SRD5A1

Summary

SRD5A1 (steroid 5 alpha-reductase 1, HGNC:11284) is a protein-coding gene on chromosome 5p15.31, encoding 3-oxo-5-alpha-steroid 4-dehydrogenase 1 (P18405). Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids.

Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT). Also see SRD5A2 (MIM 607306).

Source: NCBI Gene 6715 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 46 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001047

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11284
Approved symbol	SRD5A1
Name	steroid 5 alpha-reductase 1
Location	5p15.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145545
Ensembl biotype	protein_coding
OMIM	184753
Entrez	6715

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 nonsense_mediated_decay

ENST00000274192, ENST00000504286, ENST00000510531, ENST00000513117, ENST00000854430, ENST00000854431, ENST00000854432

RefSeq mRNA: 3 — MANE Select: NM_001047 NM_001047, NM_001324322, NM_001324323

CCDS: CCDS3870

Canonical transcript exons

ENST00000274192 — 5 exons

Exon	Start	End
ENSE00000970925	6633440	6633869
ENSE00003466080	6662816	6662966
ENSE00003559472	6651842	6652008
ENSE00003630460	6656078	6656179
ENSE00003702040	6668202	6674386

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 97.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2327 / max 130.4980, expressed in 1797 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55634	8.8023	1760
55633	5.5482	1700
55635	0.6675	195
55636	0.2146	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	97.43	gold quality
upper leg skin	UBERON:0004262	97.19	gold quality
cervix squamous epithelium	UBERON:0006922	96.97	gold quality
squamous epithelium	UBERON:0006914	96.91	gold quality
endothelial cell	CL:0000115	96.89	gold quality
gingival epithelium	UBERON:0001949	96.54	gold quality
epithelium of esophagus	UBERON:0001976	96.29	gold quality
gingiva	UBERON:0001828	94.95	gold quality
mammalian vulva	UBERON:0000997	94.46	gold quality
cortical plate	UBERON:0005343	94.15	gold quality
hair follicle	UBERON:0002073	92.80	gold quality
tongue squamous epithelium	UBERON:0006919	92.71	gold quality
lower esophagus mucosa	UBERON:0035834	91.29	gold quality
esophagus mucosa	UBERON:0002469	90.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.92	gold quality
cervix epithelium	UBERON:0004801	90.68	gold quality
jejunal mucosa	UBERON:0000399	90.18	gold quality
upper arm skin	UBERON:0004263	89.52	gold quality
right lobe of liver	UBERON:0001114	89.45	gold quality
oral cavity	UBERON:0000167	88.95	gold quality
liver	UBERON:0002107	88.81	gold quality
skin of abdomen	UBERON:0001416	88.33	gold quality
skin of hip	UBERON:0001554	88.26	gold quality
zone of skin	UBERON:0000014	87.67	gold quality
oviduct epithelium	UBERON:0004804	87.47	gold quality
penis	UBERON:0000989	86.92	gold quality
monocyte	CL:0000576	86.81	gold quality
islet of Langerhans	UBERON:0000006	86.75	gold quality
nephron tubule	UBERON:0001231	86.62	gold quality
secondary oocyte	CL:0000655	86.53	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	11.87
E-ANND-3	yes	6.27
E-MTAB-5061	yes	5.69
E-MTAB-7008	no	83.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SIN3B

miRNA regulators (miRDB)

81 targeting SRD5A1, 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-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6512-3P	99.65	66.07	1468

Literature-anchored findings (GeneRIF, showing 40)

• role in blood pressure (PMID:11903314)
• examination of differential methylation of isoenzyme genes in lymphocytes (PMID:11948017)
• polymorphisms of SRD5A1 and SRD5A2 genes may not be directly associated with the development of baldness or generation of different clinical phenotypes. (PMID:12670724)
• Loss of 5alpha-reductase type I expression is associated with metastatic prostate cancer (PMID:12738739)
• Changes in 5alpha-reductase, 11beta-HSD1, and 20alpha/beta-HSD enzyme activities observed in polycystic ovary syndrome may contribute to increased production of cortisol and androgens. (PMID:14671189)
• Mutant SRD5A1 isoenzyme does not seem to play a crucial role in the development of hypospadias. (PMID:14739525)
• The direct challenge of beta-adrenergic agonists to glioma cells resulted in the rapid and transient elevation of 5alpha-R mRNA levels through the activation of the cyclic AMP (cAMP)/protein kinase A-mediated signaling pathway. (PMID:14997014)
• Glucocorticoids and androgens differentially regulate 5alphaR1 mRNA in the rat liver. Regulation of 5alphaR1 gene is primarily at the post-transcriptional level. (PMID:15004407)
• Candidate gene for benign prostatic hyperplasia. (PMID:15136785)
• Expression of SRD5A1 (5alphaR1) and SRD5A2 (5alphaR2) is elevated, and expression of AKR1C1 (20alpha-HSO), AKR1C2 (3alpha-HSO3) and AKR1C3 (3alpha-HSO2) is reduced in tumorous as compared to normal breast tissue. (PMID:15212687)
• 5alpha-reductase type 1 (5alphaR1) immunostaining is increased and 5alpha-reductase type 2(5alphaR2) immunostaining is decreased during development of prostate cancer and there is increased expression of both in recurrent and metastatic cancers (PMID:15538746)
• Serenoa repens inhibits this enzyme in the prostate, but does not suppress prostate-specific antigen secretion in prostate cancer. (PMID:15543614)
• 5alpha-reductase is expresed in human embryonic kidney cell line HEK293 (PMID:15792368)
• The expression of 5alpha-reductase type I mRNA was not regulated by calcitriol in a prostate tumor cell line. (PMID:15862960)
• SRD5A1 is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of SRD5A2-deficient males. (PMID:15941927)
• The SRD5A1 mRNA expression is 2-fold lower than SRD5A2 in normal rat. (PMID:16818707)
• These results suggest that intratumoral 5 alpha-dihydrotestosterone concentration is mainly determined by 5alphaRed1 and aromatase in breast carcinoma tissues. (PMID:17066438)
• Both 5-alpha-reductase I and II are expressed in normal human prostate stromal and epithelial cells. Only 5-alpha-reductase isoenzymes of prostate epithelium are modulated by oxytocin. (PMID:18008328)
• Hepatocyte growth factor stimulates 5alpha-R1 expression through up-regulation of the transcription factor early growth response 1 (PMID:18215136)
• Our results demonstrate that the 5alphaR activities of either bDPCs or sDPCs are stronger than that of dermal fibroblasts, despite the fact that the major steroidogenic activity is attributed to 17beta-HSD rather than 5alphaR among the three cell types. (PMID:18258185)
• Testosterone 5-alpha-Reductase deficiency is associated with gender identity (PMID:18422030)
• the SRD5A2 V89L VV genotype interacts with VDR FokI TT/CT genotypes in non-Hispanic White men and VDR CDX2 GG genotypes in Hispanic White men to increase the risk for prostate cancer. (PMID:18483391)
• Enhanced 5alphaR activity in both sexes is associated with insulin resistance but not body composition (PMID:18633104)
• A decreased local enzymatic conversion of testosterone may contribute to PAD genetic susceptibility. (PMID:19246976)
• Report changes in human placental 5alpha-reductase isoenzyme expression with advancing gestation: effects of fetal sex and glucocorticoid exposure. (PMID:19383266)
• hyperandrogenemia is associated with high levels of expression of 5-alpha reductase type 1 and, to a less extent, of type 2 isoenzyme in pubian skin cultured fibroblasts (PMID:19886072)
• We investigated associations between single nucleotide polymorphisms in genes HSD3B1, SRD5A1/2, and AKR1C2 and prostate cancer risk (PMID:20056642)
• Data indicate that enzymes CYP17A1 and HSD3B1 showed low expression, while AKR1C3 and SRD5A1 were abundantly expressed. (PMID:20086173)
• High nuclear SRD5A1 expression is associated with higher prostate cancer stage. (PMID:20519274)
• Evidence of association of two alleles for alcohol dependence (AD) is found in SRD5A1 and AKR1C3, mediating a protective effect of the minor allele at each AD marker based on the genotype of the second marker. (PMID:21323680)
• Pitfalls in the diagnosis of 5alpha-reductase type 2 deficiency during early infancy. (PMID:21447938)
• Single nucleotide polymorphisms in the two isoforms of 5alpha-reductase, SRD5A1 and SRD5A2, are associated with lean patients with polycystic ovary syndrome. (PMID:21530059)
• A statistically significant reduction of SRD5A1, SRD5A2, and CYP19A gene expression was found in the dermal papillae cells and peripheral blood mononuclear cells in idiopathic hirsutism. (PMID:21676395)
• Show positive associations of several SRD5A1 and SRD5A2 variations as independent predictors of biochemical recurrence after radical prostatectomy. (PMID:21715084)
• the dominant route of Dihydrotestosterone synthesis in castration-resistant prostate cancer bypasses testosterone, and instead requires 5alpha-reduction of androstenedione by SRD5A1 to 5alpha-androstanedione, which is then converted to DHT (PMID:21795608)
• Postmenopausal breast cancer risk associated with combined therapy may be modified by genetic variation in SRD5A1 (PMID:21947678)
• The different expression levels of 5alpha-reductase isoenzymes may confer response or resistance to 5alpha-reductase inhibitors. (PMID:22194926)
• Ten percent of cases and 44% of controls had the cytosine/cytosine (C/C) genotype for the SRD5A1 SNP, rs501999 indicating that this genotype may protect women against severe premenstrual symptoms. (PMID:22273344)
• Based on a limited selection of gene variants, no involvement of SRD5A1, SRD5A2, ESR1, ESR2 or PGR in female pattern hair loss is evident. (PMID:22509838)
• Different effects were seen for progesterone, which significantly decreased SRD5A1 protein levels. (PMID:23183084)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	srd5a1	ENSDARG00000020509
mus_musculus	Srd5a1	ENSMUSG00000021594
rattus_norvegicus	Srd5a1	ENSRNOG00000017601
caenorhabditis_elegans		WBGENE00008959
caenorhabditis_elegans		WBGENE00009635
caenorhabditis_elegans		WBGENE00014241

Paralogs (3): TECR (ENSG00000099797), TECRL (ENSG00000205678), SRD5A2 (ENSG00000277893)

Protein

Protein identifiers

3-oxo-5-alpha-steroid 4-dehydrogenase 1 — P18405 (reviewed: P18405)

Alternative names: SR type 1, Steroid 5-alpha-reductase 1

All UniProt accessions (4): A0AAA9YHF0, D6RDL6, P18405, D6RG03

UniProt curated annotations — full annotation on UniProt →

Function. Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.

Subcellular location. Microsome membrane. Endoplasmic reticulum membrane.

Tissue specificity. Liver and prostate (at a low level).

Induction. Its expression is regulated by androgens such as testosterone.

Similarity. Belongs to the steroid 5-alpha reductase family.

RefSeq proteins (3): NP_001038, NP_001311251, NP_001311252 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001104	3-oxo-5_a-steroid_4-DH_C	Domain
IPR016636	3-oxo-5-alpha-steroid_4-DH	Family
IPR039357	SRD5A/TECR	Family

Pfam: PF02544

Enzyme classification (BRENDA):

• EC 1.3.1.22 — 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) (BRENDA: 19 organisms, 63 substrates, 409 inhibitors, 93 Km, 0 kcat entries)
• EC 1.3.99.5 — 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) (BRENDA: 11 organisms, 23 substrates, 497 inhibitors, 9 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
TESTOSTERONE	—	36
NADPH	0.001–0.65	17
PROGESTERONE	0.0001–0.12	15
ANDROSTENEDIONE	0.0004–0.0263	7
CORTICOSTERONE	0.0006–0.018	5
20ALPHA-HYDROXYPROGESTERONE	0.0002–0.0005	3
(5ALPHA)-ANDROST-1-EN-3,17-DIONE	0.01–0.17	3
TESTOSTERONE	0.0004–0.01	3
17-EPITESTOSTERONE	0.0006–0.0008	2
17ALPHA-HYDROXYPROGESTERONE	0.0061–0.0088	2
20ALPHA-HYDROXYPREGN-4-EN-3-ONE	0.0009	1
3-KETO-DELTA4-ABIRATERONE	0.003	1
CORTISONE	0.14	1
DIHYDROTESTOSTERONE	0.0014	1
1-ANDROSTENE-3,17-DIONE	0.0066	1

Catalyzed reactions (Rhea), 4 shown:

• 5alpha-pregnane-3,20-dione + NADP(+) = progesterone + NADPH + H(+) (RHEA:21952)
• androst-4-ene-3,17-dione + NADPH + H(+) = 5alpha-androstan-3,17-dione + NADP(+) (RHEA:50816)
• 17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = testosterone + NADPH + H(+) (RHEA:50820)
• a 3-oxo-5alpha-steroid + NADP(+) = a 3-oxo-Delta(4)-steroid + NADPH + H(+) (RHEA:54384)

UniProt features (7 total): transmembrane region 5, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18405-F1	91.78	0.77

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-193048	Androgen biosynthesis
R-HSA-1430728	Metabolism
R-HSA-196071	Metabolism of steroid hormones
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 295 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_LIPID, JAEGER_METASTASIS_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_MALE_GENITALIA_DEVELOPMENT, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (42): urogenital system development (GO:0001655), liver development (GO:0001889), androgen biosynthetic process (GO:0006702), androgen catabolic process (GO:0006710), sex determination (GO:0007530), male gonad development (GO:0008584), cellular response to starvation (GO:0009267), response to xenobiotic stimulus (GO:0009410), response to muscle activity (GO:0014850), diterpenoid metabolic process (GO:0016101), spinal cord development (GO:0021510), hippocampus development (GO:0021766), thalamus development (GO:0021794), hypothalamus development (GO:0021854), pituitary gland development (GO:0021983), cerebral cortex development (GO:0021987), cell differentiation (GO:0030154), male genitalia development (GO:0030539), female genitalia development (GO:0030540), response to follicle-stimulating hormone (GO:0032354), cellular response to insulin stimulus (GO:0032869), serotonin metabolic process (GO:0042428), progesterone metabolic process (GO:0042448), response to estrogen (GO:0043627), bone development (GO:0060348), response to growth hormone (GO:0060416), response to fungicide (GO:0060992), cellular response to cAMP (GO:0071320), cellular response to growth factor stimulus (GO:0071363), cellular response to estradiol stimulus (GO:0071392), cellular response to testosterone stimulus (GO:0071394), cellular response to dexamethasone stimulus (GO:0071549), cellular response to epinephrine stimulus (GO:0071872), cellular response to serotonin (GO:1904015), response to resveratrol (GO:1904638), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), sex differentiation (GO:0007548), steroid metabolic process (GO:0008202), androgen metabolic process (GO:0008209)

GO Molecular Function (8): 3-oxo-5-alpha-steroid 4-dehydrogenase activity (GO:0003865), electron transfer activity (GO:0009055), obsolete amide binding (GO:0033218), 3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity (GO:0047751), NADPH binding (GO:0070402), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), cell body fiber (GO:0070852), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of steroid hormones	1
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	5
diencephalon development	3
gland development	2
androgen metabolic process	2
pallium development	2
limbic system development	2
genitalia development	2
cytoplasm	2
cellular anatomical structure	2
system development	1
renal system development	1
hepaticobiliary system development	1
hormone biosynthetic process	1
steroid hormone biosynthetic process	1
steroid catabolic process	1
hormone catabolic process	1
developmental process involved in reproduction	1
gonad development	1
development of primary male sexual characteristics	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
response to chemical	1
response to activity	1
terpenoid metabolic process	1
central nervous system development	1
endocrine system development	1
cellular developmental process	1
male sex differentiation	1
reproductive system development	1
female sex differentiation	1
response to gonadotropin	1
steroid dehydrogenase activity, acting on the CH-CH group of donors	1
molecular_function	1
3-oxo-5-alpha-steroid 4-dehydrogenase activity	1
enone reductase activity	1
anion binding	1
NADP binding	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRD5A1	SRD5A3	Q9H8P0	967
SRD5A1	CYP17A1	P05093	929
SRD5A1	AKR1D1	P51857	888
SRD5A1	AKR1C3	P42330	863
SRD5A1	TECRL	Q5HYJ1	834
SRD5A1	HSD11B1	P28845	820
SRD5A1	HSD3B2	P26439	816
SRD5A1	HSD11B2	P80365	800
SRD5A1	HSD17B3	P37058	792
SRD5A1	CYP11A1	P05108	785
SRD5A1	AKR1C2	P52895	779
SRD5A1	HSD17B2	P37059	775
SRD5A1	HSD17B6	O14756	770
SRD5A1	AKR1C1	P52896	759
SRD5A1	SULT2A1	Q06520	749

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SRD5A1	ACTBL2	psi-mi:“MI:0915”(physical association)	0.590
SRD5A1	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (6): ACTBL2 (Affinity Capture-MS), SRD5A1 (Affinity Capture-RNA), SRD5A1 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), SRD5A1 (Affinity Capture-RNA), SRD5A1 (Affinity Capture-RNA)

ESM2 similar proteins: A2XWN6, B4FHU1, B8B6G5, C7T2J9, F4J4C8, O08984, O12947, O18765, O70536, O77760, O77761, P18405, P23913, P24008, P31213, P31214, P35610, Q0P4J9, Q0WVZ1, Q14739, Q17428, Q28891, Q28892, Q5R7H4, Q5RIU9, Q60457, Q61263, Q651J5, Q657S5, Q6K991, Q7F0Q2, Q7XUH5, Q84N34, Q8AVI9, Q8BFZ1, Q8GW19, Q8L718, Q8L7R3, Q8S403, Q93YU2

Diamond homologs: A2XWN6, A5PJS2, A8X8R3, B8B6G5, C7T2J9, D2HBV9, I1HTF7, O18765, O94511, P18405, P24008, P31213, P31214, Q17428, Q28891, Q28892, Q2QDF6, Q38944, Q55C17, Q5K2N1, Q5RJM1, Q68FF9, Q7F0Q2, Q7XUH5, Q99N99, Q9CAH5, Q9H8P0, Q9N5Y2, Q9SI62, Q9UT20, Q9WUP4, Q9M2U2, Q9VLP9, P40526, Q0P4J9, Q5RIU9, Q8AVI9, Q3SZ89, Q3ZCD7, Q57ZC7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
testosterone	“up-regulates activity”	SRD5A1	“chemical activation”
SRD5A1	“up-regulates quantity”	17beta-hydroxy-5alpha-androstan-3-one	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

872 predictions. Top by Δscore:

Variant	Effect	Δscore
5:6656177:GGG:G	donor_gain	1.0000
5:6656178:GGG:G	donor_gain	1.0000
5:6662965:GA:G	donor_gain	1.0000
5:6662967:G:GG	donor_gain	1.0000
5:6656176:AGGG:A	donor_gain	0.9900
5:6656177:GGGG:G	donor_gain	0.9900
5:6662810:TTCTA:T	acceptor_loss	0.9900
5:6662811:TCTAG:T	acceptor_loss	0.9900
5:6662812:CTA:C	acceptor_loss	0.9900
5:6662813:TA:T	acceptor_loss	0.9900
5:6662814:A:AC	acceptor_loss	0.9900
5:6662815:GGA:G	acceptor_gain	0.9900
5:6662947:AG:A	donor_gain	0.9900
5:6662962:CATGA:C	donor_gain	0.9900
5:6662964:TGA:T	donor_gain	0.9900
5:6662965:GAG:G	donor_gain	0.9900
5:6668336:A:AG	donor_gain	0.9900
5:6651840:A:G	acceptor_gain	0.9800
5:6656176:AGGGG:A	donor_loss	0.9800
5:6656180:GTAC:G	donor_loss	0.9800
5:6656181:T:TG	donor_loss	0.9800
5:6656182:A:AG	donor_loss	0.9800
5:6662813:TAGG:T	acceptor_gain	0.9800
5:6662814:A:AG	acceptor_gain	0.9800
5:6662814:AGGA:A	acceptor_gain	0.9800
5:6662815:G:GG	acceptor_gain	0.9800
5:6662815:GGAG:G	acceptor_gain	0.9800
5:6662946:T:TA	donor_gain	0.9800
5:6662963:ATGA:A	donor_gain	0.9800
5:6662964:TGAGT:T	donor_loss	0.9800

AlphaMissense

1677 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:6668218:T:C	F244L	0.994
5:6668220:T:A	F244L	0.994
5:6668220:T:G	F244L	0.994
5:6662824:T:C	F191L	0.993
5:6662826:T:A	F191L	0.993
5:6662826:T:G	F191L	0.993
5:6662914:T:C	F221L	0.991
5:6662916:T:A	F221L	0.991
5:6662916:T:G	F221L	0.991
5:6651915:T:C	F123L	0.988
5:6651917:C:A	F123L	0.988
5:6651917:C:G	F123L	0.988
5:6633847:T:C	F91L	0.987
5:6633849:C:A	F91L	0.987
5:6633849:C:G	F91L	0.987
5:6651942:A:C	S132R	0.987
5:6651944:C:A	S132R	0.987
5:6651944:C:G	S132R	0.987
5:6662869:T:A	W206R	0.987
5:6662869:T:C	W206R	0.987
5:6662824:T:A	F191I	0.986
5:6656123:A:T	D169V	0.985
5:6656145:A:C	R176S	0.985
5:6656145:A:T	R176S	0.985
5:6662858:A:T	E202V	0.985
5:6656089:T:A	W158R	0.984
5:6656089:T:C	W158R	0.984
5:6656123:A:C	D169A	0.984
5:6651920:T:G	C124W	0.983
5:6662847:C:A	N198K	0.983

dbSNP variants (sampled 300 via entrez): RS1000067194 (5:6641287 C>A), RS1000077460 (5:6637938 A>G), RS1000083418 (5:6647381 A>C), RS1000089723 (5:6652484 T>C), RS1000117715 (5:6633562 T>C), RS1000205148 (5:6643645 C>T), RS1000255709 (5:6643999 A>G), RS1000337337 (5:6666588 C>T), RS1000340006 (5:6641452 A>G), RS1000388984 (5:6632925 C>T), RS1000448909 (5:6636708 A>G), RS1000560328 (5:6667752 A>G), RS1000614676 (5:6662147 C>A), RS1000674870 (5:6667471 G>A,T), RS1000850972 (5:6673614 A>C,G)

Disease associations

OMIM: gene MIM:184753 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001525_8	Visceral fat	3.000000e-06
GCST001651_47	Response to amphetamines	3.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1787 (SINGLE PROTEIN), CHEMBL2363075 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 73,159 (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
CHEMBL1200969	DUTASTERIDE	4	11,156
CHEMBL710	FINASTERIDE	4	51,247
CHEMBL138225	EPRISTERIDE	2	10,015
CHEMBL24955	BEXLOSTERIDE	2	741

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

Binding affinities (BindingDB)

8 measured of 20 human assays (20 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(1S,9aR,11aS)-6,9a,11a-Trimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-1-ylamide	KI	1.1 nM
(1S,9aR,11aS)-6-Bromo-9a,11a-dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-1-ylamide	KI	4.5 nM
(1S,9aR,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-2-yl ester	KI	6.9 nM
1-(Adamantane-2-carbonyl)-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-cyclopenta[i]phenanthridin-7-one	KI	6.9 nM
(1S,9aR,11aS)-5,9a,11a-Trimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-1-ylamide	KI	8.5 nM
(1S,9aR,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-1-ylamide	KI	11 nM
(1S,9aR,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,9a,9b,10,11,11a-dodecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-1-ylamide	KI	74 nM
17-Chloro-16-formylandros-5,16-diene-3β-yl-p-bromobenzoate (10)	IC50	800 nM

ChEMBL bioactivities

574 potent at pChembl≥5 of 580 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.89	Ki	0.13	nM	CHEMBL86832
9.70	Ki	0.2	nM	CHEMBL25183
9.70	Ki	0.2	nM	CHEMBL282037
9.70	Ki	0.2	nM	CHEMBL2115222
9.70	Ki	0.2	nM	CHEMBL445627
9.52	Ki	0.3	nM	CHEMBL283123
9.40	Ki	0.4	nM	CHEMBL1159458
9.30	IC50	0.5	nM	CHEMBL25448
9.30	Ki	0.5	nM	CHEMBL421735
9.22	Ki	0.6	nM	CHEMBL283430
9.22	Ki	0.6	nM	CHEMBL2115222
9.22	IC50	0.6	nM	CHEMBL421627
9.05	IC50	0.9	nM	CHEMBL25448
9.05	IC50	0.9	nM	CHEMBL420415
9.04	IC50	0.91	nM	CHEMBL275153
9.00	Ki	1	nM	CHEMBL307745
8.96	Ki	1.1	nM	CHEMBL306289
8.89	Ki	1.3	nM	CHEMBL87805
8.82	Ki	1.5	nM	CHEMBL88032
8.80	IC50	1.6	nM	CHEMBL126686
8.77	IC50	1.7	nM	CHEMBL2298601
8.77	IC50	1.7	nM	CHEMBL24193
8.77	IC50	1.7	nM	CHEMBL340027
8.75	IC50	1.77	nM	CHEMBL280015
8.70	IC50	2	nM	CHEMBL128023
8.68	IC50	2.11	nM	CHEMBL17245
8.66	IC50	2.19	nM	CHEMBL17222
8.64	IC50	2.3	nM	BEXLOSTERIDE
8.63	IC50	2.35	nM	CHEMBL16863
8.62	IC50	2.42	nM	CHEMBL274269
8.62	IC50	2.4	nM	CHEMBL283245
8.60	IC50	2.5	nM	CHEMBL338376
8.59	IC50	2.6	nM	CHEMBL340715
8.59	IC50	2.6	nM	CHEMBL340181
8.57	Ki	2.7	nM	CHEMBL118446
8.57	IC50	2.7	nM	CHEMBL340684
8.53	IC50	2.93	nM	CHEMBL276320
8.52	IC50	3.05	nM	CHEMBL277053
8.52	IC50	3	nM	CHEMBL25083
8.52	Ki	3	nM	CHEMBL314309
8.52	Ki	3	nM	CHEMBL2298601
8.51	Ki	3.1	nM	CHEMBL90440
8.51	Ki	3.1	nM	CHEMBL80160
8.49	IC50	3.22	nM	CHEMBL16784
8.49	Ki	3.2	nM	CHEMBL311045
8.48	IC50	3.31	nM	CHEMBL278490
8.48	IC50	3.3	nM	CHEMBL24958
8.48	IC50	3.3	nM	CHEMBL340305
8.47	IC50	3.4	nM	CHEMBL130845
8.47	Ki	3.4	nM	CHEMBL328670

PubChem BioAssay actives

523 with measured affinity, of 708 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
(1S,9aR,11aS)-N-[2-chloro-6-(trifluoromethyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207585: Binding affinity to recombinant human Steroid 5-alpha-reductase type I was evaluated	ki	0.0001	uM
(1S,9aR,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-6-chloro-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207919: Binding affinity for human 5 alpha reductase 1 isozyme	ki	0.0002	uM
(1S,9aR,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207919: Binding affinity for human 5 alpha reductase 1 isozyme	ki	0.0002	uM
(1S,9aR,11aS)-N-[2,6-bis(trifluoromethyl)phenyl]-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0002	uM
(1S,3aS,3bS,9aR,9bS,11aS)-N-[2,6-bis(trifluoromethyl)phenyl]-6-chloro-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0002	uM
(1S,9aR,11aS)-N-(4-chlorophenyl)-N-cyclopentyl-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0003	uM
1-[4-[(2R,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3,4,5,6-tetramethyl-3-[(2S,3R,4S,5R)-3,4,5-trihydroxy-2,4,5,6,6-pentamethyloxan-2-yl]oxyoxan-2-yl]oxy-2,6-dihydroxyphenyl]-3-(3-hydroxy-4-methoxyphenyl)propan-1-one	207920: In vitro inhibitory activity against human type 1 5-alpha reductase	ki	0.0004	uM
(1R,4S,9aR,11aR)-4,6,9a,11a-tetramethyl-1-(6-methylheptan-2-yl)-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-7-one	207757: Inhibition of human Steroid 5-alpha-reductase type I	ic50	0.0005	uM
(1S,9aR,11aS)-N-[2-tert-butyl-6-(trifluoromethyl)phenyl]-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0005	uM
(1S,9aR,11aS)-6-chloro-N-(4-chlorophenyl)-N-cyclopentyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0006	uM
(4R,9aR,11aR)-4,6,9a,11a-tetramethyl-1-(6-methylheptan-2-yl)-2,3,3a,3b,4,8,9,9b,10,11-decahydro-1H-indeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0006	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-pentylformamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0009	uM
(1S,9aR,11aS)-N-[1-(4-chlorophenyl)cyclopentyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207458: Inhibition of recombinant Steroid 5-alpha-reductase type I was evaluated as binding affinity of the compound	ic50	0.0009	uM
(1S,9aR,11aS)-9a,11a-dimethyl-1-nonanoyl-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridin-7-one	207920: In vitro inhibitory activity against human type 1 5-alpha reductase	ki	0.0010	uM
(1S,9aR,11aS)-N-(1-adamantyl)-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207920: In vitro inhibitory activity against human type 1 5-alpha reductase	ki	0.0011	uM
(1S,9aR,11aS)-N-[2-tert-butyl-5-(4-tert-butylphenyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0013	uM
(1S,9aR,11aS)-N-[1-(4-tert-butylphenyl)cyclohexyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0015	uM
(4S,9aR,11aR)-4,9a,11a-trimethyl-1-(6-methylheptan-2-yl)-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0016	uM
(1R,9aR,11aR)-6,9a,11a-trimethyl-1-(6-methylheptan-2-yl)-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-7-one	207917: Inhibitory concentration was tested on human 5-alpha reductase 1 isozyme	ic50	0.0017	uM
(9aR,11aR)-6,9a,11a-trimethyl-1-(6-methylheptan-2-yl)-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0017	uM
(1S,3aS,3bS,5aR,9aR,9bS,11aS)-N,N-diethyl-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinoline-1-carboxamide	207917: Inhibitory concentration was tested on human 5-alpha reductase 1 isozyme	ic50	0.0017	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-pentylpentanamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0018	uM
(4S,9aR,11aR)-4,6,9a,11a-tetramethyl-1-(6-methylheptan-2-yl)-2,3,3a,3b,4,5,5a,9b,10,11-decahydro-1H-indeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0020	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-(4-methoxyphenyl)benzamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0021	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-(3-methylbutyl)formamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0022	uM
(4aR,10bR)-8-chloro-4-methyl-1,2,4a,5,6,10b-hexahydrobenzo[f]quinolin-3-one	207762: Inhibitory activity against Steroid 5-alpha-reductase type I in human scalp homogenates	ic50	0.0023	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-5-bromo-N-pentylpentanamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0024	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-(3,3-dimethylbutyl)formamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0024	uM
(1S,9aR,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207917: Inhibitory concentration was tested on human 5-alpha reductase 1 isozyme	ic50	0.0024	uM
(4R,9aR,11aR)-4,9a,11a-trimethyl-1-(6-methylheptan-2-yl)-1,2,3,3a,3b,4,6,8,9,9b,10,11-dodecahydroindeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0025	uM
(9aR,11aR)-9a,11a-dimethyl-1-(6-methylheptan-2-yl)-1,2,3,3a,3b,4,5,5a,6,8,9,9b,10,11-tetradecahydroindeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0026	uM
(4S,9aR,11aR)-4,9a,11a-trimethyl-1-(6-methylheptan-2-yl)-1,2,3,3a,3b,4,5,5a,6,8,9,9b,10,11-tetradecahydroindeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0026	uM
8-chloro-4-methyl-1,2,5,6-tetrahydrobenzo[f]quinolizin-3-one	207886: Inhibition constant against recombinant Steroid 5-alpha-reductase type I expressed in CHO cells	ki	0.0027	uM
(4S,9aR,11aR)-4-ethyl-9a,11a-dimethyl-1-(6-methylheptan-2-yl)-1,2,3,3a,3b,4,5,5a,6,8,9,9b,10,11-tetradecahydroindeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0027	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-phenylbenzamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0029	uM
4-[3-[3-[bis[4-(2-methylpropyl)phenyl]methylamino]benzoyl]indol-1-yl]butanoic acid	207598: In vitro inhibitory activity against human Steroid 5-alpha-reductase type 1 in COS-1 cells was determined	ic50	0.0030	uM
(1S,9aR,11aS)-N-[1-(4-tert-butylphenyl)cyclopentyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0030	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-butylformamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0031	uM
(1S,9aR,11aS)-5,9a,11a-trimethyl-1-(3-methylbutanoyl)-2,3,3a,3b,4,8,9,9b,10,11-decahydro-1H-cyclopenta[i]phenanthridin-7-one	207920: In vitro inhibitory activity against human type 1 5-alpha reductase	ki	0.0031	uM
(1S,9aR,11aS)-N-[1-(4-chlorophenyl)cyclohexyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0031	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-pentylbenzamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0032	uM
(1S,9aR,11aS)-6-bromo-9a,11a-dimethyl-1-(3-methylbutanoyl)-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridin-7-one	207920: In vitro inhibitory activity against human type 1 5-alpha reductase	ki	0.0032	uM
N-[(1S,5aR,9aR,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-pentylbutanamide	207456: In vitro inhibition of human steroid 5-alpha-reductase type I in Du-145 cells	ic50	0.0033	uM
(1R,4S,9aR,11aR)-6-ethyl-4,9a,11a-trimethyl-1-(6-methylheptan-2-yl)-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-7-one	207917: Inhibitory concentration was tested on human 5-alpha reductase 1 isozyme	ic50	0.0033	uM
(4S,9aR,11aR)-6-ethyl-4,9a,11a-trimethyl-1-(6-methylheptan-2-yl)-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-7-one	207913: Inhibition of type 1 steroid-5-alpha-reductase	ic50	0.0033	uM
(4aR,10bR)-4,10b-dimethyl-8-[(E)-2-quinolin-3-ylethenyl]-2,4a,5,6-tetrahydro-1H-benzo[f]quinolin-3-one	207600: Inhibitory activity against Steroid 5-alpha-reductase type 1 enzyme based on the conversion of [3H]T to [3H]-DHT in nuclear membrane preparations from human scalp	ic50	0.0034	uM
(1S,9aR,11aS)-N-[2-tert-butyl-5-(4-chlorophenyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0034	uM
(1S,9aR,11aS)-N-benzhydryl-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207920: In vitro inhibitory activity against human type 1 5-alpha reductase	ki	0.0036	uM
(1S,9aR,11aS)-N-[1-(4-tert-butylphenyl)cycloheptyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207586: Inhibition of recombinant steroid 5-alpha-reductase type I	ki	0.0036	uM
(1S,3aS,3bS,5aR,9aR,9bS,11aS)-N-(1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-yl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	1573006: Inhibition of human type 1 5alpha reductase	ic50	0.0039	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Dihydrotestosterone	affects reaction, decreases reaction, increases expression, increases abundance, increases metabolic processing	4
Testosterone	increases abundance, increases metabolic processing, increases reaction, affects cotreatment, increases expression (+1 more)	4
tributyltin	affects cotreatment, increases expression, decreases activity	3
Finasteride	decreases activity, affects cotreatment, increases expression	3
2,3-dibromopropyl-2,4,6-tribromophenyl ether	decreases expression	2
Doxorubicin	increases expression, affects response to substance	2
Progesterone	decreases expression, increases metabolic processing, increases chemical synthesis, increases reduction	2
5-alpha-Dihydroprogesterone	increases chemical synthesis, increases metabolic processing	2
allyl 2,4,6-tribromophenyl ether	decreases expression	1
perfluorotetradecanoic acid	decreases activity	1
perfluorotridecanoic acid	decreases activity	1
lauryl gallate	decreases reaction, increases abundance, increases metabolic processing, decreases activity	1
hydroxyflutamide	decreases expression	1
beta-lapachone	decreases expression	1
n-butyl gallate	decreases reaction, increases abundance, increases metabolic processing, decreases activity	1
afimoxifene	increases expression	1
octyl gallate	decreases activity	1
vinyl fluoride	decreases activity	1
allopregnane-3,20-diol	increases chemical synthesis	1
dibutyldichlorotin	decreases activity	1
vinclozolin	affects reaction, decreases reaction, increases expression	1
bromotriethylstannane	decreases activity	1
periodate-oxidized adenosine	affects expression	1
allopregnan-20 alpha-ol-3-one	increases chemical synthesis	1
triphenyltin	decreases activity, decreases reaction	1
17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one	decreases activity	1
piperidine	decreases activity	1
perfluorodecanoic acid	decreases activity	1
beta-methylcholine	affects expression	1
ethyl gallate	decreases activity	1

ChEMBL screening assays

104 unique, capped per target: 100 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1106728	Binding	Inhibition of human 5alpha reductase 1 expressed in HEK293 cells assessed as inhibition of conversion of [14C]4-androstene-3,17-dione to [14C]5R-androstane-3,17-dione at 0.3 uM after 1 hr	Potent and selective steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 7, an enzyme that catalyzes the reduction of the key hormones estrone and dihydrotestosterone. — J Med Chem
CHEMBL829929	Functional	Inhibition of [1-beta-3H]-androstenedione binding to human steroid 5-alpha-reductase type I expressed in DU-145 cells at 10 uM	Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HB	Abcam HeLa SRD5A1 KO	Cancer cell line	Female
CVCL_TQ39	HAP1 SRD5A1 (-) 1	Cancer cell line	Male
CVCL_TQ40	HAP1 SRD5A1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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