Discovery of selective LATS inhibitors scaffold hopping: enhancing drug-likeness and kinase selectivity for potential applications in regenerative medicine.

Due to its essential roles in cell proliferation and apoptosis, the precise regulation of the Hippo pathway through LATS presents a viable biological target for developing new drugs for cancer and regenerative diseases. However, currently available probes for selective and highly drug-like inhibition of LATS require further improvement in terms of both activity, selectivity and drug-like properties. Through scaffold hopping aided by docking studies and AI-assisted prediction of metabolic stabilities, we successfully identified an advanced LATS inhibitor demonstrating potent kinase activity, exceptional selectivity against other kinases, and superior oral pharmacokinetic profiles.

NUAK2 Inhibitors, KHKI-01128 and KHKI-01215, Exhibit Potent Anticancer Activity Against SW480 Colorectal Cancer Cells.

Background/aim: NUAK family kinase 2 (NUAK2) is a promising target for cancer therapeutics due to its reported role in protein phosphorylation, a critical process in cancer cell survival, proliferation, invasion, and senescence. This study aimed to identify novel inhibitors that disrupt NUAK2 activity. We have already identified two KRICT Hippo kinase inhibitor (KHKI) compounds, such as KHKI-01128 and KHKI-01215.

Synthesis and Properties of Pentafluorosulfanyl Group (SF)-Containing Meta-Diamide Insecticides.

Herein, we describe novel pentafluorosulfanyl (SF) group-containing meta-diamide insecticides. For the facile preparation of the SF-based compounds -, practical synthetic methods were applied. Among newly synthesized compounds, 3-benzamido--(2,6-dimethyl-4-(pentafluoro-λ-sulfanyl)phenyl)-2-fluorobenzamide showed (i) a high insecticidal activity, (ii) an excellent selectivity to insects, and (iii) good levels of water solubility and log P values.