Design, Synthesis, and Computational Insights into PKMYT1 Inhibitors for the Treatment of Breast Cancer.

ABSTRACT: Background: Membrane-associated tyrosine-threonine protein kinase 1 (PKMYT1), which is identified as a synthetic lethal partner of CCNE1, emerged as a promising therapeutic target in oncology. Methods: A series of novel PKMYT1 inhibitors were designed by employing a pharmacophore fusion strategy. The underlying mechanisms were investigated by means of pharmacological experiments and molecular simulations. Results: Compound MY-14 demonstrated optimal kinase inhibition (IC₅₀ = 0.002 μM) and significant anti-proliferative efficacy against CCNE1-amplified cells (IC_50-HCC1569 = 1.06 μM and IC_50-OVCAR3 = 0.80 μM). Furthermore, MY-14 induced concentration-dependent apoptosis, inhibited colony formation, and effectively arrested c

SUBMITTER: Yu J 

PROVIDER: S-EPMC12467068 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature