CID-078

CID-078 is an orally bioavailable macrocycle and a first-in-class dual cyclin A and B RxL inhibitor developed by Circle Pharma. It selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation, particularly those with high E2F activity. The drug works by potently and selectively disrupting the protein-to-protein interactions between cyclins A and B and their key substrates (including E2F for cyclin A, Myt1 for cyclin B), leading to cell cycle arrest at the G2/M phase, DNA damage, mitotic arrest, and apoptotic tumor cell death. Preclinical studies have shown single-agent tumor regressions in models of small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), triple negative breast cancer (TNBC), neuroendocrine carcinoma, neuroendocrine tumors, as well as ER+/HER2– breast cancers that progress on CDK4/6 inhibitors. The mechanism exploits synthetic lethality in cancers with dysregulated cell cycle control. As of 2024, CID-078 is being evaluated in a Phase 1 clinical trial for advanced solid tumors[1][2][5][8].

Other names

cyclin A/B RxL inhibitor CID-078