# DHODH

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

## TL;DR

DHODH is an enzyme cells need to make pyrimidines, the building blocks of DNA and RNA. Blocking it pushed immature leukaemia cells to mature in mouse studies, and a DHODH inhibitor is in an early trial in solid tumours and lymphoma.

## Summary

DHODH (chromosome 16q22.2) converts dihydroorotate to orotate, a step required for the cell's own (de novo) synthesis of UMP and so of pyrimidine nucleotides (UniProt Q02127). A 2016 Cell study screening for compounds that overcome the differentiation block of acute myeloid leukaemia found that inhibiting DHODH let leukaemia cells mature in human and mouse models, and that DHODH inhibitors reduced leukaemic burden and leukaemia-initiating cells and improved survival in mice (Sykes et al., doi:10.1016/j.cell.2016.08.057). In OnCo, JBZ-001 is an oral DHODH inhibitor in a phase 1 trial in advanced solid tumours and non-Hodgkin lymphoma.

## Fields

- Kind: Target
- Last checked: 2026-11-03
- Also known as: dihydroorotate dehydrogenase
- Tags: pipeline-gap-target
- Symbol: DHODH
- Class: enzyme
- Biology: Enzyme that uses a quinone as electron acceptor to make orotate, required for UMP biosynthesis by the de novo pathway (UniProt Q02127).
- Where found: Acute myeloid leukaemia in preclinical models (doi:10.1016/j.cell.2016.08.057); Advanced solid tumours and non-Hodgkin lymphoma (JBZ-001 trial)

## Notes

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

## Sources

- HGNC HGNC:2867: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2867
- UniProt Q02127: https://www.uniprot.org/uniprotkb/Q02127/entry
- NCBI Gene 1723: https://www.ncbi.nlm.nih.gov/gene/1723
- Inhibition of dihydroorotate dehydrogenase overcomes differentiation blockade in AML (Cell 2016): https://doi.org/10.1016/j.cell.2016.08.057

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- drugs: [JBZ-001](https://onco.cc/drugs/jbz-001/)

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JSON: https://onco.cc/api/v1/entities/dhodh.json