01
6BL1	X-RAY DIFFRACTION	2.02
8T7O	X-RAY DIFFRACTION	2.05
4UMY	X-RAY DIFFRACTION	2.07
3INM	X-RAY DIFFRACTION	2.1
4L03	X-RAY DIFFRACTION	2.1
6VEI	X-RAY DIFFRACTION	2.1
7PJM	X-RAY DIFFRACTION	2.1
6U4J	X-RAY DIFFRACTION	2.11
8VH9	X-RAY DIFFRACTION	2.13
8VHE	X-RAY DIFFRACTION	2.16
6BKY	X-RAY DIFFRACTION	2.17
6BL0	X-RAY DIFFRACTION	2.17
6PAY	X-RAY DIFFRACTION	2.2
5TQH	X-RAY DIFFRACTION	2.2
6IO0	X-RAY DIFFRACTION	2.2
4KZO	X-RAY DIFFRACTION	2.2
5DE1	X-RAY DIFFRACTION	2.25
8T7N	X-RAY DIFFRACTION	2.26
8VHA	X-RAY DIFFRACTION	2.28
4L06	X-RAY DIFFRACTION	2.28
6B0Z	X-RAY DIFFRACTION	2.33
5SVF	X-RAY DIFFRACTION	2.34
8BAY	X-RAY DIFFRACTION	2.35
8VHD	X-RAY DIFFRACTION	2.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75874-F1	96.00	0.95

Antibody-complex structures (SAbDab): 1 — 5GIR

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): 139 (critical for catalysis); 212 (critical for catalysis)

Ligand- & substrate-binding residues (13): 260; 275 (in other chain); 279 (in other chain); 310–315; 328; 75–77; 77 (in other chain); 82; 94–100 (in other chain); 109 (in other chain); 132 (in other chain); 212 …

Post-translational modifications (10): 2, 42, 81, 126, 224, 233, 243, 321, 389, 400

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2978092	Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate
R-HSA-389542	NADPH regeneration
R-HSA-6798695	Neutrophil degranulation
R-HSA-9033241	Peroxisomal protein import
R-HSA-9818025	NFE2L2 regulating TCA cycle genes

MSigDB gene sets: 622 (showing top): RNGTGGGC_UNKNOWN, MODULE_93, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_NADPPLUS_METABOLIC_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS

GO Biological Process (12): 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), NADPH regeneration (GO:0006740), glutathione metabolic process (GO:0006749), response to oxidative stress (GO:0006979), female gonad development (GO:0008585), response to steroid hormone (GO:0048545), regulation of phospholipid catabolic process (GO:0060696), regulation of phospholipid biosynthetic process (GO:0071071)

GO Molecular Function (11): magnesium ion binding (GO:0000287), isocitrate dehydrogenase (NADP+) activity (GO:0004450), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), NADP binding (GO:0050661), NAD binding (GO:0051287), protein binding (GO:0005515), 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 (10): extracellular region (GO:0005576), cytoplasm (GO:0005737), mitochondrion (GO:0005739), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Diseases of metabolism	1
Metabolism of cofactors	1
Innate Immune System	1
Protein localization	1
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of phospholipid metabolic process	2
adenyl nucleotide binding	2
cytoplasm	2
intracellular organelle lumen	2
carbohydrate metabolic process	1
glyoxylate metabolic process	1
aerobic respiration	1
primary metabolic process	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
generation of precursor metabolites and energy	1
NADP+ metabolic process	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
response to stress	1
gonad development	1
development of primary female sexual characteristics	1
response to hormone	1
response to lipid	1
phospholipid catabolic process	1
regulation of lipid catabolic process	1
phospholipid biosynthetic process	1
regulation of lipid biosynthetic process	1
metal ion binding	1
isocitrate dehydrogenase [NAD(P)+] activity	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
cell adhesion molecule binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
cation binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
microbody	1

Protein interactions and networks

STRING

5207 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IDH1	FH	P07954	939
IDH1	CS	O75390	934
IDH1	MDH2	P40926	933
IDH1	MGMT	P16455	930
IDH1	IDH3G	P51553	924
IDH1	ACO1	P21399	918
IDH1	TET2	Q6N021	915
IDH1	ACO2	Q99798	914
IDH1	ASXL1	Q8IXJ9	899
IDH1	D2HGDH	Q8N465	895
IDH1	ATRX	P46100	887
IDH1	PTEN	P60484	836
IDH1	TP53	P04637	828
IDH1	ACLY	P53396	820
IDH1	FLT3	P36888	815

IntAct

110 interactions, top by confidence:

A	B	Type	Score
IDH1	IDH1	psi-mi:“MI:0407”(direct interaction)	0.760
IDH1	IDH1	psi-mi:“MI:0915”(physical association)	0.760
CALM1	IDH1	psi-mi:“MI:0407”(direct interaction)	0.650
IDH1	CALM1	psi-mi:“MI:0407”(direct interaction)	0.650
IDH1	CALM1	psi-mi:“MI:0915”(physical association)	0.650
	IDH1	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.620
CALR	IDH1	psi-mi:“MI:0915”(physical association)	0.560
SERPINH1	IDH1	psi-mi:“MI:0915”(physical association)	0.560
DLST	IDH1	psi-mi:“MI:0915”(physical association)	0.560
IDH1	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
IDH1	PRKACA	psi-mi:“MI:0915”(physical association)	0.560
	IDH1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (147): IDH1 (Affinity Capture-RNA), IDH1 (Affinity Capture-RNA), CAB39 (Co-fractionation), DAZAP1 (Co-fractionation), FAM49B (Co-fractionation), HSD17B4 (Co-fractionation), IDH1 (Co-fractionation), IDH1 (Co-fractionation), IDH1 (Co-fractionation), IDH1 (Co-fractionation), IDH1 (Co-fractionation), IDH1 (Co-fractionation), IDH1 (Co-fractionation), LTA4H (Co-fractionation), PCBP1 (Co-fractionation)

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

20 interactions.

A	Effect	B	Mechanism
SREBF1	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
SREBF2	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
IDH1	“up-regulates quantity”	2-oxoglutarate(2-)	“chemical modification”
IDH1	“down-regulates quantity”	D-threo-isocitrate(3-)
FOXO	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
FOXO3	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
FOXO1	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
FOXO4	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
FOXO6	“up-regulates quantity by expression”	IDH1	“transcriptional regulation”
D-threo-isocitrate(3-)	“up-regulates activity”	IDH1	“chemical activation”
CyclinA2/CDK2	“down-regulates quantity by destabilization”	IDH1	phosphorylation
SCF-SKP2	“down-regulates quantity by destabilization”	IDH1	ubiquitination
SKP2	“down-regulates quantity by destabilization”	IDH1	ubiquitination
FLT3	“up-regulates activity”	IDH1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAF activation	5	33.6×	8e-05
Oncogenic MAPK signaling	6	29.8×	3e-05
Signaling by BRAF and RAF1 fusions	5	17.0×	1e-03
Apoptosis	5	16.8×	1e-03
Programmed Cell Death	5	14.6×	2e-03
MAPK1/MAPK3 signaling	5	13.1×	2e-03
MAPK family signaling cascades	6	12.3×	1e-03
Diseases of signal transduction by growth factor receptors and second messengers	9	10.2×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of gene expression	9	5.4×	6e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

IDH1 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. The implications of mutations in this gene vary greatly by cancer type. In myelodysplastic syndromes and acute myeloid leukemia (AML), IDH1 mutations have been associated with worse outcome, shorter overall survival, and normal karyotype. However, in glioblastoma and astrocytoma, patients with IDH1 mutations have shown better overall survival than patients with wild-type IDH1. Unlike the association with cytogenetically normal AML, in glioblastoma, IDH1 mutations have been associated with specific cytogenetic abnormalities, 1p and 19q deletions.

From intOGen — cancer-driver classification: activating (oncogene-like) across 15 cancer types — AML, CHOL, GB, GBM, HCC, HGGNOS, LGGNOS, MBL, MEL, MT, OS, PAST…(+3 more).

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	277
Likely benign	163
Benign	21

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
375889	NM_005896.4(IDH1):c.395G>T (p.Arg132Leu)	Pathogenic
375893	NM_005896.4(IDH1):c.394C>A (p.Arg132Ser)	Pathogenic
1172783	NM_005896.4(IDH1):c.890G>T (p.Cys297Phe)	Likely pathogenic
134518	NM_005896.4(IDH1):c.565A>G (p.Ile189Val)	Likely pathogenic

SpliceAI

1517 predictions. Top by Δscore:

Variant	Effect	Δscore
2:208237166:CACA:C	acceptor_gain	1.0000
2:208237168:CA:C	acceptor_gain	1.0000
2:208237170:C:CC	acceptor_gain	1.0000
2:208237175:G:T	acceptor_gain	1.0000
2:208239068:TA:T	donor_loss	1.0000
2:208239069:A:AC	donor_gain	1.0000
2:208239069:ACTT:A	donor_loss	1.0000
2:208239070:C:CT	donor_gain	1.0000
2:208239229:GGAAG:G	acceptor_gain	1.0000
2:208239230:GAAG:G	acceptor_gain	1.0000
2:208239232:AG:A	acceptor_gain	1.0000
2:208239233:GCTA:G	acceptor_loss	1.0000
2:208239234:C:A	acceptor_loss	1.0000
2:208239234:C:CC	acceptor_gain	1.0000
2:208239235:T:G	acceptor_loss	1.0000
2:208239857:TCTTA:T	donor_loss	1.0000
2:208239858:CTTA:C	donor_loss	1.0000
2:208239860:TA:T	donor_loss	1.0000
2:208239861:A:AC	donor_gain	1.0000
2:208239862:C:CC	donor_gain	1.0000
2:208239862:CCA:C	donor_gain	1.0000
2:208239862:CCAA:C	donor_gain	1.0000
2:208240002:CC:C	acceptor_gain	1.0000
2:208240003:CC:C	acceptor_gain	1.0000
2:208242018:CG:C	donor_gain	1.0000
2:208242056:C:A	donor_gain	1.0000
2:208242142:CTGC:C	acceptor_gain	1.0000
2:208242146:C:CG	acceptor_loss	1.0000
2:208242147:T:A	acceptor_loss	1.0000
2:208243425:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000115308 (2:208253918 T>C), RS1000183975 (2:208250664 C>G,T), RS1000250959 (2:208247377 A>G), RS1000257393 (2:208250159 A>C,G), RS1000549437 (2:208253677 C>G), RS1000596516 (2:208249035 G>C), RS1000639377 (2:208239641 T>C), RS1000654976 (2:208236335 A>G), RS1000685832 (2:208236030 T>C), RS1000796527 (2:208243033 G>C), RS1000842769 (2:208256287 G>A), RS1001166504 (2:208243306 G>T), RS1001207377 (2:208241561 C>T), RS1001445910 (2:208248064 T>C), RS1001479841 (2:208247679 A>C)

Disease associations

OMIM: gene MIM:147700 | disease phenotypes: MIM:167400, MIM:166000, MIM:614875, MIM:137800, MIM:614569, MIM:601626

GenCC curated gene-disease

Disease	Classification	Inheritance
Maffucci syndrome	Limited	Autosomal dominant

Mondo (9): paroxysmal extreme pain disorder (MONDO:0008179), Ollier disease (MONDO:0008145), metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MONDO:0013941), glioma susceptibility 1 (MONDO:0024498), diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (MONDO:0858939), diffuse midline glioma, H3 K27-altered (MONDO:1060171), Maffucci syndrome (MONDO:0013808), acute myeloid leukemia (MONDO:0018874), lymphoma (MONDO:0005062)

Orphanet (6): Paroxysmal extreme pain disorder (Orphanet:46348), Ollier disease (Orphanet:296), Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (Orphanet:99646), Maffucci syndrome (Orphanet:163634), Acute myeloid leukemia (Orphanet:519), Lymphoma (Orphanet:223735)

HPO phenotypes

111 total (30 of 111 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000122	Unilateral renal agenesis
HP:0000233	Thin vermilion border
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000324	Facial asymmetry
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000400	Macrotia
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000519	Developmental cataract
HP:0000666	Horizontal nystagmus
HP:0000853	Goiter
HP:0000914	Shield chest
HP:0000926	Platyspondyly
HP:0000944	Abnormal metaphysis morphology
HP:0000958	Dry skin
HP:0001028	Hemangioma
HP:0001048	Cavernous hemangioma
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001367	Abnormal joint morphology
HP:0001387	Joint stiffness
HP:0001442	Typified by somatic mosaicism
HP:0001482	Subcutaneous nodule
HP:0001508	Failure to thrive
HP:0001510	Growth delay

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004347_2	Glioma	3.000000e-06
GCST004348_15	Non-glioblastoma glioma	2.000000e-10
GCST006904_9	Cerebral amyloid deposition (PET imaging)	5.000000e-06
GCST011004_8	Adult diffuse glioma (IDH mutation)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D008223	Lymphoma	C04.557.386; C15.604.515.569; C20.683.515.761
C563475	Paroxysmal Extreme Pain Disorder (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2007625 (SINGLE PROTEIN), CHEMBL4523659 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 14,723 (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
CHEMBL3989958	IVOSIDENIB	4	2,231
CHEMBL4279047	VORASIDENIB	4	504
CHEMBL4297610	OLUTASIDENIB	4	235
CHEMBL167779	ZUCLOMIPHENE	2	8,853
CHEMBL4167360	IDH305	2	442
CHEMBL4650282	DS-1001B	2	15
CHEMBL4651002	SAFUSIDENIB	2	16
CHEMBL6000618	CRELOSIDENIB	2	48
CHEMBL4206033	BAY1436032	1	64

Clinical evidence (CIViC)

Drug × variant × indication: 25 predictive associations from 27 curated evidence items; also 11 prognostic, 5 diagnostic, 1 predisposing.

Variant	Therapy	Indication	Effect	Level	CIViC
IDH1 Mutation	Ivosidenib + Azacitidine	Acute Myeloid Leukemia	Sensitivity/Response	CIViC A	EID10313
IDH1 Mutation	Ivosidenib	Acute Myeloid Leukemia	Sensitivity/Response	CIViC A	EID7278
IDH1 R132	Ivosidenib	Cholangiocarcinoma	Sensitivity/Response	CIViC A	EID10886
IDH1 R132	Ivosidenib	Chondrosarcoma	Sensitivity/Response	CIViC A	EID11194
IDH1 R132C OR IDH1 R132H OR IDH1 R132L OR IDH1 R132G OR IDH1 R132S	Vorasidenib	Low Grade Glioma	Sensitivity/Response	CIViC A	EID11508
IDH2 Mutation OR IDH1 Mutation	Vorasidenib	Glioma	Sensitivity/Response	CIViC A	EID11708
IDH1 R132	Cetuximab	Glioblastoma	Sensitivity/Response	CIViC B	EID3718 +1
IDH1 R132H	Temozolomide	Brain Glioma	Sensitivity/Response	CIViC B	EID2019 +1
IDH1 Mutation	Ivosidenib	Cholangiocarcinoma	Sensitivity/Response	CIViC B	EID7447
IDH1 R132	Bevacizumab + Sunitinib	High Grade Glioma	Sensitivity/Response	CIViC B	EID2020
IDH1 R132	Bevacizumab	High Grade Glioma	Sensitivity/Response	CIViC B	EID2330
IDH1 R132	Safusidenib	Glioma	Sensitivity/Response	CIViC B	EID7448
IDH1 R132C	Temozolomide	Brain Glioma	Sensitivity/Response	CIViC B	EID2327
IDH1 R132C	Ivosidenib	Acute Myeloid Leukemia	Sensitivity/Response	CIViC B	EID2331
IDH1 Mutation	Venetoclax	Acute Myeloid Leukemia	Sensitivity/Response	CIViC C	EID8856
IDH1 R132H	Ivosidenib	Pancreatic Ductal Adenocarcinoma	Sensitivity/Response	CIViC C	EID5987
IDH1 Mutation	Olaparib	Brain Glioma	Sensitivity/Response	CIViC D	EID2933
IDH1 R132	Dasatinib	Intrahepatic Cholangiocarcinoma	Sensitivity/Response	CIViC D	EID6439
IDH1 R132C	Olaparib	Cancer	Sensitivity/Response	CIViC D	EID10144
IDH1 R132C	AGI-5198	High Grade Glioma	Sensitivity/Response	CIViC D	EID2329
IDH1 R132C	BPTES	Acute Myeloid Leukemia	Sensitivity/Response	CIViC D	EID2332
IDH1 R132C	GSK321	Acute Myeloid Leukemia	Sensitivity/Response	CIViC D	EID732
IDH1 R132H	BPTES	Brain Glioma	Sensitivity/Response	CIViC D	EID2324
IDH1 R132H	Pan-Mutant-IDH1 Inhibitor Bay-1436032	Glioblastoma	Sensitivity/Response	CIViC D	EID2325
IDH1 R132H	AGI-5198	Oligodendroglioma	Sensitivity/Response	CIViC D	EID979

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs121913500	IDH1		0.00	0
rs121913499	IDH1		0.00	0

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 (4 total), top 4:

Ligand	Action	Affinity	Parameter
olutasidenib	Inhibition	7.0	pIC50
LY3410738	Inhibition	6.98	pIC50
safusidenib	Inhibition	6.89	pIC50
AGI-5198	Inhibition	4.89	pKi

Binding affinities (BindingDB)

2938 measured of 3714 human assays (3714 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(4R)-3-[2-[[(1S)-1-[1-[4-(difluoromethyl)phenyl]imidazol-4-yl]ethyl]amino]pyrimidin-4-yl]-4-[(1S)-1-fluoroethyl]-1,3-oxazolidin-2-one	IC50	1 nM	US-9688672: 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH
(4R)-3-[6-chloro-2-[[(1S)-1-[1-(4-chlorophenyl)imidazol-4-yl]ethyl]amino]pyrimidin-4-yl]-4-[(1R)-1-hydroxyethyl]-1,3-oxazolidin-2-one	IC50	3 nM	US-9688672: 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH
3-[6-chloro-2-[[(1S)-1-[1-(4-chlorophenyl)imidazol-4-yl]ethyl]amino]pyrimidin-4-yl]-4-[(1R)-1-hydroxyethyl]-1,3-oxazolidin-2-one	IC50	3 nM	US-9434719: 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH
2-methyl-2-[6-(6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-carbonyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-8-yl]propanenitrile	IC50	3 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
2-[6-(2,3-dihydro-1H-indene-2-carbonyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-8-yl]-2-methylpropanenitrile	IC50	3 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(1,3-dihydroisoindole-2-carbonyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	3 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(2,3-dimethylimidazol-4-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	3 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(1,2-oxazol-4-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	3 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-[2-(3-hydroxypyrrolidin-1-yl)-4-pyridinyl]-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	3 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
4-methyl-5-[6-(6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-carbonyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-8-yl]-1,3-oxazolidin-2-one	IC50	3 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
(4R)-4-propan-2-yl-3-[6-(6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-carbonyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-8-yl]-1,3-oxazolidin-2-one	IC50	3 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
6-methoxy-2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid	IC50	3 nM	US-9951027: Benzimidazol-2-amines as MIDH1 inhibitors
US10399972, Example 50	IC50	3.5 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
US10399972, Example 51	IC50	3.6 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
GSK321	IC50	3.8 nM
N-[6-[(3R,6R)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2H-1,4-oxazin-3-yl]-5-fluoro-2-pyridinyl]-5-cyano-3-methylpyridine-2-carboxamide	IC50	4 nM	US-10035794: Heterocyclic derivatives and their use in the treatment of neurological disorders
(4R)-3-[6-chloro-2-[[(1S)-1-[2-(4-chlorophenyl)-1,3-thiazol-5-yl]ethyl]amino]pyrimidin-4-yl]-4-[(1R)-1-hydroxyethyl]-1,3-oxazolidin-2-one	IC50	4 nM	US-9688672: 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH
(8-bromo-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl)-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	4 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
4-[10-(6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-carbonyl)-2,4,10,12-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-13-yl]pyrrolidin-2-one	IC50	4 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
3-[6-(6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-carbonyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-8-yl]-1,3-oxazolidin-2-one	IC50	4 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
2-(4-propan-2-ylanilino)-1-[(1S,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid	IC50	4 nM	US-9951027: Benzimidazol-2-amines as MIDH1 inhibitors
6-methyl-2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid	IC50	4 nM	US-9951027: Benzimidazol-2-amines as MIDH1 inhibitors
(+-) 6-methoxy-2-{[4-(trifluoromethoxy)phenyl]amino}-1-[(cis)-3,3,5-trimethylcyclohexyl]-1H-benzimidazole-5-carboxylic acid	IC50	4 nM	US-9951027: Benzimidazol-2-amines as MIDH1 inhibitors
1-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]-2-{[4-(trifluoromethoxy)phenyl]-amino}-1H-benzimidazole-5-carboxylic acid	IC50	4 nM	US-10370339: N-Methylbenzimidazoles as mIDH1 inhibitors
US10399972, Example 22	IC50	4.2 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
US10399972, Example 21	IC50	4.5 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
N-[6-[(3R,6R)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2H-1,4-oxazin-3-yl]-2-pyridinyl]-5-cyano-3-methylpyridine-2-carboxamide	IC50	5 nM	US-10035794: Heterocyclic derivatives and their use in the treatment of neurological disorders
(4R)-3-[2-[[(1S)-1-[1-[4-chloro-3-(trifluoromethoxy)phenyl]piperidin-4-yl]ethyl]amino]-5-fluoropyrimidin-4-yl]-4-(1-hydroxyethyl)-1,3-oxazolidin-2-one	IC50	5 nM	US-9434719: 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH
4-[(1S)-1-hydroxyethyl]-3-[2-[1-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)-4-pyridinyl]-1,3-thiazol-2-yl]ethylamino]pyrimidin-4-yl]-1,3-oxazolidin-2-one	IC50	5 nM	US-9434719: 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH
(8-morpholin-4-yl-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl)-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	5 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(1-methylpyrazol-4-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	5 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(2-methylpyrazol-3-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	5 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(5-ethoxy-3-pyridinyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	5 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-[2-(dimethylamino)-4-pyridinyl]-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	5 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(2-hydroxypropan-2-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	5 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-[(1S)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl]-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-[(1S,5R)-9-(2,2,2-trifluoroethyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl]methanone	IC50	5 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
(�) 3-(6-methyl-2-{[4-(trifluoromethoxy)phenyl]amino}-1-[(cis)-3,3,5-trimethylcyclohexyl]-1H-benzimidazol-5-yl)propanoic acid	IC50	5 nM	US-9957235: Benzimidazol-2-amines as mIDH1 inhibitors
US10399972, Example 24	IC50	5.6 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
US10399972, Example 54	IC50	5.6 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
US10399972, Example 52	IC50	5.7 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(2,4-dimethyl-1,3-thiazol-5-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	6 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-(6-methoxy-2-methyl-3-pyridinyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	IC50	6 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
[8-[(1R)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl]-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-[(1S,5R)-9-(2,2,2-trifluoroethyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl]methanone	IC50	6 nM	US-10086000: Tricyclic compounds as inhibitors of mutant IDH enzymes
6-methoxy-1-(3,3,5,5-tetramethylcyclohexyl)-2-[4-(trifluoromethoxy)anilino]benzimidazole-5-carboxylic acid	IC50	6 nM	US-9951027: Benzimidazol-2-amines as MIDH1 inhibitors
[6-chloro-2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carbonyl]-methylcarbamic acid	IC50	6 nM	US-9951027: Benzimidazol-2-amines as MIDH1 inhibitors
US10399972, Example 19	IC50	6 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
US10399972, Example 10	IC50	6.2 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes
1-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]-2-(4-propan-2-ylanilino)benzimidazole-5-carboxylic acid	IC50	6.3 nM	US-10370339: N-Methylbenzimidazoles as mIDH1 inhibitors
2-[6-methyl-1-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]-2-[4-(trifluoromethoxy)anilino]benzimidazol-5-yl]acetic acid	IC50	6.3 nM	US-10370339: N-Methylbenzimidazoles as mIDH1 inhibitors
US10399972, Example 55	IC50	6.5 nM	US-10399972: Tricyclic compounds as inhibitors of mutant IDH enzymes

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	IC50	0.04	nM	VORASIDENIB
9.60	IC50	0.25	nM	CHEMBL4278845
9.52	IC50	0.3	nM	CHEMBL4283785
9.46	IC50	0.349	nM	CHEMBL5633097
9.37	EC50	0.43	nM	CHEMBL4448475
9.36	IC50	0.44	nM	CHEMBL5633097
9.15	IC50	0.7	nM	CHEMBL4280132
9.00	IC50	1	nM	CHEMBL3909586
9.00	IC50	1	nM	CHEMBL4289465
9.00	IC50	1	nM	CHEMBL4278793
9.00	IC50	1	nM	CHEMBL4280772
9.00	IC50	1	nM	CHEMBL4277352
9.00	IC50	1	nM	CHEMBL4442678
9.00	IC50	1	nM	CHEMBL4444067
9.00	IC50	1	nM	OLUTASIDENIB
8.70	IC50	2	nM	CHEMBL4463644
8.70	IC50	2	nM	CHEMBL4439421
8.70	IC50	2	nM	CHEMBL4456610
8.70	IC50	2	nM	CHEMBL4278828
8.68	IC50	2.1	nM	CHEMBL4529476
8.67	IC50	2.12	nM	CHEMBL4548637
8.66	IC50	2.2	nM	CHEMBL4469477
8.64	IC50	2.3	nM	CHEMBL4467991
8.60	IC50	2.49	nM	CHEMBL5965796
8.57	IC50	2.7	nM	CHEMBL4475715
8.56	IC50	2.76	nM	CHEMBL5965796
8.54	IC50	2.9	nM	CHEMBL4215717
8.52	IC50	3	nM	CHEMBL3980822
8.52	IC50	3	nM	CHEMBL3979625
8.52	IC50	3	nM	CHEMBL4282663
8.52	IC50	3	nM	CHEMBL4289061
8.52	IC50	3	nM	CHEMBL4442678
8.52	IC50	3	nM	CHEMBL5632996
8.52	IC50	3	nM	CHEMBL5818979
8.52	IC50	3	nM	CHEMBL5857395
8.52	IC50	3	nM	CHEMBL5774790
8.52	IC50	3	nM	CHEMBL5784341
8.52	IC50	3	nM	CHEMBL5785951
8.52	IC50	3	nM	CHEMBL5948872
8.52	IC50	3	nM	CHEMBL5955195
8.52	IC50	3	nM	CHEMBL5787591
8.52	IC50	3	nM	CHEMBL5946895
8.52	IC50	3	nM	CHEMBL5805061
8.52	IC50	3	nM	BAY1436032
8.46	IC50	3.5	nM	CHEMBL4436236
8.46	IC50	3.5	nM	IVOSIDENIB
8.44	IC50	3.6	nM	CHEMBL5829285
8.43	IC50	3.71	nM	CRELOSIDENIB
8.42	IC50	3.8	nM	CHEMBL4215717
8.40	IC50	4	nM	CHEMBL3962229

PubChem BioAssay actives

1399 with measured affinity, of 2632 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
Vorasidenib	1513086: Inhibition of IDH1 R132C mutant (unknown origin) assessed as reduction in 2-HG levels after 90 mins in presence of NADPH by resazurin-based assay	ic50	<0.0001	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	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0003	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis(1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0003	uM
(E)-3-[1-[3-(2,6-dichlorophenyl)-5-(1-prop-2-enoylpiperidin-4-yl)-1,2-oxazole-4-carbonyl]indol-4-yl]prop-2-enoic acid	2135299: Inhibition of human wild type IDH1 R132H mutant expressed in Escherichia coli BL21 (DE3) cells incubated for 60 mins by fluorescence based analysis	ic50	0.0003	uM
1-(5-chloro-2-ethylphenyl)-3-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-6-(2-methylprop-1-enyl)-5-(piperazine-1-carbonyl)pyridin-2-one	1753747: Inhibition of IDH1 R132H mutant (unknown origin) expressed in human U87 cells assessed as R-2-hydroxyglutarate production after 48 hrs by LC-MS analysis	ec50	0.0004	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis(3,3-difluorocyclopentyl)-1,3,5-triazine-2,4-diamine	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0007	uM
2-N,4-N-bis(3,3-difluorocyclobutyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0010	uM
2-[[(1S)-1-(6-chloro-7-methoxy-2-oxo-1H-quinolin-3-yl)ethyl]amino]-4-methoxypyrimidine-5-carbonitrile	1562431: Inhibition of human Myc-DDK-tagged IDH1 R132H mutant expressed in human U87MG cells assessed as reduction in 2-HG levels after 24 hrs by RapidFire high-throughput mass spectrometry assay	ic50	0.0010	uM
(2S)-2-(2-chlorophenyl)-2-(N-[2-[(2S)-1-(4-cyano-2-pyridinyl)-5-oxopyrrolidin-2-yl]acetyl]-3,5-difluoroanilino)-N-(3,3-difluorocyclobutyl)acetamide	1410246: Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2-hydroxyglutarate production by LC-MS/MS analysis	ic50	0.0010	uM
(2S)-2-(2-chlorophenyl)-2-(N-[2-[(2S,4S)-1-(4-cyano-2-pyridinyl)-4-hydroxy-5-oxopyrrolidin-2-yl]acetyl]-3,5-difluoroanilino)-N-(3,3-difluorocyclobutyl)acetamide	1410246: Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2-hydroxyglutarate production by LC-MS/MS analysis	ic50	0.0010	uM
(4S)-4-propan-2-yl-3-[2-[[(1S)-1-[7-(trifluoromethyl)-4,5-dihydroimidazo[1,5-a]quinolin-3-yl]ethyl]amino]pyrimidin-4-yl]-1,3-oxazolidin-2-one	1610104: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	ic50	0.0010	uM
2-N,4-N-bis(3,3-difluorocyclopentyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0010	uM
2-N,4-N-bis[(1R)-1-cyclopropylethyl]-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0020	uM
5-[[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1H-quinolin-3-yl]ethyl]amino]-1-methyl-6-oxopyridine-2-carbonitrile	1529106: Inhibition of IDH1 R132H mutant in human HCT116 cells assessed as reduction in 2-HG levels after 24 hrs by RapidFire high-throughput mass spectrometry assay	ic50	0.0020	uM
5-[[(1S)-1-[6-chloro-7-(cyclopropylmethoxy)-2-oxo-1H-quinolin-3-yl]ethyl]amino]-1-methyl-6-oxopyridine-2-carbonitrile	1529106: Inhibition of IDH1 R132H mutant in human HCT116 cells assessed as reduction in 2-HG levels after 24 hrs by RapidFire high-throughput mass spectrometry assay	ic50	0.0020	uM
5-[[(1S)-1-[6-chloro-2-oxo-7-[(1R)-1-pyridin-2-ylethoxy]-1H-quinolin-3-yl]ethyl]amino]-1-methyl-6-oxopyridine-2-carbonitrile	1529106: Inhibition of IDH1 R132H mutant in human HCT116 cells assessed as reduction in 2-HG levels after 24 hrs by RapidFire high-throughput mass spectrometry assay	ic50	0.0020	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	1513096: Inhibition of IDH1 R132H mutant (unknown origin) using alpha-KG as substrate after 90 mins	ic50	0.0020	uM
(4S)-3-[2-[[(1S)-1-[5-(2-tert-butyl-4-pyridinyl)-2-pyridinyl]ethyl]amino]pyrimidin-4-yl]-4-propan-2-yl-1,3-oxazolidin-2-one	1504056: Inhibition of IDH1 R132H mutant in human HCT116 cells assessed as reduction in 2-HG level after 48 hrs by LC-MS/MS analysis	ic50	0.0020	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	1513096: Inhibition of IDH1 R132H mutant (unknown origin) using alpha-KG as substrate after 90 mins	ic50	0.0020	uM
(4R)-4-[(1S)-1-fluoroethyl]-3-[5-fluoro-2-[[(1S)-1-[7-(trifluoromethyl)-4,5-dihydroimidazo[1,5-a]quinolin-3-yl]ethyl]amino]pyrimidin-4-yl]-1,3-oxazolidin-2-one	1610104: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	ic50	0.0021	uM
(4R)-3-[6-chloro-2-[[(1S)-1-[7-(trifluoromethyl)-4,5-dihydroimidazo[1,5-a]quinolin-3-yl]ethyl]amino]pyrimidin-4-yl]-4-[(1S)-1-fluoroethyl]-1,3-oxazolidin-2-one	1610104: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	ic50	0.0021	uM
(4R)-3-[2-[[(1S)-1-(7-chloro-4H-imidazo[5,1-c][1,4]benzoxazin-3-yl)ethyl]amino]pyrimidin-4-yl]-4-[(1S)-1-fluoroethyl]-1,3-oxazolidin-2-one	1610104: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	ic50	0.0022	uM
(4R)-3-[2-[[(1S)-1-(7-chloro-4,5-dihydroimidazo[1,5-a]quinolin-3-yl)ethyl]amino]pyrimidin-4-yl]-4-[(1S)-1-fluoroethyl]-1,3-oxazolidin-2-one	1610104: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	ic50	0.0023	uM
(4R)-4-[(1S)-1-fluoroethyl]-3-[2-[[(1S)-1-[7-(trifluoromethyl)-4H-imidazo[5,1-c][1,4]benzoxazin-3-yl]ethyl]amino]pyrimidin-4-yl]-1,3-oxazolidin-2-one	1610104: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	ic50	0.0027	uM
(7R)-1-[(4-fluorophenyl)methyl]-N-[3-[(1S)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-6,7-dihydro-4H-pyrazolo[4,5-c]pyridine-3-carboxamide	1801986: RapidFire-MS/MS and NADPH Assays from Article 10.1038/nchembio.1930: “New IDH1 mutant inhibitors for treatment of acute myeloid leukemia”	ic50	0.0029	uM
2-methyl-2-[6-(6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-carbonyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-8-yl]propanenitrile	2135303: Inhibition of C-terminal His8-tagged human recombinant IDH1 R132H mutant expressed as Escherichia coli BL21 (DE3) cells using alpha KG as substrate preincubated with compound for 30 mins followed by substrate addition measured after 1.5 hrs by HTS assay	ic50	0.0030	uM
(2S)-2-(2-chlorophenyl)-2-(N-[2-[(2S)-1-(4-cyano-2-pyridinyl)-5-oxopyrrolidin-2-yl]acetyl]-3-fluoroanilino)-N-(3,3-difluorocyclobutyl)acetamide	1410246: Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2-hydroxyglutarate production by LC-MS/MS analysis	ic50	0.0030	uM
(2S)-2-(2-chlorophenyl)-2-[[2-[(2S)-1-(4-cyano-2-pyridinyl)-5-oxopyrrolidin-2-yl]acetyl]-(5-fluoro-3-pyridinyl)amino]-N-(3,3-difluorocyclobutyl)acetamide	1410261: Inhibition of IDH1 R132H mutant in human Neurospheres assessed as reduction in 2-hydroxyglutarate production by LC-MS/MS analysis	ic50	0.0030	uM
[3,9-difluoro-8-(2-methylpyrazol-3-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]methanone	1513063: Inhibition of IDH1 R132C mutant (unknown origin) by kinase-Glo luminescent assay	ic50	0.0035	uM
Ivosidenib	1610104: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	ic50	0.0035	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis(1-cyclopropylpropyl)-1,3,5-triazine-2,4-diamine	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0040	uM
2-[[(1S)-1-(6-chloro-2-oxo-7-propan-2-yloxy-1H-quinolin-3-yl)ethyl]amino]-4-methoxypyrimidine-5-carbonitrile	1562423: Inhibition of human Myc-DDK-tagged IDH1 R132H mutant assessed as reduction in NADPH consumption pre-incubated for 15 mins followed by alpha-ketoglutarate substrate and NADPH addition after 45 mins by diaphorase and resazurin dye based assay	ic50	0.0040	uM
5-[[(1S)-1-(6-chloro-7-methoxy-2-oxo-1H-quinolin-3-yl)ethyl]amino]-1-methyl-6-oxopyridine-2-carbonitrile	1529106: Inhibition of IDH1 R132H mutant in human HCT116 cells assessed as reduction in 2-HG levels after 24 hrs by RapidFire high-throughput mass spectrometry assay	ic50	0.0040	uM
(4R)-4-[(1S)-1-fluoroethyl]-3-[2-[[(1S)-1-[7-(trifluoromethyl)-4,5-dihydroimidazo[1,5-a]quinolin-3-yl]ethyl]amino]pyrimidin-4-yl]-1,3-oxazolidin-2-one	1610104: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition measured for 60 mins in presence of NADPH by diaphorase/resazurin-based assay	ic50	0.0040	uM
(4R)-3-[2-[[(1S)-1-[1-(4-chlorophenyl)imidazol-4-yl]ethyl]amino]pyrimidin-4-yl]-4-[(1S)-1-fluoroethyl]-1,3-oxazolidin-2-one	1385229: Inhibition of IDH1 R132H mutant (unknown origin) expressed in HCT116 cells assessed as reduction in 2-HG levels after 48 hrs by LC-MS/MS analysis	ic50	0.0040	uM
2-N,4-N-bis(4,4-difluorocyclohexyl)-6-[6-(trifluoromethyl)-2-pyridinyl]-1,3,5-triazine-2,4-diamine	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0040	uM
N-[1-[4-[(1S)-1-[[5-fluoro-4-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]pyrimidin-2-yl]amino]ethyl]phenyl]piperidin-4-yl]ethenesulfonamide	2018065: Inhibition of IDH1 R132H mutant (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as NADPH consumption using alpha-KG as substrate measured after 60 mins	ic50	0.0047	uM
[3-fluoro-8-(1-methylpyrazol-4-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-[(2R,5S)-5-propan-2-yloxyoxan-2-yl]methanone	1827810: Inhibition of IDH1 R132H mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-KG as substrate incubated for 60 mins by Kinase-GLO reagent based assay	ic50	0.0049	uM
(8-morpholin-4-yl-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl)-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	2124535: Inhibition of IDH1 R132H mutant (unknown origin) using alpha-ketoglutarate as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hrs by kinase-Glo detection reagent based luminescence reader	ic50	0.0050	uM
[8-(2-methylpyrazol-3-yl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone	2135303: Inhibition of C-terminal His8-tagged human recombinant IDH1 R132H mutant expressed as Escherichia coli BL21 (DE3) cells using alpha KG as substrate preincubated with compound for 30 mins followed by substrate addition measured after 1.5 hrs by HTS assay	ic50	0.0050	uM
3-[2-[[(1S)-1-[4-[2-cyclopropyl-1-(4-prop-2-enoylpiperazin-1-yl)ethyl]phenyl]ethyl]amino]-6-fluoropyrimidin-4-yl]-4,4-dimethyl-1,3-oxazolidin-2-one	2135257: Inhibition of IDH1 R132C mutant (unknown origin) expressed in Escherichia coli BL21 (DE3) cells	ic50	0.0050	uM
(2S)-1-(4-cyano-2-pyridinyl)-N-[(1S)-1-[(3,3-difluorocyclobutyl)carbamoyl]-2,3-dihydroinden-1-yl]-N-(3,5-difluorophenyl)-5-oxopyrrolidine-2-carboxamide	1366779: Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2-hydroxyglutarate production after 48 hrs by LC-MS/MS analysis	ic50	0.0050	uM
(4S)-N-[(1S)-7-chloro-1-[(3,3-difluorocyclobutyl)carbamoyl]-2,3-dihydroinden-1-yl]-3-(4-cyanopyrimidin-2-yl)-N-(3-fluorophenyl)-2-oxo-1,3-oxazolidine-4-carboxamide	1366778: Inhibition of IDH1 R132H mutant (unknown origin) using alpha-ketoglutarate as substrate after 60 mins by resazurin dye based fluorescence assay	ic50	0.0056	uM
N-[2-fluoro-4-[4-[(1S)-1-[[5-fluoro-4-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]pyrimidin-2-yl]amino]ethyl]anilino]phenyl]ethenesulfonamide	2018065: Inhibition of IDH1 R132H mutant (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as NADPH consumption using alpha-KG as substrate measured after 60 mins	ic50	0.0059	uM
(2-hydroxyspiro[3.3]heptan-6-yl)-(8-morpholin-4-yl-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl)methanone	2135303: Inhibition of C-terminal His8-tagged human recombinant IDH1 R132H mutant expressed as Escherichia coli BL21 (DE3) cells using alpha KG as substrate preincubated with compound for 30 mins followed by substrate addition measured after 1.5 hrs by HTS assay	ic50	0.0059	uM
Olutasidenib	1529110: Inhibition of human Myc-DDK-tagged IDH1 R132G mutant expressed in human U87MG cells assessed as reduction in 2-HG levels after 24 hrs by rapidfire high-throughput mass spectrometric assay	ic50	0.0060	uM
4-[[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1H-quinolin-3-yl]methylamino]-2-methoxybenzonitrile	1562423: Inhibition of human Myc-DDK-tagged IDH1 R132H mutant assessed as reduction in NADPH consumption pre-incubated for 15 mins followed by alpha-ketoglutarate substrate and NADPH addition after 45 mins by diaphorase and resazurin dye based assay	ic50	0.0060	uM
(E)-3-[1-[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazole-4-carbonyl]indol-4-yl]prop-2-enoic acid	2135299: Inhibition of human wild type IDH1 R132H mutant expressed in Escherichia coli BL21 (DE3) cells incubated for 60 mins by fluorescence based analysis	ic50	0.0060	uM
(E)-3-[1-[5-(2-methoxypropan-2-yl)-3-(2,4,6-trichlorophenyl)-1,2-oxazole-4-carbonyl]indol-4-yl]prop-2-enoic acid	2135299: Inhibition of human wild type IDH1 R132H mutant expressed in Escherichia coli BL21 (DE3) cells incubated for 60 mins by fluorescence based analysis	ic50	0.0060	uM
6-(6-chloro-2-pyridinyl)-2-N,4-N-bis(4,4-difluorocyclohexyl)-1,3,5-triazine-2,4-diamine	1541884: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis	ic50	0.0070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	6
bisphenol A	decreases expression, increases expression	3
Acetaminophen	decreases expression	3
Nickel	decreases expression	3
Tretinoin	affects reaction, increases expression, affects response to substance, affects cleavage, affects expression	3
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	affects expression, increases expression	3
deoxynivalenol	decreases expression	2
tris(1,3-dichloro-2-propyl)phosphate	affects expression, decreases expression, increases abundance	2
ochratoxin A	decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression	2
Copper	increases expression, affects binding	2
Estradiol	decreases expression, affects cotreatment, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Aflatoxin B1	decreases expression	2
aristolochic acid I	increases expression, decreases expression	1
FR900359	increases phosphorylation	1
p-carboxymethylphenyl 1,1-bis(3’-indolyl)-1-(p-carboxymethylphenyl)methane	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
methylmercuric chloride	increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	decreases expression, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1

ChEMBL screening assays

488 unique, capped per target: 475 binding, 12 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1963857	Functional	PUBCHEM_BIOASSAY: qHTS for Inhibitors of mutant isocitrate dehydrogenase 1 (IDH1): Cherrypicks in WT IDH1. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL2188252	Binding	Inhibition of wild type IDH1 using DL-isocitrate as substrate by resazurin-based fluorimetric analysis relative to control	Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo. — ACS Med Chem Lett
CHEMBL4135750	ADMET	Inhibition of wild-type IDH1 (unknown origin) assessed as NADPH production using isocitrate as substrate by fluorescence assay	Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor. — ACS Med Chem Lett

Cellosaurus cell lines

168 cell lines: 156 cancer cell line, 8 spontaneously immortalized cell line, 2 induced pluripotent stem cell, 2 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0020	U-138MG	Cancer cell line	Male
CVCL_0021	U-251MG	Cancer cell line	Male
CVCL_0022	U-87MG ATCC	Cancer cell line	Male
CVCL_0115	2fTGH	Cancer cell line	Male
CVCL_0131	A-172	Cancer cell line	Male
CVCL_0317	HT-1080	Cancer cell line	Male
CVCL_0556	T98G	Cancer cell line	Male
CVCL_0633	U-118MG	Cancer cell line	Male
CVCL_1118	CCF-STTG1	Cancer cell line	Female
CVCL_1138	COR-L105	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	PHASE4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	PHASE4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	PHASE4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	PHASE4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	PHASE4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	PHASE4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	PHASE4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT00000589	PHASE3	COMPLETED	Trial to Reduce Alloimmunization to Platelets (TRAP)
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00093990	PHASE3	COMPLETED	Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT00125606	PHASE3	TERMINATED	Phase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide
NCT00136084	PHASE3	COMPLETED	Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00146120	PHASE3	COMPLETED	Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
NCT00150878	PHASE3	TERMINATED	Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
NCT00151255	PHASE3	COMPLETED	All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00152594	PHASE3	TERMINATED	Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia
NCT00186966	PHASE3	COMPLETED	Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
NCT00226512	PHASE3	WITHDRAWN	To Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning
NCT00260832	PHASE3	COMPLETED	Trial of Decitabine in Patients With Acute Myeloid Leukemia