DHODH

Summary

DHODH (dihydroorotate dehydrogenase (quinone), HGNC:2867) is a protein-coding gene on chromosome 16q22.2, encoding Dihydroorotate dehydrogenase (quinone), mitochondrial (Q02127). Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. It is a selective cancer dependency (DepMap: 33.9% of cell lines).

The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis. This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane.

Source: NCBI Gene 1723 — RefSeq curated summary.

At a glance

• Gene–disease (curated): postaxial acrofacial dysostosis (Definitive, ClinGen)
• GWAS associations: 10
• Clinical variants (ClinVar): 206 total — 7 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 33.9% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2867
Approved symbol	DHODH
Name	dihydroorotate dehydrogenase (quinone)
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000102967
Ensembl biotype	protein_coding
OMIM	126064
Entrez	1723

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000219240, ENST00000571288, ENST00000571392, ENST00000572003, ENST00000572887, ENST00000573843, ENST00000573922, ENST00000574309, ENST00000576145, ENST00000894311, ENST00000894312, ENST00000894313, ENST00000936684, ENST00000936685, ENST00000936686, ENST00000958705

RefSeq mRNA: 1 — MANE Select: NM_001361 NM_001361

CCDS: CCDS42192

Canonical transcript exons

ENST00000219240 — 9 exons

Exon	Start	End
ENSE00001420633	72008744	72008785
ENSE00002294141	72023474	72023633
ENSE00002320279	72024145	72027659
ENSE00003655449	72014473	72014672
ENSE00003787913	72017024	72017106
ENSE00003888793	72021124	72021311
ENSE00003888872	72023165	72023318
ENSE00003893801	72022362	72022475
ENSE00003895245	72012050	72012262

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 96.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0777 / max 312.4279, expressed in 1621 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154941	5.5774	1619
154942	0.1417	10
154943	0.1166	9
154946	0.0856	8
154945	0.0824	10
154944	0.0739	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.51	gold quality
liver	UBERON:0002107	91.31	gold quality
right atrium auricular region	UBERON:0006631	89.05	gold quality
cardiac atrium	UBERON:0002081	85.93	gold quality
apex of heart	UBERON:0002098	82.85	gold quality
tibial nerve	UBERON:0001323	82.53	gold quality
muscle of leg	UBERON:0001383	81.89	gold quality
right ovary	UBERON:0002118	81.83	gold quality
gastrocnemius	UBERON:0001388	81.82	gold quality
left ovary	UBERON:0002119	81.54	gold quality
sural nerve	UBERON:0015488	81.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.36	gold quality
omental fat pad	UBERON:0010414	81.33	gold quality
peritoneum	UBERON:0002358	81.26	gold quality
left uterine tube	UBERON:0001303	80.78	gold quality
right uterine tube	UBERON:0001302	80.52	gold quality
right lobe of thyroid gland	UBERON:0001119	80.51	gold quality
ventricular zone	UBERON:0003053	80.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.01	gold quality
heart	UBERON:0000948	79.62	gold quality
rectum	UBERON:0001052	79.52	gold quality
cortical plate	UBERON:0005343	79.37	gold quality
body of uterus	UBERON:0009853	79.36	gold quality
left coronary artery	UBERON:0001626	79.34	gold quality
left lobe of thyroid gland	UBERON:0001120	79.32	gold quality
endocervix	UBERON:0000458	79.19	gold quality
right coronary artery	UBERON:0001625	79.07	gold quality
ganglionic eminence	UBERON:0004023	78.82	gold quality
heart left ventricle	UBERON:0002084	78.80	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, TBP

miRNA regulators (miRDB)

82 targeting DHODH, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 33.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 30)

• biophysical analysis of hydrogen bonding pathways in human dihydroorotate dehydrogenase (PMID:17004840)
• Data provide new insights into the dynamic features of the DHODH reaction and suggest new approaches to the design of inhibitors against DHODH. (PMID:18672895)
• DHODH polymorphism may be associated with incireased remiaaion in leflunomide treatment in rheumatoid arthritis patients. (PMID:19207032)
• we report a new association of DHODH A40C polymorphism with leflunomide toxicity in patients with Rheumatoid Arthritis. (PMID:19605743)
• Data confirmed the presence of DHODH mutations in families with Miller syndrome. (PMID:19915526)
• DHODH recessively causes Miller syndrome. (PMID:20220176)
• required for N-(4-hydroxyphenyl)retinamide-induced reactive oxygen species production and apoptosis of cancer epithelial cells (PMID:20399851)
• DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in xenograft studies (PMID:21430780)
• biallelic DHODH mutations in four unrelated families with typical clinical features of Miller syndrome. (PMID:22692683)
• Carriage of a six-marker DHODH haplotype was associated with a reduced treatment response (p = 0.008). (PMID:22966891)
• The G202A and R346W mutation causes deficient protein stability, and the R135C mutation impairs the substrate-induced enzymatic activity, suggesting that impairment of DHODH activity is linked to the Miller syndrome phenotype. (PMID:22967083)
• Considering that pyrimidine deficiency alone does not induce craniofacial dysmorphism, the DHODH mutations may contribute to the Miller syndrome in part through somehow altered mitochondrial function. (PMID:23216091)
• This is the first study to report on conformational changes of the HsDHODH N-terminal microdomain through a combination of CD and DEER spectroscopic techniques (PMID:26086954)
• This case with grossly raised plasma DHO represents the first biochemical confirmation of functional DHODH deficiency. DHO was also easily detectable in dried plasma and blood spots. (PMID:27370710)
• The authors show that DHODH-driven pyrimidine biosynthesis is an essential pathway linking respiration to tumorigenesis, pointing to inhibitors of DHODH as potential anti-cancer agents. (PMID:30449682)
• he preliminary structure-activity relationship was investigated. Compound 9 of biphenyl series and compound 37 of amide series displayed IC50 values of 1.32 muM and 1.45 muM, respectively. This research will provide valuable reference for the research of new structures of hDHODH inhibitors (PMID:31370178)
• These findings implicate DHODH and PCK1 in the colorectal cancer metastatic progression via pyrimidine nucleotide biosynthesis under hypoxia. (PMID:31841108)
• Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer. (PMID:32151633)
• Elevated DHODH expression promotes cell proliferation via stabilizing beta-catenin in esophageal squamous cell carcinoma. (PMID:33060568)
• SOX2-dependent expression of dihydroorotate dehydrogenase regulates oral squamous cell carcinoma cell proliferation. (PMID:33510132)
• DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. (PMID:33981038)
• DHODH tangoing with GPX4 on the ferroptotic stage. (PMID:34145214)
• Protein production, kinetic and biophysical characterization of three human dihydroorotate dehydrogenase mutants associated with Miller syndrome. (PMID:35094635)
• Protein-lipid interactions of human dihydroorotate dehydrogenase and three mutants associated with Miller syndrome. (PMID:35184687)
• New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition. (PMID:35269583)
• DHODH is an independent prognostic marker and potent therapeutic target in neuroblastoma. (PMID:35943801)
• Screening for DAX1/EWS-FLI1 functional inhibitors identified dihydroorotate dehydrogenase as a therapeutic target for Ewing’s sarcoma. (PMID:36825574)
• Exploiting Cancer Vulnerabilities by Blocking of the DHODH and GPX4 Pathways: A Multifunctional Bodipy/PROTAC Nanoplatform for the Efficient Synergistic Ferroptosis Therapy. (PMID:37204046)
• Pivotal role of dihydroorotate dehydrogenase as a therapeutic target in adult T-cell leukemia. (PMID:38558052)
• Bioinformatics analysis and experimental verification of the cancer-promoting effect of DHODH in clear cell renal cell carcinoma. (PMID:38796629)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhodh	ENSDARG00000051889
danio_rerio	dpyda.1	ENSDARG00000102671
mus_musculus	Dhodh	ENSMUSG00000031730
rattus_norvegicus	Dhodh	ENSRNOG00000015063
drosophila_melanogaster	Dhod	FBGN0000447
caenorhabditis_elegans	dhod-1	WBGENE00020932

Paralogs (2): FDXR (ENSG00000161513), DPYD (ENSG00000188641)

Protein

Protein identifiers

Dihydroorotate dehydrogenase (quinone), mitochondrial — Q02127 (reviewed: Q02127)

Alternative names: Dihydroorotate oxidase

All UniProt accessions (5): Q02127, I3L449, I3NI32, J3QRJ4, J3QRQ3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Required for UMP biosynthesis via de novo pathway.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion inner membrane.

Post-translational modifications. The uncleaved transit peptide is required for mitochondrial targeting and proper membrane integration.

Disease relevance. Postaxial acrofacial dysostosis (POADS) [MIM:263750] An autosomal recessive syndrome characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 FMN per subunit.

Pathway. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; orotate from (S)-dihydroorotate (quinone route): step 1/1.

Miscellaneous. The identification of DHODH defects as the cause of postaxial acrofacial dysostosis (POADS) was obtained via exome sequencing, demonstrating that this method is a powerful tool for identifying genes underlying rare Mendelian disorders. Exome sequencing consists of targeted resequencing of all protein-coding subsequences, which requires around 5% as much sequencing as a whole human genome.

Similarity. Belongs to the dihydroorotate dehydrogenase family. Type 2 subfamily.

RefSeq proteins (1): NP_001352* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001295	Dihydroorotate_DH_CS	Conserved_site
IPR005719	Dihydroorotate_DH_2	Family
IPR005720	Dihydroorotate_DH_cat	Domain
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR050074	DHO_dehydrogenase	Family

Pfam: PF01180

Enzyme classification (BRENDA):

• EC 1.3.5.2 — dihydroorotate dehydrogenase (quinone) (BRENDA: 23 organisms, 120 substrates, 536 inhibitors, 133 Km, 86 kcat entries)

Substrate kinetics (BRENDA)

28 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DIHYDROOROTATE	0.004–0.29	25
DECYLUBIQUINONE	0.0065–0.341	23
S-DIHYDROOROTATE	0.0062–0.115	13
COENZYME QD	0.015–53	12
L-DIHYDROOROTATE	0.015–0.123	12
COENZYME Q1	7.8–48	10
(S)-DIHYDROOROTATE	0.02–0.265	7
COENZYME Q6	0.0011–0.022	4
UBIQUINONE	0.007–0.062	4
UBIQUINONE-6	0.0225–0.062	3
COENZYME Q0	0.17–0.35	2
METHYL DIHYDROOROTATE	0.0154–0.1542	2
UBIQUINONE-0	0.04–0.075	2
UBIQUINONE-50	0.01–0.027	2
1,4-NAPHTHOQUINONE	0.028	1

Catalyzed reactions (Rhea), 1 shown:

• (S)-dihydroorotate + a quinone = orotate + a quinol (RHEA:30187)

UniProt features (70 total): helix 20, strand 15, binding site 13, sequence variant 11, turn 4, topological domain 2, chain 1, transit peptide 1, transmembrane region 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

105 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4OQV	X-RAY DIFFRACTION	1.23
4IGH	X-RAY DIFFRACTION	1.3
9BKN	X-RAY DIFFRACTION	1.3
9EG9	X-RAY DIFFRACTION	1.31
9DHI	X-RAY DIFFRACTION	1.38
9DHG	X-RAY DIFFRACTION	1.39
6OC0	X-RAY DIFFRACTION	1.4
9DHJ	X-RAY DIFFRACTION	1.4
9BKO	X-RAY DIFFRACTION	1.44
9DHH	X-RAY DIFFRACTION	1.49
6QU7	X-RAY DIFFRACTION	1.52
3ZWT	X-RAY DIFFRACTION	1.55
5H2Z	X-RAY DIFFRACTION	1.58
5H73	X-RAY DIFFRACTION	1.58
6FMD	X-RAY DIFFRACTION	1.58
1D3G	X-RAY DIFFRACTION	1.6
3ZWS	X-RAY DIFFRACTION	1.6
5HIN	X-RAY DIFFRACTION	1.6
6J3B	X-RAY DIFFRACTION	1.6
9CZE	X-RAY DIFFRACTION	1.6
9V34	X-RAY DIFFRACTION	1.6
9S1I	X-RAY DIFFRACTION	1.61
5HQE	X-RAY DIFFRACTION	1.62
6CJF	X-RAY DIFFRACTION	1.63
5K9C	X-RAY DIFFRACTION	1.66
5ZF4	X-RAY DIFFRACTION	1.66
3W7R	X-RAY DIFFRACTION	1.68
5K9D	X-RAY DIFFRACTION	1.7
5ZF8	X-RAY DIFFRACTION	1.7
6ET4	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02127-F1	96.13	0.91

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 (1): 214 (nucleophile)

Ligand- & substrate-binding residues (13): 180; 211–216; 211; 254; 282; 283–284; 305; 334; 355–356; 95–99; 99; 119 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-500753	Pyrimidine biosynthesis

MSigDB gene sets: 287 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, chr16q22, MODULE_255, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, MODULE_503, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS

GO Biological Process (6): ‘de novo’ pyrimidine nucleobase biosynthetic process (GO:0006207), UDP biosynthetic process (GO:0006225), pyrimidine ribonucleotide biosynthetic process (GO:0009220), ‘de novo’ UMP biosynthetic process (GO:0044205), pyrimidine nucleotide biosynthetic process (GO:0006221), UMP biosynthetic process (GO:0006222)

GO Molecular Function (6): dihydroorotase activity (GO:0004151), dihydroorotate dehydrogenase activity (GO:0004152), dihydroorotate dehydrogenase (quinone) activity (GO:0106430), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627)

GO Cellular Component (6): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), cytosol (GO:0005829), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nucleotide biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
pyrimidine ribonucleotide biosynthetic process	2
cytoplasm	2
pyrimidine nucleobase biosynthetic process	1
pyrimidine ribonucleoside diphosphate biosynthetic process	1
UDP metabolic process	1
pyrimidine nucleotide biosynthetic process	1
pyrimidine ribonucleotide metabolic process	1
ribonucleotide biosynthetic process	1
UMP biosynthetic process	1
pyrimidine nucleotide metabolic process	1
nucleotide biosynthetic process	1
pyrimidine-containing compound biosynthetic process	1
pyrimidine ribonucleoside monophosphate biosynthetic process	1
UMP metabolic process	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides	1
oxidoreductase activity, acting on the CH-CH group of donors	1
dihydroorotate dehydrogenase activity	1
oxidoreductase activity, acting on the CH-CH group of donors, quinone or related compound as acceptor	1
binding	1
catalytic activity	1
oxidoreductase activity	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHODH	UMPS	P11172	978
DHODH	DHFR2	Q86XF0	908
DHODH	DHFR	P00374	882
DHODH	CAD	P27708	779
DHODH	ETFDH	Q16134	647
DHODH	TYMS	P04818	644
DHODH	IMPDH2	P12268	642
DHODH	CTPS1	P17812	640
DHODH	CYB5R4	Q7L1T6	606
DHODH	PPAT	Q06203	602
DHODH	CTPS2	Q9NRF8	600
DHODH	AIFM2	Q9BRQ8	597
DHODH	TCOF1	Q13428	594
DHODH	CRYZ	Q08257	593
DHODH	GMPS	P49915	590

IntAct

27 interactions, top by confidence:

A	B	Type	Score
TTPA	DHODH	psi-mi:“MI:0915”(physical association)	0.560
DHODH	RNF19B	psi-mi:“MI:0915”(physical association)	0.560
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
TMEM95	EXTL3	psi-mi:“MI:0914”(association)	0.530
SDHC	DHODH	psi-mi:“MI:0915”(physical association)	0.400
MT2A	DHODH	psi-mi:“MI:0915”(physical association)	0.370
DHODH	TMED10	psi-mi:“MI:0915”(physical association)	0.370
VAC14	PIKFYVE	psi-mi:“MI:0914”(association)	0.350
ATAD3A	TMEM223	psi-mi:“MI:0914”(association)	0.350
BST1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
VAC14	NUDT19	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
GMPPB	PRMT3	psi-mi:“MI:0914”(association)	0.350
SDHD	TNNC2	psi-mi:“MI:0914”(association)	0.350
SERBP1	UBA6	psi-mi:“MI:0914”(association)	0.350
TMEM95	CLGN	psi-mi:“MI:0914”(association)	0.350
SDHD	HBB	psi-mi:“MI:0914”(association)	0.350
SFXN1	GPD2	psi-mi:“MI:0914”(association)	0.350
SLC25A16	TOMM70	psi-mi:“MI:0914”(association)	0.350
SLC25A32	CS	psi-mi:“MI:0914”(association)	0.350
TTPA	DHODH	psi-mi:“MI:0915”(physical association)	0.000
DHODH	RNF19B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (47): DHODH (Affinity Capture-MS), DHODH (Affinity Capture-MS), DHODH (Negative Genetic), DHODH (Negative Genetic), DHODH (Negative Genetic), GINS4 (Negative Genetic), HUS1 (Negative Genetic), MRPL32 (Positive Genetic), TAF2 (Negative Genetic), TIPIN (Negative Genetic), DHODH (Affinity Capture-MS), RNF19B (Two-hybrid), TTPA (Two-hybrid), DHODH (Negative Genetic), DHODH (Affinity Capture-MS)

ESM2 similar proteins: A0K0C0, A0L3J9, A0LDN3, A3CUG3, A4X4L9, A5VTK6, A7HH87, A8JGF7, A8M723, A9GD65, A9MDK1, A9WXF1, B1ZY08, B2GKC1, B2SCQ3, B3R684, B8HFS1, B8ZU00, C0RK37, D0EYG3, L0TAD5, O19097, O83641, P0C5D0, P22989, P28624, P63300, P63301, P63302, P63303, Q02127, Q11IW3, Q1D084, Q1IW89, Q2IG40, Q2J717, Q3BUC6, Q568W0, Q579Z7, Q5E9W3

Diamond homologs: A0JX31, A0M4D0, A0PQW5, A0QZY9, A1KKI2, A1SJF2, A1TAT2, A1TZG0, A1UHW0, A1WTJ3, A3PN03, A3Q1C6, A4QEA4, A4TB97, A4X619, A5CS38, A5U4G5, A5UX75, A6Q2V6, A6Q8G0, A6T739, A6V325, A6WD43, A7HD76, A7HQ77, A7NLW9, A8LY18, A9WDI1, B0CA74, B0R808, B0RIK6, B1MPD4, B1W464, B1WUM4, B2GHT4, B2HFZ1, B2IU79, B4STK4, B4UG99, B5EL46

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
MYC	“up-regulates quantity by expression”	DHODH	“transcriptional regulation”
DHODH	“down-regulates quantity”	(S)-dihydroorotate	“chemical modification”
DHODH	“down-regulates quantity”	“coenzyme Q10”	“chemical modification”
DHODH	“up-regulates quantity”	ubiquinol	“chemical modification”
DHODH	“up-regulates quantity”	orotate	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	3
Uncertain significance	97
Likely benign	42
Benign	29

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1075250	NM_001361.5(DHODH):c.248_261del (p.Leu83fs)	Pathogenic
16804	NM_001361.5(DHODH):c.605G>C (p.Gly202Ala)	Pathogenic
16805	NM_001361.5(DHODH):c.605G>A (p.Gly202Asp)	Pathogenic
16807	NM_001361.5(DHODH):c.611del (p.Leu204fs)	Pathogenic
16808	NM_001361.5(DHODH):c.595C>T (p.Arg199Cys)	Pathogenic
2831703	NM_001361.5(DHODH):c.574G>T (p.Glu192Ter)	Pathogenic
3667173	NM_001361.5(DHODH):c.31_46del (p.Gln11fs)	Pathogenic
1301617	NM_001361.5(DHODH):c.952G>T (p.Glu318Ter)	Likely pathogenic
4278090	NM_001361.5(DHODH):c.953A>G (p.Glu318Gly)	Likely pathogenic
4845790	NM_001361.5(DHODH):c.8G>A (p.Trp3Ter)	Likely pathogenic

SpliceAI

2087 predictions. Top by Δscore:

Variant	Effect	Δscore
16:72008786:G:GG	donor_gain	1.0000
16:72014472:GGAA:G	acceptor_gain	1.0000
16:72020700:A:AG	acceptor_gain	1.0000
16:72021307:CCAAG:C	donor_loss	1.0000
16:72021308:CAAGG:C	donor_loss	1.0000
16:72021309:AAGGT:A	donor_loss	1.0000
16:72021310:AGGTG:A	donor_loss	1.0000
16:72021312:G:GA	donor_loss	1.0000
16:72023155:C:A	acceptor_gain	1.0000
16:72023158:A:AG	acceptor_gain	1.0000
16:72023158:ACT:A	acceptor_gain	1.0000
16:72023159:C:G	acceptor_gain	1.0000
16:72023160:T:A	acceptor_gain	1.0000
16:72023160:TGCA:T	acceptor_loss	1.0000
16:72023161:GCAGT:G	acceptor_loss	1.0000
16:72023162:CAGTT:C	acceptor_loss	1.0000
16:72023163:A:AG	acceptor_gain	1.0000
16:72023163:AGT:A	acceptor_loss	1.0000
16:72023163:AGTT:A	acceptor_gain	1.0000
16:72023163:AGTTG:A	acceptor_gain	1.0000
16:72023164:G:GT	acceptor_gain	1.0000
16:72023164:GT:G	acceptor_gain	1.0000
16:72023164:GTT:G	acceptor_gain	1.0000
16:72023164:GTTG:G	acceptor_gain	1.0000
16:72023164:GTTGG:G	acceptor_gain	1.0000
16:72023250:GGC:G	donor_gain	1.0000
16:72023260:G:GT	donor_gain	1.0000
16:72023260:G:T	donor_gain	1.0000
16:72023299:GAT:G	donor_gain	1.0000
16:72023631:GAA:G	donor_gain	1.0000

AlphaMissense

2512 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:72014593:A:C	S119R	0.997
16:72014595:T:A	S119R	0.997
16:72014595:T:G	S119R	0.997
16:72021239:T:A	N211K	0.997
16:72021239:T:G	N211K	0.997
16:72021246:A:C	S214R	0.997
16:72021248:C:A	S214R	0.997
16:72021248:C:G	S214R	0.997
16:72023194:C:A	N283K	0.997
16:72023194:C:G	N283K	0.997
16:72022416:A:G	K254E	0.995
16:72023255:A:C	S304R	0.995
16:72023257:T:A	S304R	0.995
16:72023257:T:G	S304R	0.995
16:72014670:C:A	N144K	0.994
16:72014670:C:G	N144K	0.994
16:72017037:A:C	S150R	0.994
16:72017039:T:A	S150R	0.994
16:72017039:T:G	S150R	0.994
16:72023192:A:T	N283Y	0.994
16:72014591:G:A	G118E	0.993
16:72021146:C:A	N180K	0.993
16:72021146:C:G	N180K	0.993
16:72022418:G:C	K254N	0.993
16:72022418:G:T	K254N	0.993
16:72014638:T:C	F134L	0.992
16:72014640:C:A	F134L	0.992
16:72014640:C:G	F134L	0.992
16:72023193:A:T	N283I	0.992
16:72014519:C:A	A94D	0.991

dbSNP variants (sampled 300 via entrez): RS1000047281 (16:72007302 C>G), RS1000254272 (16:72015425 AG>A), RS1000347145 (16:72015150 C>A,T), RS1000405453 (16:72024658 T>A), RS1000415050 (16:72020653 G>C), RS1000558497 (16:72020825 G>T), RS1000579100 (16:72011456 T>A), RS1000584082 (16:72014913 C>T), RS1000642562 (16:72010110 A>G), RS1000868813 (16:72020831 C>T), RS1001428421 (16:72026312 CAGGAA>C,CAGGAAAGGAA), RS1001513871 (16:72011736 CCCA>C), RS1001615913 (16:72010764 C>G), RS1001703809 (16:72021098 G>A), RS1002014038 (16:72011805 G>A,T)

Disease associations

OMIM: gene MIM:126064 | disease phenotypes: MIM:263750

GenCC curated gene-disease

Disease	Classification	Inheritance
postaxial acrofacial dysostosis	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
postaxial acrofacial dysostosis	Definitive	AR

Mondo (1): postaxial acrofacial dysostosis (MONDO:0009903)

Orphanet (1): Postaxial acrofacial dysostosis (Orphanet:246)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000077	Abnormality of the kidney
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000272	Malar flattening
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000370	Abnormality of the middle ear
HP:0000378	Cupped ear
HP:0000405	Conductive hearing impairment
HP:0000453	Choanal atresia
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000625	Eyelid coloboma
HP:0000656	Ectropion
HP:0000698	Conical tooth
HP:0000767	Pectus excavatum
HP:0001159	Syndactyly
HP:0001374	Congenital hip dislocation
HP:0001510	Growth delay
HP:0001760	Abnormal foot morphology
HP:0002021	Pyloric stenosis
HP:0002558	Supernumerary nipple
HP:0002946	Supernumerary vertebrae
HP:0002974	Radioulnar synostosis
HP:0002984	Hypoplasia of the radius
HP:0003022	Hypoplasia of the ulna

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000253_4	Attention deficit hyperactivity disorder and conduct disorder	7.000000e-06
GCST004122_29	Fibrinogen levels	5.000000e-08
GCST005830_114	Hand grip strength	7.000000e-11
GCST006004_19	Low density lipoprotein cholesterol levels	7.000000e-16
GCST006034_2	Total cholesterol levels	3.000000e-31
GCST006444_8	Bone mineral density (hip)	2.000000e-06
GCST007326_36	Number of sexual partners	2.000000e-10
GCST007565_14	Morning person	2.000000e-15
GCST011346_30	Total cholesterol levels	1.000000e-36
GCST011741_21	LDL cholesterol levels in HIV infection	6.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0007702	hip bone mineral density
EFO:0008328	chronotype measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537680	Genee-Wiedemann syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1966 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 140,755 (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
CHEMBL1450	ATOVAQUONE	4	14,589
CHEMBL960	LEFLUNOMIDE	4	52,218
CHEMBL973	TERIFLUNOMIDE	4	7,575
CHEMBL197194	VIDOFLUDIMUS	3	808
CHEMBL1332971	CLONIXIN	2	10,223
CHEMBL1617398	FLUNIXIN	2	6,952
CHEMBL219376	OXYCINCHOPHEN	2	513
CHEMBL2263632	ASLAN-003	2	357
CHEMBL300058	BREQUINAR SODIUM	2	13,176
CHEMBL38434	BREQUINAR	2	8,144
CHEMBL43185	PIPERINE	2	10,980
CHEMBL63323	NIFLUMIC ACID	2	15,169
CHEMBL4580266	KIO-100	1	51

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3213422	Efficacy	3	leflunomide	Rheumatoid arthritis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3213422	ATP5A1P3, DHODH, PKD1L3	3	0.00	1	leflunomide

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.-.-.- Oxidoreductases

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
orludodstat	Inhibition	8.92	pIC50
S416	Binding	8.77	pKd
compound 19 [PMID: 35925768]	Binding	8.48	pKd
S312	Binding	7.69	pKd
farudodstat	Inhibition	7.46	pIC50
vidofludimus	Inhibition	7.32	pIC50
brequinar	Inhibition	7.0	pKi
teriflunomide	Inhibition	6.51	pIC50
leflunomide	Inhibition	4.89	pKi
BRD9185	Inhibition	4.3	pIC50
DSM421	Inhibition	4.0	pIC50
DSM705	Inhibition	4.0	pIC50

Binding affinities (BindingDB)

311 measured of 372 human assays (391 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(3-chloro-5-methyl-1H-pyrazol-4-yl)-5-fluoro-4-[3-[(1R)-1-hydroxyethyl]-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	IC50	0.22 nM	WO-2022070069: DIHYDROOROTATE DEHYDROGENASE INHIBITORS
N-(3-chloro-5-methyl-1H-pyrazol-4-yl)-5-fluoro-4-[3-[(1S)-1-hydroxyethyl]-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	IC50	0.26 nM	WO-2022070069: DIHYDROOROTATE DEHYDROGENASE INHIBITORS
N-(3-chloro-5-methyl-1H-pyrazol-4-yl)-5-fluoro-4-[3-(2-hydroxypropan-2-yl)-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	IC50	0.38 nM	WO-2022070069: DIHYDROOROTATE DEHYDROGENASE INHIBITORS
3-{[2,3,5,6-tetrafluoro-4-(2-methoxyphenyl)phenyl]carbamoyl}thiophene-2-carboxylic acid	IC50	1 nM
5-cyclopropyl-2-[[6-phenyl-5-(trifluoromethyl)-3-pyridinyl]amino]benzoic acid	IC50	2 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
3-({2,6-difluoro-4-[3-(trifluoromethoxy)phenyl]phenyl}carbamoyl)thiophene-2-carboxylic acid	IC50	2 nM
cyanohydroxybutenamide, 24	KI	2.7 nM
2-[[2-(2-chlorophenyl)pyrimidin-5-yl]amino]-5-cyclopropylbenzoic acid	IC50	3 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
2-[2,3,5,6-tetrafluoro-4-(3-methoxyphenyl)anilino]pyridine-3-carboxylic acid	IC50	3 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
3,6-dimethyl-2-(2,3,5,6-tetrafluoro-4-phenylphenyl)benzimidazole-4-carboxylic acid	IC50	3 nM	US-9006454: Dihydroorotate dehydrogenase inhibitors
3-{[4-(3-ethoxyphenyl)-2,6-difluorophenyl]carbamoyl}thiophene-2-carboxylic acid	IC50	3 nM
6-methyl-2-[2,3,5,6-tetrafluoro-4-(2-fluorophenyl)phenyl]-1H-benzimidazole-4-carboxylic acid	IC50	3.5 nM	US-9006454: Dihydroorotate dehydrogenase inhibitors
2-[[6-(2-chlorophenyl)-3-pyridinyl]amino]-5-cyclopropylbenzoic acid	IC50	4 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
5-cyclopropyl-2-[2,6-difluoro-4-[3-(trifluoromethoxy)phenyl]anilino]pyridine-3-carboxylic acid	IC50	4 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
2-[4-(2-chlorophenyl)-2,6-difluoro-3-methylanilino]pyridine-3-carboxylic acid	IC50	4 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
5-cyclopropyl-2-[[5-methyl-6-[3-(trifluoromethoxy)phenyl]-3-pyridinyl]amino]benzoic acid	IC50	5 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
2-[[6-(2-fluorophenyl)-5-methyl-3-pyridinyl]amino]-5-methylbenzoic acid	IC50	5 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
2-(2,6-difluoro-3-methyl-4-phenylanilino)pyridine-3-carboxylic acid	IC50	5 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
2-[4-(2-chlorophenyl)-2,6-difluoroanilino]-5-cyclopropylpyridine-3-carboxylic acid	IC50	5 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
2-[4-(2,5-dimethylpyrrol-1-yl)-2,3,5,6-tetrafluorophenyl]-6-methyl-1H-benzimidazole-4-carboxylic acid	IC50	5.6 nM	US-9006454: Dihydroorotate dehydrogenase inhibitors
5-cyclopropyl-2-[(5-methyl-6-phenyl-3-pyridinyl)amino]benzoic acid	IC50	6 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
5-cyclopropyl-2-[4-(3-cyclopropyloxyphenyl)-2,6-difluoroanilino]pyridine-3-carboxylic acid	IC50	6 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
2-[2,6-difluoro-3-methyl-4-[3-(trifluoromethoxy)phenyl]anilino]pyridine-3-carboxylic acid	IC50	6 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
6-methyl-2-(2,3,5,6-tetrafluoro-4-phenylphenyl)-1H-benzimidazole-4-carboxylic acid	IC50	6.8 nM	US-9006454: Dihydroorotate dehydrogenase inhibitors
5-cyclopropyl-2-[[6-(3-methoxyphenyl)-5-(trifluoromethyl)-3-pyridinyl]amino]benzoic acid	IC50	7 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
2-({2,3,5,6-tetrafluoro-4-[3-(trifluoromethoxy)phenyl]phenyl}carbamoyl)cyclopent-1-ene-1-carboxylic acid	IC50	7 nM
cyanocyclopropylpropenamide, 11	KI	7 nM
5-cyclopropyl-2-[[6-(2-fluorophenyl)-3-pyridinyl]amino]benzoic acid	IC50	8 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
5-chloro-2-(2,6-difluoro-4-phenylanilino)pyridine-3-carboxylic acid	IC50	8 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
6-fluoro-2-[4-(2-fluorophenyl)phenyl]-3-methylquinoline-4-carboxylic acid	IC50	8 nM
2-{[2,3,5,6-tetrafluoro-4-(2-methoxyphenyl)phenyl]carbamoyl}cyclopent-1-ene-1-carboxylic acid	IC50	8 nM
6-methyl-2-[2,3,5,6-tetrafluoro-4-(3-fluorophenyl)phenyl]-1H-benzimidazole-4-carboxylic acid	IC50	8.86 nM	US-9006454: Dihydroorotate dehydrogenase inhibitors
5-methyl-2-[[5-methyl-6-[3-(pyrrolidine-1-carbonyl)phenyl]-3-pyridinyl]amino]benzoic acid	IC50	9 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
5-cyclopropyl-2-[[2-[2-(trifluoromethyl)phenyl]pyrimidin-5-yl]amino]benzoic acid	IC50	9 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
3-{[4-(2-ethoxyphenyl)-2,6-difluorophenyl]carbamoyl}thiophene-2-carboxylic acid	IC50	9 nM
5-cyclopropyl-2-[(5,6-diphenyl-3-pyridinyl)amino]benzoic acid	IC50	10 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
2-[[6-(3-chlorophenyl)-5-methyl-3-pyridinyl]amino]-5-methylbenzoic acid	IC50	10 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
5-cyclopropyl-2-[[2-(2-fluorophenyl)pyrimidin-5-yl]amino]benzoic acid	IC50	10 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
4-{[4-(2-ethoxyphenyl)-2,6-difluorophenyl]carbamoyl}thiophene-3-carboxylic acid	IC50	10 nM
4-({2,6-difluoro-4-[3-(trifluoromethoxy)phenyl]phenyl}carbamoyl)thiophene-3-carboxylic acid	IC50	10 nM
5-methyl-2-[[5-methyl-6-(3-propan-2-yloxyphenyl)-3-pyridinyl]amino]benzoic acid	IC50	11 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
2-[2,6-difluoro-4-(2-methylphenyl)anilino]pyridine-3-carboxylic acid	IC50	11 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
cyanohydroxybutenamide, 10	KI	11 nM
2-[[6-(3-methoxyphenyl)-5-(trifluoromethyl)-3-pyridinyl]amino]-5-methylbenzoic acid	IC50	12 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
2-[[6-[3-(cyclopropylcarbamoyl)phenyl]-5-methyl-3-pyridinyl]amino]-5-methylbenzoic acid	IC50	12 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
5-cyclopropyl-2-[[2-(2-methylphenyl)pyrimidin-5-yl]amino]benzoic acid	IC50	12 nM	US-8536165: Azabiphenylaminobenzoic acid derivatives as DHODH inhibitors
2-[2,6-difluoro-4-(3-methoxyphenyl)anilino]-5-methylpyridine-3-carboxylic acid	IC50	12 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
2-[2,6-difluoro-4-(3-methoxyphenyl)anilino]-5-ethylpyridine-3-carboxylic acid	IC50	12 nM	US-8691852: Amino nicotinic and isonicotinic acid derivatives as DHODH inhibitors
3-{[3-chloro-4-(2-methoxyphenyl)phenyl]carbamoyl}thiophene-2-carboxylic acid	IC50	12 nM
6-methyl-2-[2,3,5,6-tetrafluoro-4-(3-hydroxyphenyl)phenyl]-1H-benzimidazole-4-carboxylic acid	IC50	13.5 nM	US-9006454: Dihydroorotate dehydrogenase inhibitors

ChEMBL bioactivities

2362 potent at pChembl≥5 of 2558 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	IC50	0.12	nM	CHEMBL4744558
9.75	IC50	0.179	nM	CHEMBL5077700
9.74	IC50	0.18	nM	CHEMBL5405642
9.72	IC50	0.192	nM	CHEMBL5075013
9.72	IC50	0.19	nM	CHEMBL5085549
9.71	IC50	0.195	nM	CHEMBL5083643
9.70	IC50	0.2	nM	CHEMBL4854356
9.70	IC50	0.202	nM	CHEMBL5092899
9.70	IC50	0.2	nM	CHEMBL5180161
9.70	IC50	0.2	nM	CHEMBL5590963
9.66	IC50	0.22	nM	CHEMBL5428953
9.66	IC50	0.22	nM	CHEMBL4791380
9.65	IC50	0.222	nM	CHEMBL4791380
9.65	IC50	0.225	nM	CHEMBL5073905
9.65	IC50	0.226	nM	CHEMBL5882992
9.62	IC50	0.24	nM	CHEMBL5180161
9.62	IC50	0.24	nM	CHEMBL5959164
9.60	IC50	0.249	nM	CHEMBL4753279
9.59	IC50	0.26	nM	CHEMBL5439317
9.59	IC50	0.26	nM	CHEMBL5597054
9.58	IC50	0.265	nM	CHEMBL4745588
9.57	IC50	0.267	nM	CHEMBL4752247
9.57	IC50	0.27	nM	CHEMBL4745588
9.56	IC50	0.273	nM	CHEMBL5781060
9.54	IC50	0.286	nM	CHEMBL5883896
9.54	IC50	0.292	nM	CHEMBL5869293
9.52	IC50	0.3	nM	CHEMBL4852401
9.52	IC50	0.3	nM	CHEMBL5171223
9.52	IC50	0.3	nM	CHEMBL5193821
9.52	IC50	0.3	nM	CHEMBL5437916
9.52	IC50	0.3	nM	CHEMBL6143921
9.49	IC50	0.32	nM	CHEMBL5922923
9.45	IC50	0.356	nM	CHEMBL5596906
9.44	IC50	0.36	nM	CHEMBL5596906
9.42	IC50	0.38	nM	CHEMBL4851260
9.42	IC50	0.38	nM	CHEMBL5431927
9.42	IC50	0.38	nM	CHEMBL5416427
9.40	IC50	0.396	nM	CHEMBL4751399
9.40	IC50	0.4	nM	CHEMBL4859161
9.40	IC50	0.4	nM	CHEMBL4751399
9.39	IC50	0.41	nM	CHEMBL4855859
9.38	IC50	0.42	nM	CHEMBL5598276
9.38	IC50	0.418	nM	CHEMBL5598276
9.37	IC50	0.43	nM	CHEMBL5878639
9.36	IC50	0.44	nM	CHEMBL5598348
9.36	IC50	0.433	nM	CHEMBL5878639
9.36	IC50	0.435	nM	CHEMBL5598348
9.35	IC50	0.45	nM	CHEMBL5409068
9.35	IC50	0.444	nM	CHEMBL6002389
9.34	IC50	0.46	nM	CHEMBL5597274

PubChem BioAssay actives

1023 with measured affinity, of 2894 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
6-fluoro-2-[4-(2-fluorophenyl)phenyl]-N-methoxy-3-methylquinoline-4-carboxamide	1698251: Inhibition of human DHODH	ic50	0.0001	uM
N-(2-chloro-6-fluorophenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-3-carboxamide	1886119: Inhibition of His fused human DHODH expressed in Escherichia coli using DHO as substrate by DCIP absorbance based colorimetry assay	ic50	0.0002	uM
N-(2-chloro-6-fluorophenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-(1,1,1-trifluoropropan-2-yloxy)pyridine-3-carboxamide	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0002	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-2-(2-fluorophenyl)-4-prop-1-en-2-ylisoquinolin-1-one	1685175: Inhibition of human DHODH (30 to 390 residues) expressed in Escherichia coli using dihydroorotate as substrate and CoQ10 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-2-(5-fluoro-2-methylphenyl)-4-prop-1-en-2-ylisoquinolin-1-one	1685175: Inhibition of human DHODH (30 to 390 residues) expressed in Escherichia coli using dihydroorotate as substrate and CoQ10 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
2-(2-chloro-6-fluorophenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-4-propan-2-ylisoquinolin-1-one	1685175: Inhibition of human DHODH (30 to 390 residues) expressed in Escherichia coli using dihydroorotate as substrate and CoQ10 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
4-(6-amino-5-methyl-2-pyridinyl)-N-(2-chloro-6-fluorophenyl)-5-fluoro-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1813836: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
5-fluoro-4-[2-(2-hydroxypropan-2-yl)-1-methylimidazol-4-yl]-N-(2-methylphenyl)-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1813836: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
N-(2-chloro-6-fluorophenyl)-5-fluoro-4-[2-(2-hydroxypropan-2-yl)-1-methylimidazol-4-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1813836: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
4-(6-amino-5-chloro-2-pyridinyl)-5-fluoro-N-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1813836: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
N-(2-chloro-6-fluorophenyl)-5-fluoro-4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1813836: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
2-[4-(2-chloro-6-fluorophenoxy)-8-fluoro-5-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyrido[3,4-d]pyridazin-7-yl]-4-ethyl-5-(hydroxymethyl)-1,2,4-triazol-3-one	1774652: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
6-(6-amino-5-methyl-2-pyridinyl)-7-fluoro-2-(2-methylphenyl)-4-propan-2-ylisoquinolin-1-one	2011751: Inhibition of human DHODH using dihydroorotate and CoQ6 as substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
N-(3-chloro-5-methyl-1H-pyrazol-4-yl)-5-fluoro-4-[3-[(1R)-1-hydroxyethyl]-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	2010110: Inhibition of human DHODH using DHO and CoQ6 as substrate by DCIP dye based spectrophotometric analysis	ic50	0.0002	uM
5-fluoro-4-[2-(2-hydroxypropan-2-yl)-1-methylimidazol-4-yl]-N-[2-(trideuteriomethyl)phenyl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1813836: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0002	uM
N-(3-chloro-2-methoxy-5-methyl-4-pyridinyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-3-carboxamide	1886119: Inhibition of His fused human DHODH expressed in Escherichia coli using DHO as substrate by DCIP absorbance based colorimetry assay	ic50	0.0003	uM
N-(4-chloro-2-methoxy-3-pyridinyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-3-carboxamide	1886119: Inhibition of His fused human DHODH expressed in Escherichia coli using DHO as substrate by DCIP absorbance based colorimetry assay	ic50	0.0003	uM
2-(2-chloro-6-fluorophenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-4-prop-1-en-2-ylisoquinolin-1-one	1685175: Inhibition of human DHODH (30 to 390 residues) expressed in Escherichia coli using dihydroorotate as substrate and CoQ10 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0003	uM
2-(2-chloro-6-fluoro-3-methoxyphenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-4-prop-1-en-2-ylisoquinolin-1-one	1685175: Inhibition of human DHODH (30 to 390 residues) expressed in Escherichia coli using dihydroorotate as substrate and CoQ10 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0003	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-2-(2-methylphenyl)-4-[(2R)-1,1,1-trifluoropropan-2-yl]isoquinolin-1-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0003	uM
N-(2-chloro-6-fluorophenyl)-5-fluoro-4-[3-[(1S)-1-hydroxyethyl]-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	2010110: Inhibition of human DHODH using DHO and CoQ6 as substrate by DCIP dye based spectrophotometric analysis	ic50	0.0003	uM
N-(3-chloro-5-methyl-1H-pyrazol-4-yl)-5-fluoro-4-[3-[(1S)-1-hydroxyethyl]-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	2010110: Inhibition of human DHODH using DHO and CoQ6 as substrate by DCIP dye based spectrophotometric analysis	ic50	0.0003	uM
2-[1-(2-chloro-6-fluoro-3-methoxyphenoxy)-8-[(2S)-1,1,1-trifluoropropan-2-yl]oxyisoquinolin-6-yl]-4-ethyl-5-(hydroxymethyl)-1,2,4-triazol-3-one	1774652: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0003	uM
6-(2-chloro-6-fluorophenyl)-2-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-3-fluoro-8-propan-2-yl-1,6-naphthyridin-5-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0004	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-2-(2-fluoro-6-methylphenyl)-4-propan-2-ylisoquinolin-1-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0004	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-2-(2-methylphenyl)-4-propan-2-ylisoquinolin-1-one	1685175: Inhibition of human DHODH (30 to 390 residues) expressed in Escherichia coli using dihydroorotate as substrate and CoQ10 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0004	uM
2-(2-chlorophenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-4-propan-2-ylisoquinolin-1-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0004	uM
7-fluoro-6-[2-(2-hydroxypropan-2-yl)-1-methylimidazol-4-yl]-2-(2-methylphenyl)-4-propan-2-ylisoquinolin-1-one	2011751: Inhibition of human DHODH using dihydroorotate and CoQ6 as substrate by DCIP dye based spectrophotometry analysis	ic50	0.0004	uM
7-fluoro-6-[2-(2-hydroxypropan-2-yl)-1-methylimidazol-4-yl]-2-(2-methylphenyl)-4-propan-2-ylphthalazin-1-one	2011751: Inhibition of human DHODH using dihydroorotate and CoQ6 as substrate by DCIP dye based spectrophotometry analysis	ic50	0.0004	uM
N-(3-chloro-5-methyl-1H-pyrazol-4-yl)-5-fluoro-4-[3-(2-hydroxypropan-2-yl)-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	2010110: Inhibition of human DHODH using DHO and CoQ6 as substrate by DCIP dye based spectrophotometric analysis	ic50	0.0004	uM
2-[1-[2-chloro-6-fluoro-3-(2-methoxyethoxy)phenoxy]-8-[(2S)-1,1,1-trifluoropropan-2-yl]oxyisoquinolin-6-yl]-4-ethyl-5-(hydroxymethyl)-1,2,4-triazol-3-one	1774652: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0004	uM
2-[4-(2-chloro-6-fluoroanilino)-8-fluoro-5-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyrido[3,4-d]pyridazin-7-yl]-4-ethyl-5-(hydroxymethyl)-1,2,4-triazol-3-one	1774652: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0004	uM
2-[1-[2-chloro-3-(dimethylamino)-6-fluorophenoxy]-8-[(2S)-1,1,1-trifluoropropan-2-yl]oxyisoquinolin-6-yl]-4-ethyl-5-(hydroxymethyl)-1,2,4-triazol-3-one	1774652: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0004	uM
N-(2-chloro-6-fluorophenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-propan-2-yloxypyridine-3-carboxamide	1886119: Inhibition of His fused human DHODH expressed in Escherichia coli using DHO as substrate by DCIP absorbance based colorimetry assay	ic50	0.0005	uM
3-[4-[3-(dimethylamino)phenyl]-3,5-difluorophenyl]benzo[f]benzotriazole-4,9-dione	1657902: Inhibition of human DHODH using dihydroorotate as substrate and CoQ10 as co-substrate preincubated for 30 mins followed by substrate addition by DCIP coupled microplate reader assay	ic50	0.0005	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-2-(4-fluoro-2-methylphenyl)-4-propan-2-ylisoquinolin-1-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0005	uM
2-[2-(difluoromethyl)phenyl]-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-4-propan-2-ylisoquinolin-1-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0005	uM
7-fluoro-6-[2-[(1R)-1-hydroxyethyl]-1-methylimidazol-4-yl]-2-(2-methylphenyl)-4-propan-2-ylisoquinolin-1-one	2011751: Inhibition of human DHODH using dihydroorotate and CoQ6 as substrate by DCIP dye based spectrophotometry analysis	ic50	0.0005	uM
N-(2-chloro-6-fluorophenyl)-5-fluoro-4-[3-[(1R)-1-hydroxyethyl]-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	2010110: Inhibition of human DHODH using DHO and CoQ6 as substrate by DCIP dye based spectrophotometric analysis	ic50	0.0005	uM
N-(2-chloro-6-fluorophenyl)-5-fluoro-4-[3-(2-hydroxypropan-2-yl)-4-methylpyrazol-1-yl]-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzamide	2010110: Inhibition of human DHODH using DHO and CoQ6 as substrate by DCIP dye based spectrophotometric analysis	ic50	0.0005	uM
7-fluoro-6-[2-(2-hydroxypropan-2-yl)-1-(trideuteriomethyl)imidazol-4-yl]-2-(2-methylphenyl)-4-propan-2-ylisoquinolin-1-one	2011751: Inhibition of human DHODH using dihydroorotate and CoQ6 as substrate by DCIP dye based spectrophotometry analysis	ic50	0.0005	uM
6-fluoro-2-[4-(2-fluorophenyl)phenyl]-3-methylquinoline-4-carboxylic acid	1698251: Inhibition of human DHODH	ic50	0.0005	uM
N-(2,4-dichloro-3-pyridinyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-3-carboxamide	1886119: Inhibition of His fused human DHODH expressed in Escherichia coli using DHO as substrate by DCIP absorbance based colorimetry assay	ic50	0.0006	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(2-methoxy-3,5-dimethyl-4-pyridinyl)-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-3-carboxamide	1886119: Inhibition of His fused human DHODH expressed in Escherichia coli using DHO as substrate by DCIP absorbance based colorimetry assay	ic50	0.0006	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-2-(5-fluoro-2-methylphenyl)-4-propan-2-ylisoquinolin-1-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0006	uM
2-(3-chloro-2-methoxy-5-methyl-4-pyridinyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-4-propan-2-ylisoquinolin-1-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0006	uM
2-[8-(2-chloro-6-fluorophenoxy)-4-fluoro-1-(1,1,1-trifluoropropan-2-yloxy)-2,7-naphthyridin-3-yl]-4-ethyl-5-(hydroxymethyl)-1,2,4-triazol-3-one	1774652: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis	ic50	0.0006	uM
7-fluoro-6-[5-(2-hydroxypropan-2-yl)-1-methyl-1,2,4-triazol-3-yl]-2-(2-methylphenyl)-4-propan-2-ylisoquinolin-1-one	2011751: Inhibition of human DHODH using dihydroorotate and CoQ6 as substrate by DCIP dye based spectrophotometry analysis	ic50	0.0006	uM
6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-7-fluoro-4-propan-2-yl-2-[2-(trifluoromethyl)phenyl]isoquinolin-1-one	2119927: Inhibition of recombinant human DHODH followed by DHO substrate by DCIP dye absorbance based spectrophotometric analysis	ic50	0.0007	uM
2-[4-(2,6-difluorophenoxy)-5-methyl-3-propan-2-yloxypyrazol-1-yl]-5-ethylpyrimidine	1196386: Inhibition of His-tagged human DHODH assessed as reduction of DCIP by spectrophotometry	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
teriflunomide	affects reaction, decreases reaction, increases oxidation, decreases activity, decreases expression	3
Acetaminophen	decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
brequinar	decreases activity	2
2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide	affects reaction, decreases reaction, increases oxidation, decreases activity	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Tretinoin	decreases expression	2
4,5-dihydroorotic acid	affects reaction, decreases reaction, increases oxidation	1
lawsone	decreases activity	1
juglone	decreases activity	1
naphthazarin	decreases activity	1
bisphenol A	decreases expression	1
lapachol	decreases activity	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
beta-lapachone	increases expression	1
plumbagin	decreases activity	1
dichloroallyl lawsone	decreases activity	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
1,4-naphthoquinone	decreases activity	1
celastrol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
X 910279	affects reaction, decreases reaction, increases oxidation	1
HR 325	decreases activity	1
malononitrilamide 279	decreases activity	1
polyporic acid	decreases activity	1
K 7174	decreases expression	1

ChEMBL screening assays

297 unique, capped per target: 286 binding, 7 admet, 2 functional, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016137	Binding	Inhibition of human DHODH	Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice. — J Med Chem
CHEMBL4378108	ADMET	Inhibition of human DHODH expressed in Escherichia coli using L-dihydroorotate as substrate	The Development Process for Discovery and Clinical Advancement of Modern Antimalarials. — J Med Chem
CHEMBL4615025	Functional	Inhibition of DHODH in human ARN8 cells assessed as increase in p53 level at 250 nM incubated for 24 hrs in presence of 100 uM de novo pyrimidine ribonucleotide synthesis pathway inhibitor, uridine by Western blot analysis	Optimization of Tetrahydroindazoles as Inhibitors of Human Dihydroorotate Dehydrogenase and Evaluation of Their Activity and In Vitro Metabolic Stability. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7NQ	Ubigene A-549 DHODH KO	Cancer cell line	Male
CVCL_D8K3	Ubigene HCT 116 DHODH KO	Cancer cell line	Male
CVCL_XN24	HAP1 DHODH (-)	Cancer cell line	Male
CVCL_YZ46	A549 DHODH-/-	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04931056	Not specified	COMPLETED	A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.