Discovery of Potent and Non-cytotoxic HDAC3-Selective Degraders Featuring a Propyl Hydrazide Zinc-Binding Group

Discovery of cyanocarbonimidodithioates as novel non-hydroxamate zinc-binding groups for selective HDAC8 inhibition: Design, synthesis, biological evaluation, anticancer activity, and in silico studies.

Design, synthesis, and screening of novel thienopyrimidine derivatives as PI3K/HDAC dual inhibitors against cervical cancer cells.

Although rapid systemic clearance currently limits its in vivo application, the potent cellular efficacy of B7 highlights its utility as a dual PI3K/HDAC lead compound, providing a distinct chemical scaffold for further structural optimization.

Development of a Potent and Isoform-Selective HDAC11 Inhibitor with Anti-Tumor Efficacy against Non-Small Cell Lung Cancer

Targeting histone deacetylase 11 (HDAC11) represents a promising therapeutic strategy, yet developing selective inhibitors for solid tumors remains a formidable challenge. Herein, we describe the rational lead optimization of a novel series of indole-based hydroxamic acids. Guided by our previous lead PB94, a systema...

Discovery of potent, selective, and orally bioavailable monocyclic pyridine-based PKMYT1 inhibitors that synergize with CHK1 inhibition in replication-stressed cancer cells.

PKMYT1 mediates the inhibitory phosphorylation of CDK1 and represents a promising synthetic lethal target in p53-deficient or CCNE1-amplified malignancies. A series of PKMYT1 inhibitors featuring a novel monocyclic pyridine core structure was discovered, exhibiting improved selectivity and enhanced drug-like properties...

Criteria-guided selection of alternative zinc-binding groups of HDAC3 inhibitors using in silico and in vitro approaches.

Histone deacetylases (HDACs) are epigenetic enzymes linked to several biological functions and diseases. Class I HDACs (HDAC1-3) share high protein sequence and active site similarity. Hydroxamate-based inhibitors, while highly potent, are non-selective with poor pharmacokinetic profile, prompting exploration of altern...

Design, synthesis, and biological evaluation of 2-aminopyrimidine-5-carboxamide derivatives as potent selective Wee1 inhibitors.

Wee1 is a serine/threonine kinase that plays an important role in regulating DNA damage response and cell cycle checkpoints. Inhibition of Wee1 could abrogate cell cycle arrest, exacerbate DNA damage, and induce mitotic catastrophe and apoptosis. Herein, a novel series of 2-aminopyrimidine-5-carboxamide derivatives wer...