MDB5 is a Hedgehog pathway and Smoothened inhibitor that binds to the 7-TM domain of Smo . MDB5 reduces hepatic stellate cell activation, extracellular matrix-related gene expression, collagen deposition, hydroxyproline content and epithelial-mesenchymal transition, and prevents sinusoidal endothelial cell capillarization. MDB5 induces G1 and S phase cell cycle arrest, triggers apoptosis by upregulating Bax and downregulating Bcl-2 , and also decreases oxygen consumption rate, glucose uptake, transglutaminase activity and fibronectin matrix assembly. MDB5 reduces the levels of liver injury markers, hepatic triglyceride deposition and hepatic steatosis, restores the tissue structure of the kidney and spleen, and inhibits pancreatic tumor growth without causing body weight loss. MDB5 can be loaded into PEG-PCC-g-DC micelles, achieving high drug loading, sustained release, improved water solubility, enhanced cellular uptake and optimized hepatic distribution, with good tolerance in mice. MDB5 is applicable to research related to alcohol-associated liver disease, liver fibrosis and pancreatic cancer .
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