Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Objective To investigate the effect of Qi-boosting & Yin-nourishing formula and purslane herb on expression of nitric oxide synthase (NOS) positive neuron in hippocampal CA1 area of diabetic rats. Methods The diabetic rat models were induced by intraperitoneal injection of streptozotocin. After prevented and treated with Qi-boosting & Yin-nourishing formula and purslane herb one month, the diabetic rats were killed, the expression of NOS was detected by NADPH-diaphorase histochemistry. Results The expression of NOS positive neuron in hippocampal CA1 area of diabetic rats which were prevented and treated with Qi-boosting & Yin-nourishing formula and purslane herb was increased (P