ND1-YL2

Description: ND1-YL2 is a peptide-based PROTAC(R)Degrader of steroid receptor co-activator 1 (SRC-1, also known as nuclear receptor coactivator 1, NCOA1). ND1-YL2 is composed of a stapled peptide that binds SRC-1 (YL2) joined by a linker to a tetrapeptide that binds UBR box domains. Upon ternary complex formation, SRC-1 is polyubiquitinated and subsequently degraded via the N-degron pathway. This Degrader induces dose-dependent degradation of SRC-1 in the MDA-MB-231 triple negative breast cancer cell line (DC50 = 10 µM), and binds to the PAS-B domain of SRC-1 (Ki = 320 nM). ND1-YL2 inhibits MDA-MB-231 cell migrationin vitro, and suppresses metastasis of MDA-MB-231 cellsin vivo. References: Lee et al (2020) Targeted degradation of transcription co-activator SRC-1 through the N-degron pathway. Angew.Chem.Int.Ed. 59 17548