CYP17A1

Summary

CYP17A1 (cytochrome P450 family 17 subfamily A member 1, HGNC:2593) is a protein-coding gene on chromosome 10q24.32, encoding Steroid 17-alpha-hydroxylase/17,20 lyase (P05093). A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia.

Source: NCBI Gene 1586 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 62
• Clinical variants (ClinVar): 594 total — 79 pathogenic, 44 likely-pathogenic
• Phenotypes (HPO): 68
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000102

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2593
Approved symbol	CYP17A1
Name	cytochrome P450 family 17 subfamily A member 1
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	P450C17, CPT7, S17AH
Ensembl gene	ENSG00000148795
Ensembl biotype	protein_coding
OMIM	609300
Entrez	1586

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000369887, ENST00000469683, ENST00000489268, ENST00000638190, ENST00000638272, ENST00000638971, ENST00000639393, ENST00000640633, ENST00000960106, ENST00000960108, ENST00000960109, ENST00000960110, ENST00000960111, ENST00000960113, ENST00000960114, ENST00000960117, ENST00000960119, ENST00000960120, ENST00000960121, ENST00000960122, ENST00000960123

RefSeq mRNA: 1 — MANE Select: NM_000102 NM_000102

CCDS: CCDS7541

Canonical transcript exons

ENST00000369887 — 8 exons

Exon	Start	End
ENSE00000987437	102835254	102835392
ENSE00000987438	102834785	102835014
ENSE00000987440	102832993	102833208
ENSE00001451179	102830531	102830985
ENSE00001451182	102837065	102837413
ENSE00003301778	102831508	102831611
ENSE00003319035	102832511	102832680
ENSE00003362778	102834036	102834122

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 99.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 9.3198 / max 15158.1646, expressed in 41 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111202	9.2155	31
111201	0.0449	12
111199	0.0231	9
111198	0.0137	3
111204	0.0116	5
111203	0.0069	4
111205	0.0040	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	99.97	gold quality
right adrenal gland cortex	UBERON:0035827	99.97	gold quality
left adrenal gland	UBERON:0001234	99.96	gold quality
adrenal cortex	UBERON:0001235	99.96	gold quality
left adrenal gland cortex	UBERON:0035825	99.96	gold quality
adrenal tissue	UBERON:0018303	99.95	gold quality
adrenal gland	UBERON:0002369	98.83	gold quality
adult organism	UBERON:0007023	87.81	gold quality
adult mammalian kidney	UBERON:0000082	85.84	gold quality
right testis	UBERON:0004534	82.16	gold quality
testis	UBERON:0000473	81.66	gold quality
right uterine tube	UBERON:0001302	81.10	gold quality
right lobe of liver	UBERON:0001114	80.98	gold quality
left testis	UBERON:0004533	80.31	gold quality
right coronary artery	UBERON:0001625	79.69	gold quality
kidney	UBERON:0002113	78.38	gold quality
metanephros cortex	UBERON:0010533	78.02	gold quality
left lobe of thyroid gland	UBERON:0001120	77.20	gold quality
right lobe of thyroid gland	UBERON:0001119	76.42	gold quality
thyroid gland	UBERON:0002046	75.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.53	gold quality
endocervix	UBERON:0000458	73.01	gold quality
left uterine tube	UBERON:0001303	72.88	gold quality
right ovary	UBERON:0002118	72.73	gold quality
cortex of kidney	UBERON:0001225	72.36	gold quality
metanephros	UBERON:0000081	72.05	gold quality
ectocervix	UBERON:0012249	71.69	gold quality
gastrocnemius	UBERON:0001388	71.18	gold quality
liver	UBERON:0002107	70.81	gold quality
nephron tubule	UBERON:0001231	70.69	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-10	no	6.46
E-ANND-3	no	2.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CREB1, DGKQ, ESR1, FOS, FOXL2, GATA4, GATA6, NFIC, NFKB, NONO, NR0B1, NR2F1, NR4A1, NR5A1, NR5A2, PBX1, PIAS1, PRDM8, SFPQ, SMAD3, SMAD7, SOX17, SP1, SP3, SREBF1, TCF3, TFAP2A, TFE3, TRERF1

miRNA regulators (miRDB)

23 targeting CYP17A1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-4730	90.12	69.65	64
HSA-MIR-25-5P	87.02	64.95	84

Literature-anchored findings (GeneRIF, showing 40)

• Investigators examining possible associations between early menarche and mutations in genes of estrogen metabolism found no such association for this gene. (PMID:11749050)
• study provides the first description of 17alpha-hydroxylase activity in adipose tissue and the detection of a new form of the P450c17 cDNA containing a 156 bp in-frame deletion in the first exon (PMID:11834432)
• results support the idea that types 1 and 2 cyt-b5 could be involved in the differential modulation of 17 alpha-hydroxylase and 17,20-lyase activities of P450c17 (PMID:11867265)
• decrease in DHEA and DHEA-S concentrations together with the high F levels that occur in patients with type 2 diabetes mellitus is associated with high 17-hydroxylase (PMID:11888844)
• the hCYP17 promoter showed the formation of three DNA-protein complexes: steroidogenic factor (SF-1) and p54(nrb)/NonO, p54(nrb)/NonO and polypyrimidine tract-binding protein-associated splicing factor (PSF) and SF-1/PSF/p54(nrb)/NonO complex (PMID:11897684)
• CYP17 genetic polymorphism in endometrial cancer (PMID:11911969)
• Association of the CYP17 gene polymorphism with risk of endometriosis in Japanese women. not significantly different between the groups. An increased frequency of the D/D genotype. (PMID:11925378)
• activation of protein phosphatase(s) is essential for cAMP-dependent transcription of human CYP17 (PMID:11956159)
• Protein phosphatase 2A and phosphoprotein SET regulate androgen production by this enzyme. (PMID:12444089)
• CYP17 binding sites for progesterone enantiomers are analyzed (PMID:12464252)
• Differential inhibition of 17alpha-hydroxylase and 17,20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency. (PMID:12466376)
• enhancement of transcription by cAMP-dependent protein kinase via MKP-1 activation in human adrenocortical cells (PMID:12506119)
• cytochrome P450 17alpha-hydroxylase mRNA was detected in the ovarian stroma of all women with endometrial cancer (PMID:12517592)
• Neutralization of positive charges in the redox partner binding surface of CYP17 may be the predominant if not sole mechanism leading to isolated 17,20-lyase deficiency (PMID:12530647)
• A dual-specificity phosphatase, possibly MKP-1, is essential for enhancing hCYP17 transcription in adrenal cortex by desphosphorylating of SF-1, thereby increasing the binding affinity of SF-1, p54nrb, and PSF for hCYP17 promoter. (PMID:12530662)
• CYP17 expressed centrally within fetal zone at 50 days post-conception and later during first trimester. (PMID:12530676)
• the estrogen-metabolizing CYP17 genotype influences age at menarche in healthy postmenopausal Japanese women. (PMID:12574216)
• Results demonstrate that human P450c17 is involved in the biosynthetic pathway leading to the formation of androstenol. (PMID:12631293)
• description of familial occurrence of combined partial 17,20-desmolase and 17alpha-hydroxylase deficiency in phenotypically normal normotensive women who presented with primary infertility, anovulation and persistent cervical dysmucorrhea (PMID:12645864)
• High-activity CYP17 alleles, involved in estrogen formation, were not associated with pubertal stage. (PMID:12692107)
• CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women. (PMID:12971967)
• role of E305G mutation in causing 17,20-lyase deficiency (PMID:14504283)
• insulin stimulates PI3-kinase and extracellular signal-regulated kinase-1/2 activities in human theca cells, but only PI3-kinase mediates the insulin augmentation of forskolin-stimulated 17alpha-hydroxylase activity. (PMID:14512432)
• Deficiency in this enzyme is due to missense-nonsense mutations, and amino acid substitution. (PMID:14552332)
• Deficiency in this enzyme is due to missense/nonsense mutation and amino acid subsitution. (PMID:14552333)
• CYP17 promoter is more active in polycystic ovary syndrome theca cells than in normal theca cells. (PMID:14644808)
• diminished NF-1C-dependent repression may be one mechanism underlying increased basal CYP17 promoter activity and altered gene expression in PCOS (polycystic ovary syndrome) theca cells. (PMID:14684846)
• both cytochrome P450, family 17 and cytochrome P450, family 19 are candidate genes for osteoporosis in postmenopausal women (PMID:14715870)
• Colocalization of CytB5 and P450c17 strongly supports the view that CytB5 plays an important role in the regulation of the androgen biosynthetic pathway in the fetal and adult human. (PMID:14985252)
• African women, homozygous carriers of the CYP17 A2 allele expose their myometrium to a stronger estrogenic stimulation, predisposing to the pathophysiology of uterine leiomyomas. (PMID:14995917)
• CYP17 genetic polymorphism is associated with endometrial cancer (PMID:15072828)
• In conclusion, the A2 allele of the CYP17 T(27)-C polymorphism is associated with reduced bone mass and bone size in lean perimenopausal women, whereas high BMI protects against this negative association. (PMID:15129369)
• CYP1A1-1 (P = 0.004) and CYP1A1-2 (P = 0.03) were found to be associated with significantly decreased and increased risks of breast carcinoma, respectively. (PMID:15241822)
• In contrast to other studies, this study demonstrated in situ expression of CYP17 mRNA and protein in heart tissue. (PMID:15364798)
• Polymorphisms of CYP17 is associated with prostate cancer risk (PMID:15477877)
• No evidence was found for a relationship between common variants of the ERalpha gene and the CYP17 gene with age at natural menopause. (PMID:15539439)
• Arg(347), Arg(358) and Arg(449) are important for activity, cytochrome b(5) promotes conformational changes (PMID:15555906)
• a slower rate of CYP17 mRNA decay contributes to increased steady-state mRNA accumulation and augmented CYP17 gene expression in polycystic ovary theca cells. (PMID:15598676)
• The CYP17 A2 allele is associated with hormone levels, and interacts with insulin levels and diet to affect breast density levels and potentially breast cancer risk. (PMID:15609124)
• Data suggest that cytochrome b5 and phosphorylation enhance 17,20 lyase activity independently of each other, probably by increasing the interaction between P450c17 and NADPH-cytochrome P450 oxidoreductase. (PMID:15687493)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp17a1	ENSDARG00000033566
mus_musculus	Cyp17a1	ENSMUSG00000003555
rattus_norvegicus	Cyp17a1	ENSRNOG00000020035

Protein

Protein identifiers

Steroid 17-alpha-hydroxylase/17,20 lyase — P05093 (reviewed: P05093)

Alternative names: 17-alpha-hydroxyprogesterone aldolase, CYPXVII, Cytochrome P450 17A1, Cytochrome P450-C17, Steroid 17-alpha-monooxygenase

All UniProt accessions (6): P05093, A0A1W2PQ28, A0A1W2PQT5, A0A1W2PRK7, A0A1W2PRY0, Q1HB44

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis. Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol. Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione. Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA. Also 16-alpha hydroxylates androgens, relevant for estriol synthesis. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Post-translational modifications. Phosphorylation is necessary for 17,20-lyase, but not for 17-alpha-hydroxylase activity.

Disease relevance. Adrenal hyperplasia 5 (AH5) [MIM:202110] A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: ‘salt wasting’ (SW, the most severe type), ‘simple virilizing’ (SV, less severely affected patients), with normal aldosterone biosynthesis, ’non-classic form’ or late-onset (NC or LOAH) and ‘cryptic’ (asymptomatic). The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Regulated predominantly by intracellular cAMP levels. The 17,20-lyase activity is stimulated by cytochrome b5, which acts as an allosteric effector increasing the Vmax of the lyase activity.

Pathway. Steroid hormone biosynthesis. Steroid biosynthesis; glucocorticoid biosynthesis.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_000093* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.14.19 — steroid 17alpha-monooxygenase (BRENDA: 19 organisms, 72 substrates, 434 inhibitors, 47 Km, 18 kcat entries)
• EC 1.14.14.32 — 17alpha-hydroxyprogesterone deacetylase (BRENDA: 23 organisms, 68 substrates, 161 inhibitors, 20 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PROGESTERONE	—	20
PREGNENOLONE	0.0001–0.0093	15
17ALPHA-HYDROXYPROGESTERONE	—	8
17ALPHA-HYDROXYPROGESTERONE	0.0005–0.0025	5
17ALPHA-HYDROXYPREGNENOLONE	0.0003–0.0009	4
PROGESTERONE	0.0011–0.0097	4
17-HYDROXYPREGNENOLONE	0.0004–0.0008	3
PREGNENOLONE	0.0005–0.0011	3
17ALPHA-HYDROXYPREGNENOLONE	0.0009–0.0017	2
5ALPHA-PREGNAN-3ALPHA-OL-20-ONE	0.018	1
5ALPHA-PREGNAN-3ALPHA,17ALPHA-DIOL-20-ONE	0.0006	1

Catalyzed reactions (Rhea), 10 shown:

• 17alpha-hydroxyprogesterone + reduced [NADPH–hemoprotein reductase] + O2 = androst-4-ene-3,17-dione + acetate + oxidized [NADPH–hemoprotein reductase] + H2O + 2 H(+) (RHEA:14753)
• progesterone + reduced [NADPH–hemoprotein reductase] + O2 = 17alpha-hydroxyprogesterone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46308)
• 3beta-hydroxyandrost-5-en-17-one + reduced [NADPH–hemoprotein reductase] + O2 = 3beta,16alpha-dihydroxy-androst-5-en-17-one + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:47220)
• pregnenolone + reduced [NADPH–hemoprotein reductase] + O2 = 17alpha-hydroxypregnenolone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:50236)
• 17alpha-hydroxypregnenolone + reduced [NADPH–hemoprotein reductase] + O2 = 3beta-hydroxyandrost-5-en-17-one + acetate + oxidized [NADPH–hemoprotein reductase] + H2O + 2 H(+) (RHEA:50244)
• 17alpha-hydroxyprogesterone + reduced [NADPH–hemoprotein reductase] + O2 = 16alpha,17alpha-dihydroxyprogesterone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53216)
• 16alpha,17alpha-dihydroxyprogesterone + reduced [NADPH–hemoprotein reductase] + O2 = 6beta,16alpha,17alpha-trihydroxyprogesterone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53220)
• 16alpha,17alpha-dihydroxypregnenolone + reduced [NADPH–hemoprotein reductase] + O2 = 3beta,16alpha-dihydroxy-androst-5-en-17-one + acetate + oxidized [NADPH–hemoprotein reductase] + H2O + 2 H(+) (RHEA:53224)
• androst-4-ene-3,17-dione + reduced [NADPH–hemoprotein reductase] + O2 = 16alpha-hydroxyandrost-4-ene-3,17-dione + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53228)
• a C21-steroid + reduced [NADPH–hemoprotein reductase] + O2 = a 17alpha-hydroxy-C21-steroid + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:65760)

UniProt features (78 total): sequence variant 31, helix 22, strand 17, turn 4, binding site 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
6WR1	X-RAY DIFFRACTION	1.85
6WW0	X-RAY DIFFRACTION	2.01
8FDA	X-RAY DIFFRACTION	2.2
5IRQ	X-RAY DIFFRACTION	2.2
5UYS	X-RAY DIFFRACTION	2.39
3SWZ	X-RAY DIFFRACTION	2.4
4NKW	X-RAY DIFFRACTION	2.5
4NKY	X-RAY DIFFRACTION	2.55
3RUK	X-RAY DIFFRACTION	2.6
6CIZ	X-RAY DIFFRACTION	2.6
4NKV	X-RAY DIFFRACTION	2.65
6CIR	X-RAY DIFFRACTION	2.65
6CHI	X-RAY DIFFRACTION	2.7
6WR0	X-RAY DIFFRACTION	2.7
4NKX	X-RAY DIFFRACTION	2.79
4NKZ	X-RAY DIFFRACTION	3
5IRV	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05093-F1	91.86	0.77

Functional residue map

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

Ligand- & substrate-binding residues (2): 202; 442 (axial binding residue)

Mutagenesis-validated functional residues (1):

Position	Phenotype
105	increases the affinity for progesterone, resulting in preferential hydroxylation of progesterone at c17 over c16; increa

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-193048	Androgen biosynthesis
R-HSA-194002	Glucocorticoid biosynthesis
R-HSA-5579028	Defective CYP17A1 causes AH5

MSigDB gene sets: 288 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_GLUCOCORTICOID_METABOLIC_PROCESS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, GOBP_ANDROGEN_BIOSYNTHETIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, TGCTGAY_UNKNOWN, GOBP_HORMONE_BIOSYNTHETIC_PROCESS, GOBP_STEROID_BIOSYNTHETIC_PROCESS, GOBP_GLUCOCORTICOID_BIOSYNTHETIC_PROCESS, GOBP_ANDROGEN_METABOLIC_PROCESS

GO Biological Process (11): steroid biosynthetic process (GO:0006694), androgen biosynthetic process (GO:0006702), glucocorticoid biosynthetic process (GO:0006704), sex differentiation (GO:0007548), steroid metabolic process (GO:0008202), cortisol biosynthetic process (GO:0034651), hormone biosynthetic process (GO:0042446), progesterone metabolic process (GO:0042448), lipid metabolic process (GO:0006629), hormone metabolic process (GO:0042445), olefinic compound metabolic process (GO:0120254)

GO Molecular Function (11): steroid 17-alpha-monooxygenase activity (GO:0004508), iron ion binding (GO:0005506), lyase activity (GO:0016829), oxygen binding (GO:0019825), heme binding (GO:0020037), monooxygenase activity (GO:0004497), steroid hydroxylase activity (GO:0008395), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen (GO:0016712), metal ion binding (GO:0046872)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), axon (GO:0030424), neuronal cell body (GO:0043025), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of steroid hormones	2
Metabolic disorders of biological oxidation enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid hormone biosynthetic process	2
metabolic process	2
catalytic activity	2
oxidoreductase activity	2
monooxygenase activity	2
steroid metabolic process	1
lipid biosynthetic process	1
androgen metabolic process	1
hormone biosynthetic process	1
glucocorticoid metabolic process	1
developmental process involved in reproduction	1
lipid metabolic process	1
glucocorticoid biosynthetic process	1
primary alcohol biosynthetic process	1
cortisol metabolic process	1
ketone biosynthetic process	1
olefinic compound biosynthetic process	1
tertiary alcohol biosynthetic process	1
biosynthetic process	1
hormone metabolic process	1
C21-steroid hormone metabolic process	1
ketone metabolic process	1
olefinic compound metabolic process	1
primary metabolic process	1
regulation of hormone levels	1
steroid hydroxylase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	1
transition metal ion binding	1
small molecule binding	1
tetrapyrrole binding	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
neuron projection	1
somatodendritic compartment	1

Protein interactions and networks

STRING

2688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP17A1	CYB5B	O43169	979
CYP17A1	CYB5A	P00167	978
CYP17A1	HSD3B1	P14060	949
CYP17A1	STAR	P49675	945
CYP17A1	SRD5A1	P18405	929
CYP17A1	HSD3B2	P26439	929
CYP17A1	POR	P16435	912
CYP17A1	HSD17B3	P37058	905
CYP17A1	SRD5A2	P31213	866
CYP17A1	MC2R	Q01718	857
CYP17A1	HSD11B2	P80365	856
CYP17A1	NR5A1	Q13285	849
CYP17A1	DHRS11	Q6UWP2	837
CYP17A1	POMC	P01189	828
CYP17A1	HSD17B1	P14061	822

IntAct

16 interactions, top by confidence:

A	B	Type	Score
CYP17A1	UBA52	psi-mi:“MI:0915”(physical association)	0.400
CYP17A1	ATP5F1E	psi-mi:“MI:0915”(physical association)	0.370
CDO1	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
CYP17A1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.370
CYP17A1	BARX1	psi-mi:“MI:0915”(physical association)	0.370
CYP17A1	RPAIN	psi-mi:“MI:0915”(physical association)	0.370
TIGD7	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
CYP17A1	APC	psi-mi:“MI:0915”(physical association)	0.370
CDH1	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
CHEK2	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
ERBB2	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
IGF1R	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
PTPRJ	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
STK11	CYP17A1	psi-mi:“MI:0915”(physical association)	0.370
KRT80	CYP17A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): CYP17A1 (Two-hybrid), CYP17A1 (Two-hybrid), CYP17A1 (Two-hybrid), CYP17A1 (Two-hybrid), CYP17A1 (Two-hybrid), CYP17A1 (Two-hybrid), CYP17A1 (Two-hybrid), UBA52 (Affinity Capture-MS), CYP17A1 (Affinity Capture-MS), CYP17A1 (Affinity Capture-Western), CYP17A1 (Two-hybrid), HSP90AB1 (Two-hybrid), RPAIN (Two-hybrid), TIGD7 (Two-hybrid), CYP17A1 (Two-hybrid)

ESM2 similar proteins: A0A0G2RKY1, A0A7T9QPT0, B1NF18, B1NF19, B1NF20, B5UAQ8, B9DFU2, C7J3A2, I3QBP4, L7T720, L7T8H2, O46512, P05093, P05185, P0DKI7, P11511, P11715, P19100, P27786, P28649, P70687, Q0DBF4, Q29497, Q29605, Q2XVA1, Q50LH3, Q50LH4, Q54F47, Q54LT7, Q55AJ4, Q5QQX7, Q5Z5R4, Q5Z5R7, Q5Z5S6, Q64410, Q6JD68, Q6QHT9, Q8HYM9, Q8HYN0, Q8HYN1

Diamond homologs: A0A0C6DUU3, A0A166YZU9, A0A179H0I7, A0A1B4XBH1, A0A1E1FFM3, A0A1W5T1U4, A0A2Z4HPZ7, A0A384JQH2, A0A3Q9FEJ4, A0A481WNM6, A0A7T8F1I4, A0A8F4SN83, A2QQU9, A7VMU4, B1GVX3, B2RML6, B3FWR7, B3FWT9, B8MV61, B8NWW3, C5H886, C9K202, D1MX88, D7PHY9, E5A7D8, E9FCP5, F1SY74, G0KYA9, G4N2X2, H2KYS3, L0MXJ1, M2XHZ0, M2YJD1, O13317, P05093, P70687, P79152, P82712, P9WEQ1, P9WEY9

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
abiraterone	down-regulates	CYP17A1	“chemical inhibition”
“abiraterone acetate”	down-regulates	CYP17A1	“chemical inhibition”
6-(7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthalenecarboxamide	down-regulates	CYP17A1	“chemical inhibition”
GATA6	“up-regulates quantity by expression”	CYP17A1	“transcriptional regulation”
CYP17A1	“up-regulates quantity”	dehydroepiandrosterone	“chemical modification”
CYP17A1	“up-regulates quantity”	17alpha-hydroxypregnenolone	“chemical modification”
CYP17A1	“up-regulates quantity”	17alpha-hydroxyprogesterone	“chemical modification”
CYP17A1	“up-regulates quantity”	androst-4-ene-3,17-dione	“chemical modification”
CYP17A1	“down-regulates quantity”	17alpha-hydroxypregnenolone	“chemical modification”
CYP17A1	“down-regulates quantity”	pregnenolone	“chemical modification”
CYP17A1	“down-regulates quantity”	progesterone	“chemical modification”
CYP17A1	“down-regulates quantity”	17alpha-hydroxyprogesterone	“chemical modification”
TFEB	“up-regulates quantity by expression”	CYP17A1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	79
Likely pathogenic	44
Uncertain significance	96
Likely benign	295
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071625	NM_000102.4(CYP17A1):c.802C>T (p.Gln268Ter)	Pathogenic
1072800	NM_000102.4(CYP17A1):c.578del (p.Pro193fs)	Pathogenic
1074306	NM_000102.4(CYP17A1):c.1072C>T (p.Arg358Ter)	Pathogenic
1322182	NM_000102.4(CYP17A1):c.1226C>G (p.Pro409Arg)	Pathogenic
1338524	NM_000102.4(CYP17A1):c.1319G>A (p.Arg440His)	Pathogenic
1412755	NM_000102.4(CYP17A1):c.752del (p.Lys251fs)	Pathogenic
1433585	NM_000102.4(CYP17A1):c.100del (p.Leu34fs)	Pathogenic
1440530	NM_000102.4(CYP17A1):c.1243+1G>T	Pathogenic
1453390	NM_000102.4(CYP17A1):c.41_44del (p.Tyr14fs)	Pathogenic
1454329	NM_000102.4(CYP17A1):c.63del (p.Arg21fs)	Pathogenic
1454523	NC_000010.10:g.(?104592258)(104597718_?)del	Pathogenic
1454713	NM_000102.4(CYP17A1):c.967C>T (p.Gln323Ter)	Pathogenic
1457632	NM_000102.4(CYP17A1):c.1306G>A (p.Gly436Arg)	Pathogenic
1457791	NM_000102.4(CYP17A1):c.548G>A (p.Cys183Tyr)	Pathogenic
1458917	NM_000102.4(CYP17A1):c.603C>A (p.Tyr201Ter)	Pathogenic
1709011	NM_000102.4(CYP17A1):c.438_439del (p.Ile146fs)	Pathogenic
1779	NM_000102.4(CYP17A1):c.353_359dup (p.His120fs)	Pathogenic
1780	NM_000102.4(CYP17A1):c.316T>C (p.Ser106Pro)	Pathogenic
1781	NG_007955.1:g.7152_7674delins469	Pathogenic
1782	NM_000102.4(CYP17A1):c.715C>T (p.Arg239Ter)	Pathogenic
1784	NM_000102.4(CYP17A1):c.1313del (p.Gly438fs)	Pathogenic
1787	NM_000102.4(CYP17A1):c.1040G>A (p.Arg347His)	Pathogenic
1789	NM_000102.4(CYP17A1):c.51G>A (p.Trp17Ter)	Pathogenic
1790	NM_000102.4(CYP17A1):c.436+5G>T	Pathogenic
1791	NM_000102.4(CYP17A1):c.278T>G (p.Phe93Cys)	Pathogenic
1792	NM_000102.4(CYP17A1):c.340T>G (p.Phe114Val)	Pathogenic
1793	NM_000102.4(CYP17A1):c.347A>T (p.Asp116Val)	Pathogenic
1794	NM_000102.4(CYP17A1):c.1039C>T (p.Arg347Cys)	Pathogenic
1795	NM_000102.4(CYP17A1):c.206_230del (p.Gly69fs)	Pathogenic
1796	NM_000102.4(CYP17A1):c.1084C>T (p.Arg362Cys)	Pathogenic

SpliceAI

1167 predictions. Top by Δscore:

Variant	Effect	Δscore
10:102831610:TG:T	acceptor_gain	1.0000
10:102831618:C:CT	acceptor_gain	1.0000
10:102831618:C:T	acceptor_gain	1.0000
10:102831622:G:GC	acceptor_gain	1.0000
10:102834780:CTCA:C	donor_loss	1.0000
10:102834782:CA:C	donor_loss	1.0000
10:102834783:A:T	donor_loss	1.0000
10:102834784:CC:C	donor_loss	1.0000
10:102834786:TTCA:T	donor_gain	1.0000
10:102834932:C:CT	acceptor_gain	1.0000
10:102835010:ACAAA:A	acceptor_gain	1.0000
10:102835011:CAAA:C	acceptor_gain	1.0000
10:102835011:CAAAC:C	acceptor_gain	1.0000
10:102835015:C:CC	acceptor_gain	1.0000
10:102835250:TCACT:T	donor_loss	1.0000
10:102835251:CA:C	donor_loss	1.0000
10:102835252:A:AC	donor_gain	1.0000
10:102835253:C:CC	donor_gain	1.0000
10:102835253:CT:C	donor_gain	1.0000
10:102835253:CTG:C	donor_gain	1.0000
10:102835253:CTGA:C	donor_gain	1.0000
10:102835253:CTGAT:C	donor_gain	1.0000
10:102835257:T:C	donor_gain	1.0000
10:102835388:GTTGC:G	acceptor_gain	1.0000
10:102837061:TTA:T	donor_loss	1.0000
10:102837063:ACC:A	donor_loss	1.0000
10:102830982:CGCT:C	acceptor_gain	0.9900
10:102830984:CT:C	acceptor_gain	0.9900
10:102830986:C:CC	acceptor_gain	0.9900
10:102831501:GACT:G	donor_loss	0.9900

AlphaMissense

3367 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:102830924:G:C	F435L	0.998
10:102830924:G:T	F435L	0.998
10:102830926:A:G	F435L	0.998
10:102832566:G:T	R362S	0.998
10:102833025:A:G	W313R	0.998
10:102833025:A:T	W313R	0.998
10:102834073:C:G	R239P	0.998
10:102835316:C:G	R125P	0.998
10:102830978:G:C	F417L	0.997
10:102830978:G:T	F417L	0.997
10:102830980:A:G	F417L	0.997
10:102832533:G:C	H373D	0.997
10:102832574:T:A	E359V	0.997
10:102831535:A:G	W406R	0.996
10:102831535:A:T	W406R	0.996
10:102830916:C:T	G438E	0.995
10:102832565:C:G	R362P	0.995
10:102832566:G:C	R362G	0.995
10:102834904:A:G	C183R	0.995
10:102837084:A:G	F93S	0.995
10:102837135:A:T	V76D	0.995
10:102830911:G:T	R440S	0.994
10:102831516:A:G	F412S	0.994
10:102831533:C:A	W406C	0.994
10:102831533:C:G	W406C	0.994
10:102835359:C:G	G111R	0.994
10:102837083:G:C	F93L	0.994
10:102837083:G:T	F93L	0.994
10:102837085:A:G	F93L	0.994
10:102837117:G:T	A82D	0.994

dbSNP variants (sampled 300 via entrez): RS1001521465 (10:102835414 G>A,C), RS1001724526 (10:102835446 C>G,T), RS1002147698 (10:102835724 C>A), RS1002592990 (10:102830196 C>T), RS1002671434 (10:102831234 C>T), RS1002694576 (10:102836994 G>A), RS1003588293 (10:102831975 T>A), RS1003700009 (10:102838162 A>G), RS1004467 (10:102834750 A>C,G,T), RS1004607315 (10:102836770 T>C,G), RS1004641499 (10:102836509 G>A), RS1004652430 (10:102837548 G>A,C,T), RS1004884410 (10:102830167 C>A), RS1005529730 (10:102830797 C>T), RS1005579871 (10:102831267 G>C)

Disease associations

OMIM: gene MIM:609300 | disease phenotypes: MIM:202110

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency	Strong	Autosomal recessive
46,XY disorder of sex development due to isolated 17,20-lyase deficiency	Supportive	Autosomal recessive

Mondo (7): congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency (MONDO:0008730), congenital adrenal hyperplasia (MONDO:0018479), 17-alpha-hydroxylase/17,20-lyase deficiency, combined complete (MONDO:0800379), 17-alpha-hydroxylase/17,20-lyase deficiency, combined partial (MONDO:0800380), 17,20-lyase deficiency, isolated (MONDO:0800378), primary ovarian failure (MONDO:0005387), (MONDO:0019597)

Orphanet (4): Congenital adrenal hyperplasia (Orphanet:418), Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency (Orphanet:90793), 46,XY difference of sex development due to isolated 17,20-lyase deficiency (Orphanet:90796), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000026	Male hypogonadism
HP:0000028	Cryptorchidism
HP:0000033	Ambiguous genitalia, male
HP:0000037	Male pseudohermaphroditism
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000138	Ovarian cyst
HP:0000144	Decreased fertility
HP:0000147	Polycystic ovaries
HP:0000151	Aplasia of the uterus
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000815	Hypergonadotropic hypogonadism
HP:0000822	Hypertension
HP:0000823	Delayed puberty
HP:0000837	Increased circulating gonadotropin level
HP:0000840	Adrenogenital syndrome
HP:0000858	Irregular menstruation
HP:0000868	Decreased fertility in females
HP:0000939	Osteoporosis
HP:0001508	Failure to thrive
HP:0001949	Hypokalemic alkalosis
HP:0002215	Sparse axillary hair
HP:0002221	Absent axillary hair
HP:0002225	Sparse pubic hair
HP:0002231	Sparse body hair

GWAS associations

62 associations (top):

Study	Trait	p-value
GCST000393_3	Systolic blood pressure	1.000000e-10
GCST000395_3	Systolic blood pressure	7.000000e-24
GCST000528_8	Parkinson’s disease	7.000000e-08
GCST000998_10	Coronary heart disease	1.000000e-09
GCST001072_2	Blood pressure	4.000000e-17
GCST001074_8	Blood pressure	7.000000e-12
GCST001227_7	Systolic blood pressure	7.000000e-26
GCST001235_11	Blood pressure	8.000000e-11
GCST001236_21	Blood pressure	1.000000e-15
GCST001942_1	Prostate cancer	5.000000e-10
GCST002149_2	Schizophrenia	4.000000e-13
GCST002167_1	Blood pressure	1.000000e-06
GCST002289_22	Coronary artery disease	1.000000e-06
GCST002539_4	Schizophrenia	6.000000e-19
GCST002627_9	Hypertension	7.000000e-13
GCST002630_10	Systolic blood pressure	6.000000e-17
GCST002631_14	Diastolic blood pressure	6.000000e-13
GCST003116_37	Coronary artery disease	5.000000e-09
GCST003117_1	Myocardial infarction	8.000000e-08
GCST003253_11	Microalbuminuria	6.000000e-06
GCST003272_3	Systolic blood pressure	3.000000e-09
GCST003272_5	Systolic blood pressure	1.000000e-07
GCST003275_10	Mean arterial pressure	2.000000e-06
GCST003799_7	Colorectal cancer	8.000000e-12
GCST004065_25	Waist circumference	4.000000e-08
GCST004066_110	Hip circumference	2.000000e-08
GCST004066_38	Hip circumference	4.000000e-06
GCST004279_29	Systolic blood pressure	5.000000e-11
GCST004521_172	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_78	Autism spectrum disorder or schizophrenia	1.000000e-16

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009282	sodium measurement
EFO:0006527	smoking status measurement
EFO:0004344	birth weight
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000312	Adrenal Hyperplasia, Congenital	C12.050.351.875.253.090.500; C12.200.706.316.090.500; C12.800.316.090.500; C16.131.939.316.129.500; C16.320.033; C16.320.565.925.249; C18.452.648.925.249; C19.053.440; C19.391.119.090.500
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3522 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 361,612 (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
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1170	TESTOSTERONE PROPIONATE	4	17,619
CHEMBL1200438	TIOCONAZOLE	4	15,162
CHEMBL1397	POSACONAZOLE	4	541
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL1571863	ISOCONAZOLE	4	12,144
CHEMBL254328	ABIRATERONE	4	22,316
CHEMBL271227	ABIRATERONE ACETATE	4	2,610
CHEMBL277535	BIFONAZOLE	4	12,513
CHEMBL3099695	OSILODROSTAT	4	347
CHEMBL488	AMINOGLUTETHIMIDE	4	74,271
CHEMBL808	ECONAZOLE	4	24,813
CHEMBL91	MICONAZOLE	4	45,914
CHEMBL1921976	ORTERONEL	3	602
CHEMBL2105738	GALETERONE	3	971
CHEMBL70611	AZALANSTAT	2	103

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs743572	CYP17A1		0.00	0
rs2486758	CYP17A1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP11, CYP17, CYP19, CYP20 and CYP21 families

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
abiraterone-C6 oxime	Inhibition	7.78	pIC50
orteronel	Inhibition	7.72	pIC50
levoketoconazole	Inhibition	7.42	pKi
abiraterone	Inhibition	7.3	pIC50
YXG-158	Inhibition	7.0	pIC50
galeterone	Inhibition	6.52	pIC50
seviteronel	Inhibition	6.17	pIC50

Binding affinities (BindingDB)

390 measured of 432 human assays (432 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(1S,2R,5S,7S,11S,12S,16S)-5-hydroxy-2,16-dimethyl-15-pyridin-3-yl-8-azatetracyclo[9.7.0.02,7.012,16]octadec-14-en-8-yl]ethanone	IC50	1 nM	US-9611270: Inhibitors of CYP17A1
7-(4-methyl-3-pyridinyl)-3-phenyl-1,2-benzoxazole	IC50	1.1 nM	US-8969586: Substituted bicyclic heteroaryl compounds
3-[[(8S,9S,13S,14S)-17-(5-fluoro-3-pyridinyl)-13-methyl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthrene-3-carbonyl]-methylamino]propanoic acid	IC50	1.3 nM	US-9487554: Estra-1,3,5(10),16-tetraene-3-carboxamide derivatives, processes for their preparation, pharmaceutical preparations comprising them and their use for preparing medicaments
N-[3-methyl-4-[4-(2,2,2-trifluoroethoxy)-3-pyridinyl]phenyl]methanesulfonamide	IC50	1.4 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
1-(4-cyclopropyl-3-pyridinyl)-3-(2,6-dichloro-4-pyridinyl)imidazolidin-2-one	IC50	1.9 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
N-[4-(4-cyclopropyl-3-pyridinyl)-3-methoxyphenyl]methanesulfonamide	IC50	2.1 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
3-[(R)-1H-imidazol-1-yl(4-nitrophenyl)methyl]-4H-chromen-4-one	IC50	2.3 nM
USRE45173, 121A	IC50	2.5 nM	US-RE45173
N-[3-methoxy-4-(4-methyl-3-pyridinyl)phenyl]methanesulfonamide	IC50	2.5 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
USRE45173, 192A	IC50	2.7 nM	US-RE45173
N-(4-isoquinolin-4-yl-3-methoxyphenyl)-4-methoxybenzenesulfonamide	IC50	2.7 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
1-(4-cyclopropyl-3-pyridinyl)-3-(3-methyl-1-benzofuran-5-yl)imidazolidin-2-one	IC50	2.7 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
N-(4-isoquinolin-4-yl-3-methoxyphenyl)benzenesulfonamide	IC50	2.9 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
USRE45173, 29A	IC50	3 nM	US-RE45173
(3S,6S,8R,9S,10R,13S,14S)-10,13-dimethyl-6-(methylamino)-17-pyridin-3-yl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	IC50	3 nM	US-9611270: Inhibitors of CYP17A1
N-[4-isoquinolin-4-yl-3-(trifluoromethoxy)phenyl]methanesulfonamide	IC50	3.2 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
3-(4-fluorophenyl)-7-(4-methyl-3-pyridinyl)-1,2-benzoxazole	IC50	3.2 nM	US-8969586: Substituted bicyclic heteroaryl compounds
Adamantane-1-carboxylic acid (S)-1-pyridin-4-yl-ethyl ester	IC50	3.3 nM
USRE45173, 196A	IC50	3.4 nM	US-RE45173
1-(4-chlorophenyl)-N-[3-methoxy-4-(4-methylpyrimidin-5-yl)phenyl]methanesulfonamide	IC50	3.4 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
3-[[(8S,9S,13S,14S)-17-(5-fluoro-3-pyridinyl)-13-methyl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthrene-3-carbonyl]amino]-2,2-dimethylpropanoic acid	IC50	3.6 nM	US-9487554: Estra-1,3,5(10),16-tetraene-3-carboxamide derivatives, processes for their preparation, pharmaceutical preparations comprising them and their use for preparing medicaments
3-(4-fluorophenyl)-7-(4-methyl-3-pyridinyl)-[1,2]oxazolo[4,5-b]pyridine	IC50	3.9 nM	US-8969586: Substituted bicyclic heteroaryl compounds
USRE45173, 28A	IC50	4 nM	US-RE45173
7-(4-cyclopropylpyrimidin-5-yl)-3-(4-fluorophenyl)thieno[3,2-b]pyridine	IC50	4 nM	US-8969586: Substituted bicyclic heteroaryl compounds
5-[3-(2-chloro-4-fluorophenyl)thieno[3,2-b]pyridin-7-yl]pyrimidin-4-amine	IC50	4 nM	US-8969586: Substituted bicyclic heteroaryl compounds
6-[(7S)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide	IC50	4 nM	US-9611270: Inhibitors of CYP17A1
USRE45173, 91A	IC50	4.3 nM	US-RE45173
1-(4-cyclopropyl-3-pyridinyl)-3-[2-cyclopropyl-6-(trifluoromethyl)-4-pyridinyl]imidazolidin-2-one	IC50	4.75 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
2-[[(8S,9S,13S,14S)-17-(5-fluoro-3-pyridinyl)-13-methyl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthrene-3-carbonyl]amino]acetic acid	IC50	4.9 nM	US-9487554: Estra-1,3,5(10),16-tetraene-3-carboxamide derivatives, processes for their preparation, pharmaceutical preparations comprising them and their use for preparing medicaments
USRE45173, 90A	IC50	5 nM	US-RE45173
1-[2-chloro-6-(trifluoromethyl)-4-pyridinyl]-3-(4-cyclopropyl-3-pyridinyl)imidazolidin-2-one	IC50	5 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
(1S,2R,5S,7S,11S,12S,16S)-5-hydroxy-2,16-dimethyl-15-pyridin-3-yl-8-azatetracyclo[9.7.0.02,7.012,16]octadec-14-en-9-one	IC50	5 nM	US-9611270: Inhibitors of CYP17A1
1-(2-chloro-6-cyclopropyl-4-pyridinyl)-3-(4-cyclopropyl-3-pyridinyl)imidazolidin-2-one	IC50	5.2 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
N-[3-methoxy-4-(4-methylpyrimidin-5-yl)phenyl]benzenesulfonamide	IC50	5.4 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
4-(4-methyl-3-pyridinyl)-1-pyridin-2-ylbenzimidazole	IC50	5.8 nM	US-9133160: Substituted benzimidazole and imidazopyridine compounds useful as CYP17 modulators
USRE45173, 16A	IC50	6 nM	US-RE45173
N-(4-isoquinolin-4-yl-3-methoxyphenyl)pyridine-2-sulfonamide	IC50	6 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
1-(4-cyclopropyl-3-pyridinyl)-3-[3-(trifluoromethyl)phenyl]imidazolidin-2-one	IC50	6 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
(1S,5R)-2-(2-chloro-4-pyridinyl)-4-(4-cyclopropyl-3-pyridinyl)-2,4-diazabicyclo[3.1.0]hexan-3-one	IC50	6 nM	US-9029399: 17α-hydroxylase/C17,20-lyase inhibitors
1-[2,6-bis(trifluoromethyl)-4-pyridinyl]-3-(4-cyclopropyl-3-pyridinyl)imidazolidin-2-one	IC50	6 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
BDBM158452	IC50	6 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
N-(4-isoquinolin-4-yl-3-methoxyphenyl)cyclopropanesulfonamide	IC50	6.2 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
USRE45173, 70A	IC50	6.5 nM	US-RE45173
N-(4-isoquinolin-4-yl-3-methoxyphenyl)methanesulfonamide	IC50	6.6 nM	US-8916553: Sulfonamide compounds useful as CYP17 inhibitors
1-(4-cyclopropyl-3-pyridinyl)-3-(3-methyl-1-benzothiophen-5-yl)imidazolidin-2-one	IC50	6.7 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
(1R,5S)-2-(4-cyclopropyl-3-pyridinyl)-4-[2-(trifluoromethyl)-4-pyridinyl]-2,4-diazabicyclo[3.1.0]hexan-3-one	IC50	6.9 nM	US-9029399: 17α-hydroxylase/C17,20-lyase inhibitors
USRE45173, 152A	IC50	7 nM	US-RE45173
1-(1-benzothiophen-6-yl)-3-(4-cyclopropyl-3-pyridinyl)imidazolidin-2-one	IC50	7 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
1-(4-cyclopropyl-3-pyridinyl)-3-(5-fluoro-1-benzothiophen-2-yl)imidazolidin-2-one	IC50	7 nM	US-9339501: 17a-hydroxylase/C17,20-lyase inhibitors
USRE45173, 102A	IC50	7.5 nM	US-RE45173

ChEMBL bioactivities

1068 potent at pChembl≥5 of 1089 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.77	IC50	0.017	nM	CHEMBL4130227
9.14	IC50	0.73	nM	CHEMBL3913908
9.00	IC50	1	nM	CHEMBL4127656
9.00	IC50	1	nM	CHEMBL4126996
9.00	IC50	1	nM	CHEMBL3696099
9.00	IC50	1	nM	CHEMBL4276910
8.96	IC50	1.1	nM	CHEMBL3696099
8.92	Ki	1.2	nM	CHEMBL2392006
8.92	Ki	1.2	nM	CHEMBL74661
8.85	Ki	1.4	nM	CHEMBL3415119
8.85	IC50	1.4	nM	CHEMBL3666697
8.85	Ki	1.4	nM	CHEMBL78108
8.74	IC50	1.8	nM	CHEMBL110524
8.74	IC50	1.8	nM	CHEMBL310662
8.72	Ki	1.9	nM	CHEMBL3415124
8.72	IC50	1.9	nM	CHEMBL3677969
8.72	Ki	1.9	nM	CHEMBL310336
8.70	IC50	2	nM	CHEMBL3782020
8.70	IC50	2	nM	CHEMBL4128368
8.70	IC50	2	nM	CHEMBL4285546
8.70	IC50	2	nM	ABIRATERONE
8.70	IC50	2	nM	CHEMBL5284599
8.68	IC50	2.1	nM	CHEMBL3666702
8.68	IC50	2.1	nM	CHEMBL432751
8.60	IC50	2.5	nM	CHEMBL3666698
8.60	IC50	2.5	nM	ABIRATERONE ACETATE
8.60	IC50	2.5	nM	CHEMBL79829
8.59	IC50	2.6	nM	CHEMBL310662
8.57	IC50	2.7	nM	CHEMBL112908
8.57	IC50	2.7	nM	CHEMBL3677940
8.57	IC50	2.7	nM	CHEMBL3662060
8.55	IC50	2.8	nM	CHEMBL432751
8.54	IC50	2.9	nM	CHEMBL3662058
8.54	IC50	2.9	nM	CHEMBL311444
8.54	IC50	2.9	nM	ABIRATERONE
8.52	Ki	3	nM	CHEMBL2111951
8.52	IC50	3	nM	CHEMBL3780658
8.52	IC50	3	nM	CHEMBL4289969
8.52	IC50	3	nM	CHEMBL5286021
8.52	IC50	3	nM	CHEMBL5290743
8.52	IC50	3	nM	CHEMBL112908
8.52	IC50	3	nM	CHEMBL5852196
8.52	IC50	3	nM	CHEMBL84230
8.52	IC50	3	nM	CHEMBL432751
8.49	IC50	3.2	nM	CHEMBL3666703
8.49	IC50	3.2	nM	CHEMBL3696101
8.48	IC50	3.3	nM	CHEMBL110524
8.47	IC50	3.4	nM	CHEMBL3666692
8.46	IC50	3.5	nM	CHEMBL4284756
8.43	IC50	3.7	nM	CHEMBL3922888

PubChem BioAssay actives

722 with measured affinity, of 1717 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
1-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-ethylsulfonylpiperazine	1328449: Inhibition of recombinant CYP17 (unknown origin) overexpressed in human AD293 cells using [21-3H]17alpha-hydroxyl-pregenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs by Topcount method	ic50	0.0007	uM
1-[4-[(E)-2-(3-fluoro-5-pyridin-4-ylphenyl)ethenyl]phenyl]-4-propan-2-ylsulfonylpiperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0010	uM
1-cyclopropylsulfonyl-4-[4-[(E)-2-(3-fluoro-5-pyridin-4-ylphenyl)ethenyl]phenyl]piperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0010	uM
7-(4-methyl-3-pyridinyl)-3-phenyl-1,2-benzoxazole	1921661: Inhibition of human CYP17A1	ic50	0.0010	uM
(3S,8R,9S,10R,13S,14S)-17-imidazol-1-yl-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol	1199393: Inhibition of human CYP17 using 17alpha-hydroxypregnenolone substrate	ki	0.0012	uM
(3S,10R,13S)-17-imidazol-1-yl-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol	53239: Binding affinity for Cytochrome P450 17A1 (17-alpha-hydroxypregnenolone Km=560 nM)	ki	0.0012	uM
(3S,10R,13S)-10,13-dimethyl-17-(triazol-1-yl)-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol	53239: Binding affinity for Cytochrome P450 17A1 (17-alpha-hydroxypregnenolone Km=560 nM)	ki	0.0014	uM
(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(triazol-1-yl)-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol	1199393: Inhibition of human CYP17 using 17alpha-hydroxypregnenolone substrate	ki	0.0014	uM
(13S)-13-methyl-17-pyridin-3-yl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-3-ol	53248: Ability to inhibit the C17,20-lyase enzyme by 50% using 17-alpha-hydroxyprogesterone as substrate.	ic50	0.0018	uM
[(1S)-1-pyridin-4-ylethyl] adamantane-1-carboxylate	53376: Inhibition of C17,20-lyase enzyme, cytochrome P450 17A1 in Human testicular microsomes	ic50	0.0018	uM
(8R,9S,10R,13S,14S)-17-imidazol-1-yl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one	1199393: Inhibition of human CYP17 using 17alpha-hydroxypregnenolone substrate	ki	0.0019	uM
(10R,13S)-17-imidazol-1-yl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one	53239: Binding affinity for Cytochrome P450 17A1 (17-alpha-hydroxypregnenolone Km=560 nM)	ki	0.0019	uM
4-(4-methyl-3-pyridinyl)-1-pyridin-2-ylindazole	1286707: Inhibition of human CYP17A1 expressed in HEK293 cell microsomes using [3H]-pregnenolone as substrate incubated for 45 mins by scintillation proximity assay in presence of NADPH	ic50	0.0020	uM
Abiraterone	1864638: Inhibition of human recombinant CYP17A1 incubated for 5 mins in presence of NADPH by LC-MS/MS analysis	ic50	0.0020	uM
7-(4-methyl-3-pyridinyl)-3-phenylpyrazolo[1,5-a]pyridine	1921661: Inhibition of human CYP17A1	ic50	0.0020	uM
1-[4-[(E)-2-(3-fluoro-5-pyridin-4-ylphenyl)ethenyl]phenyl]-4-(trifluoromethylsulfonyl)piperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0020	uM
(10R,13S)-10,13-dimethyl-17-pyridin-3-yl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one	53248: Ability to inhibit the C17,20-lyase enzyme by 50% using 17-alpha-hydroxyprogesterone as substrate.	ic50	0.0021	uM
(3R,5S,10S,13S)-10,13-dimethyl-17-pyridin-3-yl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	53248: Ability to inhibit the C17,20-lyase enzyme by 50% using 17-alpha-hydroxyprogesterone as substrate.	ic50	0.0025	uM
Abiraterone Acetate	2061622: Inhibition of human CYP17A1 17-alpha hydroxylase activity	ic50	0.0025	uM
2-pyridin-4-ylpropan-2-yl adamantane-1-carboxylate	53376: Inhibition of C17,20-lyase enzyme, cytochrome P450 17A1 in Human testicular microsomes	ic50	0.0027	uM
(10R,13S)-10,13-dimethyl-17-pyridin-3-yl-2,6,7,8,9,12,14,15-octahydro-1H-cyclopenta[a]phenanthrene-3,11-dione	53248: Ability to inhibit the C17,20-lyase enzyme by 50% using 17-alpha-hydroxyprogesterone as substrate.	ic50	0.0029	uM
(3S,8R,9S,10R,13R,17S)-17-[(2S)-aziridin-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol	53219: Binding affinity for Cytochrome P450 17 from human testicular microsomes	ki	0.0030	uM
4-(4-methyl-3-pyridinyl)-1-pyridazin-3-ylindazole	1286707: Inhibition of human CYP17A1 expressed in HEK293 cell microsomes using [3H]-pregnenolone as substrate incubated for 45 mins by scintillation proximity assay in presence of NADPH	ic50	0.0030	uM
4-methyl-3-(3-phenyl-1-benzothiophen-7-yl)pyridine	1921661: Inhibition of human CYP17A1	ic50	0.0030	uM
(5S,10S,13S)-10,13-dimethyl-17-pyridin-3-yl-1,2,4,5,6,7,8,9,11,12,14,15-dodecahydrocyclopenta[a]phenanthren-3-one	53248: Ability to inhibit the C17,20-lyase enzyme by 50% using 17-alpha-hydroxyprogesterone as substrate.	ic50	0.0030	uM
1-(3-methoxyphenyl)-4-(4-methyl-3-pyridinyl)pyrazolo[3,4-b]pyridine	1921661: Inhibition of human CYP17A1	ic50	0.0030	uM
1-cyclopropylsulfonyl-4-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine	1328449: Inhibition of recombinant CYP17 (unknown origin) overexpressed in human AD293 cells using [21-3H]17alpha-hydroxyl-pregenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs by Topcount method	ic50	0.0037	uM
1-[(5-bromo-1-benzofuran-2-yl)-(2-chlorophenyl)methyl]imidazole	1989630: Inhibition of human testis C17, 20 lyase activity using 17alpha-[1,2-3H] hydroxyprogesterone incubated for 30 mins in presence of NADPH generating system	ic50	0.0040	uM
2-[4-(4-methyl-3-pyridinyl)indazol-1-yl]-1,3-thiazole	1286707: Inhibition of human CYP17A1 expressed in HEK293 cell microsomes using [3H]-pregnenolone as substrate incubated for 45 mins by scintillation proximity assay in presence of NADPH	ic50	0.0040	uM
4-(4-methyl-3-pyridinyl)-1-phenylindazole	1286707: Inhibition of human CYP17A1 expressed in HEK293 cell microsomes using [3H]-pregnenolone as substrate incubated for 45 mins by scintillation proximity assay in presence of NADPH	ic50	0.0040	uM
1-(2-chloro-4-fluorophenyl)-4-(4-methyl-3-pyridinyl)pyrazolo[3,4-b]pyridine	1921661: Inhibition of human CYP17A1	ic50	0.0040	uM
4-[4-(3,3-difluoroazetidin-1-yl)pyrimidin-5-yl]-1-(4-fluorophenyl)pyrazolo[3,4-b]pyridine	1921661: Inhibition of human CYP17A1	ic50	0.0040	uM
1-[1-(9H-fluoren-2-yl)ethyl]imidazole	362257: Inhibition of CYP17	ic50	0.0040	uM
1-[4-[4-[(E)-2-(3-fluoro-5-pyridin-4-ylphenyl)ethenyl]phenyl]piperazin-1-yl]ethanone	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0046	uM
(3S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-pyridin-3-yl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol	161639: Inhibition of human progesterone 17-alpha-hydroxylase.	ic50	0.0050	uM
1-[4-[(E)-2-(3-fluoro-5-pyridin-4-ylphenyl)ethenyl]phenyl]-4-methylsulfonylpiperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
1-[4-[4-[(E)-2-(3-chloro-5-pyridin-4-ylphenyl)ethenyl]phenyl]piperazin-1-yl]ethanone	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
1-[4-[(E)-2-(3-chloro-5-pyridin-4-ylphenyl)ethenyl]phenyl]-4-propan-2-ylsulfonylpiperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
1-[4-[(E)-2-(3-chloro-5-pyridin-4-ylphenyl)ethenyl]phenyl]-4-methylsulfonylpiperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
1-[4-[(E)-2-(3-chloro-5-pyridin-4-ylphenyl)ethenyl]phenyl]-4-cyclopropylsulfonylpiperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
2-[4-[4-[(E)-2-(3-chloro-5-pyridin-4-ylphenyl)ethenyl]phenyl]piperazin-1-yl]-4,5-dihydro-1,3-oxazole	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
1-ethylsulfonyl-4-[4-[(E)-2-(3-fluoro-5-pyridin-4-ylphenyl)ethenyl]phenyl]piperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
2-[4-[4-[(E)-2-(3-fluoro-5-pyridin-4-ylphenyl)ethenyl]phenyl]piperazin-1-yl]-4,5-dihydro-1,3-oxazole	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
1-(4-fluorophenyl)-4-(4-methyl-3-pyridinyl)indazole	1286707: Inhibition of human CYP17A1 expressed in HEK293 cell microsomes using [3H]-pregnenolone as substrate incubated for 45 mins by scintillation proximity assay in presence of NADPH	ic50	0.0050	uM
4-(4-methyl-3-pyridinyl)-1-pyrazin-2-ylindazole	1286707: Inhibition of human CYP17A1 expressed in HEK293 cell microsomes using [3H]-pregnenolone as substrate incubated for 45 mins by scintillation proximity assay in presence of NADPH	ic50	0.0050	uM
4-[4-(4-methyl-3-pyridinyl)indazol-1-yl]-1,3-thiazole	1286707: Inhibition of human CYP17A1 expressed in HEK293 cell microsomes using [3H]-pregnenolone as substrate incubated for 45 mins by scintillation proximity assay in presence of NADPH	ic50	0.0050	uM
1-[4-[(E)-2-(3-chloro-5-pyridin-4-ylphenyl)ethenyl]phenyl]-4-(difluoromethylsulfonyl)piperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
1-(difluoromethylsulfonyl)-4-[4-[(E)-2-(3-fluoro-5-pyridin-4-ylphenyl)ethenyl]phenyl]piperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
1-(difluoromethylsulfonyl)-4-[4-[(E)-2-[3-fluoro-5-(imidazol-1-ylmethyl)phenyl]ethenyl]phenyl]piperazine	1497274: Inhibition of recombinant CYP17 (unknown origin) expressed in human AD293 cells using [21-3H]17alpha-hydroxypregnenolone as substrate preincubated for 60 mins followed by substrate addition measured after 4 hrs Topcount method	ic50	0.0050	uM
4-(4-methyl-3-pyridinyl)-7-phenylpyrrolo[1,2-b]pyridazine	1921661: Inhibition of human CYP17A1	ic50	0.0050	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Colforsin	decreases reaction, increases expression, affects cotreatment, decreases expression	11
Androstenedione	increases metabolic processing, decreases reaction, decreases expression, affects abundance, affects response to substance (+2 more)	7
Ketoconazole	decreases expression, decreases reaction, increases expression, decreases activity	7
Pregnenolone	increases chemical synthesis, affects metabolic processing, increases hydroxylation, decreases reaction, decreases activity (+1 more)	6
Progesterone	decreases reaction, decreases activity, decreases hydroxylation, increases chemical synthesis, affects metabolic processing (+2 more)	6
bisphenol A	decreases reaction, decreases activity, decreases expression, increases expression, affects response to substance	5
Resveratrol	affects cotreatment, decreases expression, decreases activity	4
Dehydroepiandrosterone	affects chemical synthesis, increases chemical synthesis, increases metabolic processing, decreases expression, decreases reaction	4
17-alpha-Hydroxypregnenolone	increases hydroxylation, decreases reaction, decreases activity, decreases hydroxylation, affects chemical synthesis (+4 more)	4
Valproic Acid	decreases reaction, increases expression, decreases expression	4
8-Bromo Cyclic Adenosine Monophosphate	affects cotreatment, decreases expression, increases expression, decreases reaction	4
17-alpha-Hydroxyprogesterone	increases hydroxylation, decreases reaction, decreases activity, affects abundance, affects chemical synthesis (+4 more)	4
Flame Retardants	decreases expression, increases expression	3
Testosterone	affects abundance, affects response to substance, decreases expression	3
androsta-5,16-dien-3 beta-ol	decreases activity, affects chemical synthesis	2
3,4,5,3’,4’-pentachlorobiphenyl	decreases activity, decreases expression, increases expression	2
prochloraz	decreases expression, decreases activity	2
perfluorooctane sulfonic acid	affects abundance, affects response to substance, decreases expression	2
abiraterone	decreases activity, decreases hydroxylation, increases chemical synthesis	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases activity, increases expression, decreases reaction, decreases activity, increases reaction	2
bifenthrin	increases expression, decreases expression, decreases reaction	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases activity, decreases expression	2
bisphenol S	decreases expression, increases expression	2
bisphenol AF	decreases expression	2
Pioglitazone	increases expression, decreases activity, decreases expression, decreases reaction, increases activity	2
Carbamazepine	decreases activity, decreases expression	2
Diethylhexyl Phthalate	increases expression	2
Estrogens	affects metabolic processing, affects chemical synthesis	2
Mitotane	decreases reaction, increases expression, decreases expression	2
Fadrozole	decreases activity	2

ChEMBL screening assays

239 unique, capped per target: 198 binding, 37 admet, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002231	Binding	Inhibition of human recombinant CYP17 expressed in Escherichia coli at 2 uM	Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on potency and selectivity. — J Med Chem
CHEMBL4016915	ADMET	Inhibition of human CYP17A1 expressed in Escherichia coli membranes at 2 uM using [3H]-progesterone as substrate after 30 mins in presence of NADPH by HPLC analysis relative to control	Lead Optimization Generates CYP11B1 Inhibitors of Pyridylmethyl Isoxazole Type with Improved Pharmacological Profile for the Treatment of Cushing’s Disease. — J Med Chem
CHEMBL692481	Functional	In vitro inhibition of progesterone production in hamster ovarian tissue	Synthesis and aromatase inhibitory activity of novel 1-(4-aminophenyl)-3-azabicyclo[3.1.0]hexane- and -[3.1.1]heptane-2,4- diones. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03760835	PHASE4	RECRUITING	Congenital Adrenal Hyperplasia Once Daily Hydrocortisone Treatment
NCT04536662	PHASE4	UNKNOWN	Comparisons of Different Forms of Glucocorticoid on the Recovery of Reproductive Function in Patients With 21α-hydroxylase Deficiency
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00001521	PHASE3	COMPLETED	Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia
NCT02716818	PHASE3	COMPLETED	Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia
NCT03062280	PHASE3	COMPLETED	A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH
NCT03532022	PHASE3	WITHDRAWN	Open-label Comparison of Chronocort® Versus Standard Glucocorticoid Replacement Therapy
NCT04490915	PHASE3	ACTIVE_NOT_RECRUITING	Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia
NCT04806451	PHASE3	ACTIVE_NOT_RECRUITING	Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Participants With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study)
NCT05063994	PHASE3	COMPLETED	Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia
NCT05299554	PHASE3	COMPLETED	Long-term Safety Study of Chronocort in the Treatment of Participants With Congenital Adrenal Hyperplasia
NCT07144163	PHASE3	RECRUITING	A Study to Evaluate Atumelnant in Adults With Congenital Adrenal Hyperplasia
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00621985	PHASE2	COMPLETED	Dexamethasone Treatment of Congenital Adrenal Hyperplasia
NCT01735617	PHASE2	COMPLETED	Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH
NCT01771328	PHASE2	UNKNOWN	Continuous Subcutaneous Hydrocortisone Infusion in Congenital Adrenal Hyperplasia
NCT01859312	PHASE2	COMPLETED	Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia
NCT02804178	PHASE2	COMPLETED	A Study of ATR-101 for the Treatment of Congenital Adrenal Hyperplasia
NCT03257462	PHASE2	COMPLETED	Study of SPR001 in Adults With Classic Congenital Adrenal Hyperplasia
NCT03548246	PHASE2	WITHDRAWN	Androgen Reduction in Congenital Adrenal Hyperplasia
NCT03669549	PHASE2	TERMINATED	Nevanimibe HCl for the Treatment of Classic CAH
NCT03687242	PHASE2	COMPLETED	Study to Evaluate the Safety and Efficacy of SPR001 in Subjects With Classic Congenital Adrenal Hyperplasia
NCT04457336	PHASE2	TERMINATED	A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH
NCT04544410	PHASE2	TERMINATED	A Ph2b to Evaluate Tildacerfont in the Reduction of Glucocorticoid Steroid Doses in Adult CAH
NCT05128942	PHASE2	TERMINATED	A Phase 2 Study to Evaluate the Safety, Efficacy and PK of Tildacerfont in Children Aged 2-17 Years With CAH
NCT05907291	PHASE2	COMPLETED	Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 in Participants With Congenital Adrenal Hyperplasia (TouCAHn)
NCT06712823	PHASE2	RECRUITING	An Extension Study to Evaluate Safety and Efficacy in Participants Treated With CRN04894
NCT07187375	PHASE2	RECRUITING	Pharmacokinetics, Safety and Tolerability of Crinecerfont in Participants With Congenital Adrenal Hyperplasia Who Are Less Than 2 Years Old
NCT07536269	PHASE2	NOT_YET_RECRUITING	Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Crinecerfont in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Who Are Less Than 4 Years Old
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency