The PROTAC selectively degrading BCL-X inhibits the growth of tumors and significantly synergizes with Paclitaxel.

B-cell lymphoma extra large (BCL-X) is an important anti-apoptotic protein of BCL-2 family. It is frequently overexpressed in various hematologic and solid tumors, often positively correlated with chemotherapy resistance in tumors. However, the clinical development of the small molecule BCL-X inhibitor ABT-263 has been challenged on account of its on-target and dose-limiting toxicity.

Sorafenib and SIAIS361034, a novel PROTAC degrader of BCL-x, display synergistic antitumor effects on hepatocellular carcinoma with minimal hepatotoxicity.

The overexpression of BCL-x is closely associated with poor prognosis in hepatocellular carcinoma (HCC). While the strategy of combination of BCL-x and MCL-1 for treating solid tumors has been reported, it presents significant hepatotoxicity. SIAIS361034, a novel proteolysis targeting chimera (PROTAC) agent, selectively induces the ubiquitination and subsequent proteasomal degradation of BCL-x through the CRBN-E3 ubiquitin ligase.

Crosstalk among Reactive Oxygen Species, Autophagy and Metabolism in Myocardial Ischemia and Reperfusion Stages.

Myocardial ischemia is the most common cardiovascular disease. Reperfusion, an important myocardial ischemia tool, causes unexpected and irreversible damage to cardiomyocytes, resulting in myocardial ischemia/reperfusion (MI/R) injury. Upon stress, especially oxidative stress induced by reactive oxygen species (ROS), autophagy, which degrades the intracellular energy storage to produce metabolites that are recycled into metabolic pathways to buffer metabolic stress, is initiated during myocardial ischemia and MI/R injury.