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A Next Generation PLD2 Inhibitor With Improved Physiochemical Properties and DMPK Profile for Translational in Vivo

Matthew C. O'Reilly, Sarah A. Scott, J. Scott Daniels, Ryan Morrison, Julie L. Engers, Thomas Oguin, Paul Thomas, H. Alex Brown, Craig W. Lindsley

PMID: 25834904

Abstract:

Further chemical optimization of our first generation phospholipase D2 (PLD2) probe (ML298) afforded ML395 (CID 73099363), a potent, >80-fold PLD2 selective allosteric inhibitor (cellular PLD1, IC50 >30,000 nM, cellular PLD2, IC50 = 360 nM). ML395 displays no inhibition of PLD1, displays exceptional solubility, stability and PK; therefore, ML395 is an improvement over our first generation PLD2 selective inhibitor, ML298. ML395 possesses favorable physiochemical and dystrophia myotonica-protein kinase (DMPK) properties, making it a useful tool to probe selective PLD2 function in vitro and in vivo. Data here shows therapeutic relevance in virology with no observed toxicity at very high doses.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1426916020 ML298 ML298 1426916-02-0 Price
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