Mouse Anti Human DMPK Hybridoma [NBOEN23 8F5H3]

Background: Salvia is the largest genus of family Lamiaceae and has nearly 1000 species. This genus produces several representative phytometabolites, e.g., diterpenoids and phenolic acids. The traditional uses in ethnomedicine and contemporary experimental studies have corroborated extensive therapeutic efficacy of Salvia plants. Drug metabolism and pharmacokinetic (DMPK) studies of Salvia natural products and their derivatives are indispensable in the optimization of lead compounds. New chemical entity with improved DMPK profiles is preferred. So far, there are few summaries concerning about the DMPK features of Salvia derived medicinal compounds. Tanshinones and Salvianolic acids raise concerns of herb-drug interaction. DMPK studies of various Salvia species, especially Salvia miltiorrhiza, are swiftly increasing. Objective: Here, the latest awareness, as well as the gaps of the DMPK issues in drug development and clinical usage of Salvia compounds, was highlighted. Conclusion: Herb-herb interactions of Salvia-containing traditional Chinese medicine (TCM) medicine pair/formula significantly impact the PK/pharmacodynamic performance of compounds thereof, which may inspire researchers to develop novel herbal formula. While the absorption, distribution, metabolism, elimination and toxicity (ADME/T) of some tanshinones and Salvianolic acids have been outlined, DMPK studies should be extended to more compounds, Salvia species, and Salvia-containing formulations. In the context of systems pharmacology, the DMPK knowledge base is expected to streamline the Salvia-based drug discovery and development.

Our research on hydantoin based TNF-alpha converting enzyme (TACE) inhibitors led to fused bi-heteroaryl hydantoin series that demonstrate sub-nanomolar potency (Ki) as well as excellent activity in human whole blood (hWBA). However, lead compound 2 posed some formulation challenges which prevented it for further development. A prodrug approach was investigated to address this issue. The pivalate pro drug 3 can be formulated as stable neutral form and demonstrated improved DMPK properties when compared with parent compound. (C) 2017 Elsevier Ltd. All rights reserved.