{"entity":{"id":"akr1c3","kind":"target","name":"AKR1C3","aka":["aldo-keto reductase family 1 member C3","HSD17B5"],"tldr":"AKR1C3 is an enzyme that makes potent male hormones and that some cancers carry in large amounts. Rather than blocking it, prodrugs use it as a key: they stay inactive until AKR1C3 inside a tumour cell converts them into a DNA-damaging drug.","summary":"AKR1C3 (chromosome 10p15.1) is a cytosolic aldo-keto reductase that reduces ketosteroids, producing potent androgens such as testosterone (UniProt P42330). A 2019 Clinical Cancer Research study described OBI-3424 as a highly selective prodrug that AKR1C3 converts to a potent DNA-alkylating agent, found AKR1C3 expression much higher in T-lineage than B-lineage acute lymphoblastic leukaemia, and reported prolonged event-free survival in all nine leukaemia xenografts tested (Evans et al., doi:10.1158/1078-0432.CCR-19-0551). In OnCo, AST-3424 (OBI-3424) and AST-001 come from Ascentawits' AKR1C3-activated prodrug platform, designed to kill tumour cells that overexpress the enzyme.","asOf":"2026-11-03","links":[{"label":"HGNC HGNC:386","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:386"},{"label":"UniProt P42330","url":"https://www.uniprot.org/uniprotkb/P42330/entry"},{"label":"NCBI Gene 8644","url":"https://www.ncbi.nlm.nih.gov/gene/8644"},{"label":"OBI-3424, a novel AKR1C3-activated prodrug, in preclinical models of T-ALL (Clin Cancer Res 2019)","url":"https://doi.org/10.1158/1078-0432.CCR-19-0551"}],"tags":["pipeline-gap-target"],"related":[],"cancers":["all-leukemia","hcc","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["ast-001","ast-3424"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded: HGNC, UniProt and the paper cited give no positivity rate."],"provenance":{"editedBy":"OnCo gap audit, class 5 targets (HGNC REST, UniProt REST, Europe PMC, corpus drug records)","editedOn":"2026-11-03"},"symbol":"AKR1C3","role":["drug-target"],"sources":[],"specificitySources":[],"hgnc":"HGNC:386","ensembl":"ENSG00000196139","uniprot":"P42330","entrez":"8644","biology":"NADPH-dependent reductase with broad ketosteroid substrate specificity (UniProt P42330); in these medicines it is the activating enzyme, not the thing inhibited.","whereFound":["T-lineage acute lymphoblastic leukaemia (higher expression, doi:10.1158/1078-0432.CCR-19-0551)","Hepatocellular carcinoma and pancreatic cancer (AST-3424 and AST-001 trials)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/akr1c3/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"ast-001","kind":"drug","name":"AST-001","route":"/drugs/ast-001/"},{"id":"ast-3424","kind":"drug","name":"AST-3424","route":"/drugs/ast-3424/"}]}}