# AKR1C3

Source: https://onco.cc/targets/akr1c3/  
OnCo record `akr1c3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Target
- Last checked: 2026-11-03
- Also known as: aldo-keto reductase family 1 member C3; HSD17B5
- Tags: pipeline-gap-target
- Symbol: AKR1C3
- Class: enzyme
- Biology: NADPH-dependent reductase with broad ketosteroid substrate specificity (UniProt P42330); in these medicines it is the activating enzyme, not the thing inhibited.
- Where found: 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)

## Notes

- Prevalence not recorded: HGNC, UniProt and the paper cited give no positivity rate.

## Sources

- HGNC HGNC:386: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:386
- UniProt P42330: https://www.uniprot.org/uniprotkb/P42330/entry
- NCBI Gene 8644: https://www.ncbi.nlm.nih.gov/gene/8644
- OBI-3424, a novel AKR1C3-activated prodrug, in preclinical models of T-ALL (Clin Cancer Res 2019): https://doi.org/10.1158/1078-0432.CCR-19-0551

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- drugs: [AST-001](https://onco.cc/drugs/ast-001/), [AST-3424](https://onco.cc/drugs/ast-3424/)

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