p27 Y88 blocking peptide

p27 Y88 blocking peptide (also known as ALT or NP-ALT in its liposomal formulation) is a preclinical-stage peptide therapeutic developed by Concarlo Therapeutics. Derived from the SH3 domain of breast tumor kinase (Brk/PTK6), the peptide mimics Brk to bind to the cell cycle inhibitor protein p27Kip1 (CDKN1B). This binding blocks the Brk-mediated phosphorylation of p27 at tyrosine residue 88 (Y88), locking the p27-Cyclin D-CDK4 ternary complex in a closed, catalytically inactive conformation. Consequently, p27 is stabilized against ubiquitin-mediated degradation, allowing it to accumulate and simultaneously inhibit CDK4, CDK6, and CDK2. This coordinated inhibition of G1-phase cyclin-dependent kinases induces G1-phase cell cycle arrest and necroptosis. The compound is being investigated as a novel strategy to treat drug-resistant cancers, particularly hormone receptor-positive (HR+) and CDK4/6 inhibitor-resistant metastatic breast cancers.

Other names

Brk-SH3 peptideBrk-SH-3 peptideBrk-SH 3 peptidep27 tyrosine 88 blocking peptidep-27 tyrosine 88 blocking peptidep 27 tyrosine 88 blocking peptide