Discovery of CLKs inhibitors for the treatment of non-small cell lung cancer.

Targeted inhibition of the Wnt pathway is a promising strategy for treating NSCLC. CDC2-like kinase 2 (CLK2), a dual-specificity kinase responsible for phosphorylating serine/arginine-rich (SR) proteins, can modulate Wnt signaling through the alternative splicing of Wnt target genes, making CLK2 an attractive therapeutic target for NSCLC. In this study, we report the synthesis, optimization, and evaluation of CLK2 inhibitors that effectively suppress the proliferation of NSCLC cells, with the identification of the lead compound LBM22.

Discovery of a photoactivatable dimerized STING agonist based on the benzo[]selenophene scaffold.

Stimulator of interferon genes (STING) agonism presents a powerful weapon for cancer immunotherapy. This study reports a novel dimerized STING agonist diBSP01, which exhibited promising STING binding and activation properties , based on the benzo[]selenophene scaffold. Meanwhile, shielding the pharmacophores of diBSP01 with photoremovable protecting groups (PPGs) resulted in the generation of the first photoactivatable STING agonist, caged-diBSP01, that exerted no biological potency in the absence of light stimulation while regaining its STING agonistic activity after 400 nm irradiation.

Preparing anti-SARS-CoV-2 agent EIDD-2801 by a practical and scalable approach, and quick evaluation machine learning.

EIDD-2801 is an orally bioavailable prodrug, which will be applied for emergency use authorization from the U.S. Food and Drug Administration for the treatment of COVID-19.