LOR-2501

LOR-2501 is a 20‑mer phosphorothioate antisense oligonucleotide designed to selectively downregulate expression of the R1 (RRM1) subunit of ribonucleotide reductase, a key enzyme required for de novo DNA synthesis and associated with tumor growth and chemoresistance.[1][2][4][7] By hybridizing to RRM1 mRNA, LOR-2501 promotes its degradation and reduces RRM1 protein levels, leading to impaired DNA synthesis and antitumor activity in a range of xenograft models including lung, liver, ovarian, brain, breast, and pancreatic cancers.[2][7] The drug was originally developed by Lorus Therapeutics (later Aptose Biosciences) and entered early‑phase clinical evaluation, including a phase 1 trial in patients with prostate cancer and other solid tumors, but its development has since been discontinued.[1][2][7][13]