ATSP-7041

**ATSP-7041** is a stapled α-helical peptide developed as a dual inhibitor of the E3 ubiquitin ligases **MDM2** and **MDMX (also known as MDM4)**. These proteins are primary negative regulators of the p53 tumor suppressor pathway, with overexpression in many human cancers leading to dysfunction of p53 and enabling unchecked cell growth. ATSP-7041 works by directly binding to and inhibiting both MDM2 and MDMX, thereby **reactivating wild-type p53 function** in tumors that retain a functional p53 gene but have inactivated it through overexpression of its inhibitors. The peptide demonstrates **potent, equipotent inhibition** of both targets, efficient cell membrane penetration, submicromolar cellular activity, and produces **prolonged activation of p53** signaling and robust tumor growth suppression in vivo. In addition to its main action, ATSP-7041 is a substrate and strong reversible inhibitor of **OATP1B1** and also inhibits **OATP1B3**, **P-glycoprotein (P-gp)**, and **breast cancer resistance protein (BCRP)**, raising the potential for clinically relevant drug-drug interactions via transporter inhibition. Its unique stapled peptide structure enables pharmacokinetic properties supportive of infrequent dosing regimens. Developed for both **solid and hematologic malignancies**, preclinical studies indicate effectiveness in models of breast and bone cancer. ATSP-7041 is a prototype molecule in ongoing efforts to bring stapled peptide drugs targeting intracellular protein-protein interactions to the clinic[1][3][6][7][8].