Discovery and optimization of 4-(imidazo[1,2-a]pyrimidin-3-yl)thiazol-2-amine derivatives as novel phosphodiesterase 4 inhibitors.

Phosphodiesterases (PDEs) are important intracellular enzymes that hydrolyze the second messengers cAMP and/or cGMP. Now several studies have shown that PDE4 received particular attention due to which it represents the most prominent cAMP-metabolizing enzyme involved in many diseases. In this study, we performed prescreening of our internal compound library and discovered the compound (PTC-209) with moderate PDE4 inhibitory activity (IC of 4.

Synergistic Incorporation of Two ssDNA Activators Enhances the Trans-Cleavage of CRISPR/Cas12a.

CRISPR/Cas12a has been believed to be powerful in molecular detection and diagnostics due to its amplified trans-cleavage feature. However, the activating specificity and multiple activation mechanisms of the Cas12a system are yet to be elucidated fully. Herein, a "synergistic activator effect" is discovered, which supports an activation mechanism that a synergistic incorporation of two short ssDNA activators can promote the trans-cleavage of CRISPR/Cas12a, while either of them is too short to work independently.