Cyclin A RxL macrocyclic peptide inhibitor

Cyclin A RxL macrocyclic peptide inhibitors represent a novel class of cell-permeable, orally bioavailable peptidomimetics developed by Circle Pharma. These compounds are designed to target the Hydrophobic Patch (HP) on the surface of Cyclin A and Cyclin B, thereby blocking the RxL motif-mediated interactions between these cyclins and their substrates, such as E2F1. By disrupting the Cyclin A–E2F RxL interaction, these inhibitors hyperactivate E2F activity and selectively induce apoptosis in cancer cells with dysregulated RB1/pRB pathways. This therapeutic strategy is particularly relevant for small-cell lung cancer (SCLC), where RB1 and TP53 inactivation are common. Lead compounds like CIRc-004 have demonstrated significant in vivo tumor regression in preclinical models of SCLC, including chemotherapy-resistant variants.

Other names

Cyclin A/B RxL macrocyclic peptide inhibitor