Yazhou Wang, Chao Wang, Feng Ren, Alex Zhavoronkov, Xiao Ding
INTRODUCTION: PKMYT1, a member of the WEE family of kinases that regulates mitotic entry by phosphorylating CDK1 at Thr14, has recently gained prominence as a promising synthetic lethal target for oncology. Since the first-in-class PKMYT1 inhibitor entered clinical trials in 2021, the field has experienced explosive growth, marked by a surge in patents for both inhibitors and degraders and the advancement of five candidates into clinical development. AREAS COVERED: This review covers an update of clinical trial reports and patent literature on PKMYT1 inhibitors from 2021 to December 2025, drawing on patent retrieved from the World Intellectual Property Organization (WIPO), the European Patent Office, and the Cortellis Drug Discovery Intelligence database. EXPERT OPINION: The rapid advancement of PKMYT1 inhibitors and degraders underscores their potential as a synthetic‑lethal therapeutic strategy for cancers with CCNE1 amplification or FBXW7 alterations. Clinical proof‑of‑concept for this approach has been established by RP‑6306 trial outcomes, while insights from this comprehensive review are expected to inform strategies addressing the current limitations in this field.