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The enzyme that makes DNA building blocks from RNA building blocks. Gemcitabine's active form shuts it down and hydroxyurea quenches its catalytic radical, starving dividing cells of the nucleotides they need.
Ribonucleotide reductase converts ribonucleoside diphosphates into the deoxyribonucleotides used to make DNA, the rate-limiting step of DNA precursor supply. Gemcitabine diphosphate inhibits the RRM1 large subunit while gemcitabine triphosphate is built into DNA and stops chain extension, a self-potentiating combination that underlies its use in pancreatic, lung, bladder, ovarian and breast cancers. Hydroxyurea scavenges the tyrosyl radical of the small subunit and is used to control blood counts in myeloproliferative neoplasms and chronic myeloid leukaemia. High RRM1 expression is associated with gemcitabine resistance.
In plain words · The enzyme that makes DNA building blocks from RNA building blocks. Gemcitabine's active form shuts it down and hydroxyurea quenches its catalytic radical, starving dividing cells of the nucleotides they need.
The enzyme that makes DNA building blocks from RNA building blocks. Gemcitabine's active form shuts it down and hydroxyurea quenches its catalytic radical, starving dividing cells of the nucleotides they need.
Large catalytic subunit of ribonucleotide reductase; target of gemcitabine diphosphate, with the small subunit RRM2 quenched by hydroxyurea.
No product in this corpus aims at Ribonucleotide reductase (RRM1) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Broadly expressed or essential: HPA lists RRM1 among essential proteins and finds the RNA at low tissue specificity; the 2 medicines aimed at it (Gemcitabine, Hydroxyurea (hydroxycarbamide)) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA RRM1: RNA low tissue specificity; high antibody staining in 7 normal tissues; highest cancer staining colorectal cancer (3 of 11 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Pancreatic ductal adenocarcinoma, Lung cancer (all types), Bladder & urothelial cancer); Open Targets associates it with 11 specific cancer types at or above 0.5 (non-small cell lung carcinoma, B-cell chronic lymphocytic leukemia, exocrine pancreatic carcinoma, ovarian carcinoma, melanoma, breast cancer and more). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas RRM1 tissue; Open Targets ENSG00000167325 associations
First described 1991. Earliest sequence paper UniProt cites for the protein: Parker N.J. et al, Nucleic Acids Res, 1991, "Human M1 subunit of ribonucleotide reductase: cDNA sequence and expression in stimulated lymphocytes". Source.
Large catalytic subunit of ribonucleotide reductase; target of gemcitabine diphosphate, with the small subunit RRM2 quenched by hydroxyurea.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Cerebral cortex, Colon, Epididymis, Esophagus, Gallbladder, Heart muscle.
Medium only: breast cancer, cervical cancer, endometrial cancer, head and neck cancer.
HPA RRM1 tissue · HPA RRM1 pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | Housekeeping enzyme present in every dividing cell (DNA building-block synthesis); not a selection marker, which is why these drugs are given by cancer type rather than by test. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"Ribonucleotide reductase" OR ABSTRACT:"Ribonucleotide reductase" OR TITLE:"RRM1" OR ABSTRACT:"RRM1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Ribonucleotide reductase (RRM1), not a curated reading list.