Baicalin Enhanced Oral Bioavailability of Sorafenib in Rats by Inducing Intestine Absorption.

Sorafenib (SOR) is an oral, potent, selective, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used as the first-line therapy for advanced hepatocellular carcinoma (HCC). Baicalin (BG) is used as adjuvant therapy for hepatitis, which accounts for the leading cause of the development of HCC, and is commonly coadministered with SOR in clinic. The purpose of the current study was to characterize the pharmacokinetic changes of SOR and the potential mechanism when SOR is administered concomitantly with BG in rats for single and multiple doses.

Development of hypoxia-activated PROTAC exerting a more potent effect in tumor hypoxia than in normoxia.

Hypoxia is a hallmark of many solid tumors, and it causes the overexpression of a variety of proteins including the epidermal growth factor receptor (EGFR). Many antitumor prodrugs have been designed to target hypoxia. Here we report the identification of a kind of hypoxia-activated proteolysis targeting chimera (ha-PROTAC) by introducing the hypoxia-activated leaving group (1-methyl-2-nitro-1-imidazol-5-yl)methyl or 4-nitrobenzyl into the structure of an EGFR-based PROTAC.

UPLC-MS/MS method for simultaneously determining nucleosides and methyl-nucleosides in liver mRNA of Epimedin C-induced liver injury mouse model.

Background: Epimedin C, one of the main active ingredients of Epimedium, has been reported to have potential hepatotoxicity. However, the mechanism of Epimedin C-induced liver injury has not been studied. mRNA methylation, mainly including N6-methyladenosine and N5-methylcytidine, is implicated in the regulation of many biological processes and diseases.