Ribonucleotide reductase large subunit (human) (RRM1)

Ribonucleotide reductase large subunit (RRM1) is the alpha/catalytic subunit of human ribonucleotide reductase, a critical enzyme essential for de novo synthesis of deoxyribonucleotides from ribonucleotides, which are required for DNA synthesis and repair. RRM1 forms an active heterodimer or higher-order oligomer with the small (RRM2 or RRM2B) subunit, and its proper activity governs the balance of DNA precursor pools, supporting cell division and genome integrity. As the large, catalytic subunit, RRM1 functions as the rate-limiting enzyme in de novo DNA precursor synthesis and exerts key regulatory control. Inhibitors of RRM1 (and the holoenzyme) are frontline cancer therapeutics, with several FDA-approved drugs acting via direct or indirect inhibition. Overexpression or dysregulation of RRM1 is associated with cancer, and its inhibition causes replication stress and cytotoxicity, making it a validated anticancer drug target. It is important to note that while the provided input referred to 'human ribonucleotide reductase R1 mRNA,' the canonical therapeutic target is the *protein* (enzyme), not its messenger RNA transcript, as direct mRNA targeting is not standard clinical practice for this target, but various protein inhibitors are approved or in development.

Other names

RRM1RR1Ribonucleoside-diphosphate reductase large subunitRibonucleotide reductase M1

Small molecules inhibit enzyme activity directly (blocking radical generation, binding the active site, or allosteric regulation) or disrupt subunit association.