Small molecule inhibitors of dynamin I GTPase activity: development of dimeric tyrphostins

…, J Rusak, A Quan, R Abagyan, JL Scott…

Index: Hill, Timothy; Odell, Luke R.; Edwards, Jennifer K.; Graham, Mark E.; McGeachie, Andrew B.; Rusak, Jenny; Quan, Annie; Abagyan, Ruben; Scott, Janet L.; Robinson, Phillip J.; McCluskey, Adam Journal of Medicinal Chemistry, 2005 , vol. 48, # 24 p. 7781 - 7788

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Citation Number: 51

Abstract

Dynamin I is a GTPase enzyme required for endocytosis and is an excellent target for the design of potential endocytosis inhibitors. Screening of a library of tyrphostins, in our laboratory, against the GTPase activity of dynamin I gave rise to a μM potent lead, 2-cyano-3- (3, 4-dihydroxyphenyl) thioacrylamide (1, IC50 70 μM). Our initial investigations suggested that only the dimeric form of 1 displayed dynamin I GTPase inhibitory activity. Subsequent ...