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Scaffold Hopping Affords a Highly Selective

Xinmin Xie, John T. Brogan, Michael L. Schulte, Debbie Mi, Haibo Yu, Eric S. Dawson, Min Li, Owen McManus, Julie Engers, L. Michelle Lewis, Analisa Thompson, Carrie K. Jones, C. David Weaver, Craig W. Lindsley

PMID: 23762962

Abstract:

A scaffold hopping approach afforded ML218 (CID 45115620) a selective T-Type Ca2+ (Cav3.1, Cav3.2, Cav3.3) inhibitor (Cav3.2, IC50 = 150 nM in Ca2+ flux; Cav3.2 IC50 = 310 nM and Cav3.3 IC50 = 270 nM in patch clamp electrophysiology) suitable for in vitro and in vivo studies. ML218 possess excellent dystrophia myotonica protein kinase (DMPK) properties, acceptable in vivo rat PK, excellent brain levels and was efficacious upon oral dosing in a preclinical Parkinsonian model. Thus, ML218 is a powerful new probe to study T-Type Ca2+ function in vitro and in vivo.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1346233688 ML218 ML218 1346233-68-8 Price
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