OncoSignal
Live from Open Targets Platform, fetched 2026-11-11 16:35 UTC. Every row links to its source record.

AKR1C3 aldo-keto reductase family 1 member C3

ENSG00000196139 · protein coding · Open Targets profile

Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids. Displays broad substrate specificity with distinct positional and stereochemistry, primarily generating 17beta-hydroxysteroids, but also 3alpha- and 20alpha- hydroxysteroids (PubMed:10998348, PubMed:11165022, PubMed:20036328, PubMed:9415401, PubMed:9927279, PubMed:10998348, PubMed:9927279). Produces potent androgens via classical and 'backdoor'/alternative pathways. In the classical androgen metabolic pathway (biosynthesis of 5alpha-dihydrotestosterone (5alpha-DHT) via testosterone), catalyzes the reduction of delta4-androstenedione to form testosterone (PubMed:10998348, PubMed:11165022, PubMed:20036328, PubMed:9415401, PubMed:9927279). In the 'backdoor' androgen metabolic pathway (biosynthesis of 5alpha-dihydrotestosterone (5alpha-DHT) via pregnanes), reduces androsterone to 5alpha-androstane-3alpha,17beta- diol preceding 5alpha-DHT secretion (PubMed:10557352, PubMed:10998348, PubMed:9415401). Reduces 5alpha-DHT to less potent androgen 5alpha- androstane-3alpha,17beta-diol, likely regulating ligand availability for androgen receptors (PubMed:10557352, PubMed:10998348, PubMed:11165022, PubMed:14672942, PubMed:7650035, PubMed:9415401). May contribute to the metabolism of adrenal-derived androgen precursors. Reduces 11-keto-4-androstene-3,17-dione (11KA4) and 11-keto-5alpha- androstane-3,17-dione (11K-Adione) into potent androgens 11- ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT), respectively (PubMed:31926269). In estrogen metabolism, catalyzes the conversion of estrone to potent estrogen 17beta-estradiol (PubMed:10998348, PubMed:11165022, PubMed:20036328). Acts as a prostaglandin (PG) F2alpha synthase. Displays 11-ketoreductase and 9,11-endoperoxide reductase activities and reduces PGD2 to 11beta- PGF2alpha and PGH2 to PGF2alpha (PubMed:10622721, PubMed:11165022, PubMed:15047184, PubMed:19010934, PubMed:20036328, PubMed:7650035, PubMed:9415401, PubMed:9927279). Also displays retinaldehyde reductase activity toward 9-cis-retinal (PubMed:21851338). In vitro can efficiently catalyze bidirectional conversion between ketosteroids and hydroxysteroids using NADPH/NADP(+) or NADH/NAD(+) as cofactors. In vivo however, the reductase activity prevails since the major reducing cofactor NADPH inhibits NAD(+)-dependent oxidase activity (PubMed:11165022, PubMed:14672942). In addition, it is able to reduce in vitro various carbonyl compounds like menadione, phenanthrenequinone and nitrobenzaldehyde (By similarity). {ECO:0000250|UniProtKB:P05980, ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:15047184, ECO:0000269|PubMed:19010934, ECO:0000269|PubMed:20036328, ECO:0000269|PubMed:21851338, ECO:0000269|PubMed:31926269, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}.

In 2 of 15 cancers, the evidence for AKR1C3 comes mainly from mutations found in tumours

Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.

Inherited (germline) variantsMutations in tumours (somatic)
00.250.50.751prostate cancerprostate cancerprostate cancer: somatic 0.18Familial prostate cancerFamilial prostate cancerFamilial prostate cancer: somatic 0.18hepatocellular carcinomahepatocellular carcinomaesophageal adenocarcinomaesophageal adenocarcinomagastric cancergastric cancerliver cancerliver cancersmall cell lung carcinomasmall cell lung carcinomaprostate carcinomaprostate carcinomaacute lymphoblastic leukemiaacute lymphoblastic leukemiaplacental site trophoblastic tumorplacental site trophoblastic tumorinvasive hydatidiform moleinvasive hydatidiform molebreast carcinomabreast carcinomabreast cancerbreast cancernon-small cell lung carcinomanon-small cell lung carcinomacolorectal carcinomacolorectal carcinoma

Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.

Tractability

Small molecule
Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
PROTAC
Database Ubiquitination, Half-life Data, Small Molecule Binder

gnomAD loss of function constraint: o/e 1.0999000072479248 (upper bound 1.3990000486373901). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.

Who runs trials of these drugs

No named investigators on registry trials of AKR1C3's approved or late-stage drugs in the last three years.

No terminated, withdrawn or suspended trials of AKR1C3's drugs are registered

All 0 drugs and clinical candidates as a table

Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.

DrugTypeHighest stageIndicationsSource records
No drugs or clinical candidates recorded.