910910-62-2Relevant articles and documents
Structural Basis for Binding and Selectivity of Antimalarial and Anticancer Ethylenediamine Inhibitors to Protein Farnesyltransferase
Hast, Michael A.,Fletcher, Steven,Cummings, Christopher G.,Pusateri, Erin E.,Blaskovich, Michelle A.,Rivas, Kasey,Gelb, Michael H.,Van Voorhis, Wesley C.,Sebti, Said M.,Hamilton, Andrew D.,Beese, Lorena S.
scheme or table, p. 181 - 192 (2010/08/19)
Protein farnesyltransferase (FTase) catalyzes an essential posttranslational lipid modification of more than 60 proteins involved in intracellular signal transduction networks. FTase inhibitors have emerged as a significant target for development of antic
Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites
Glenn, Matthew P.,Chang, Sung-Youn,Hornéy, Carrie,Rivas, Kasey,Yokoyama, Kohei,Pusateri, Erin E.,Fletcher, Steven,Cummings, Christopher G.,Buckner, Frederick S.,Pendyala, Prakash R.,Chakrabarti, Debopam,Sebti, Sa?d M.,Gelb, Michael,Van Voorhis, Wesley C.,Hamilton, Andrew D.
, p. 5710 - 5727 (2007/10/03)
Third world nations require immediate access to inexpensive therapeutics to counter the high mortality inflicted by malaria. Here, we report a new class of antimalarial protein farnesyltransferase (PFT) inhibitors, designed with specific emphasis on simple molecular architecture, to facilitate easy access to therapies based on this recently validated antimalarial target. This novel series of compounds represents the first Plasmodium falciparum selective PFT inhibitors reported (up to 145-fold selectivity), with lead inhibitors displaying excellent in vitro activity (IC50 50 100 nM). Initial studies of absorption, metabolism, and oral bioavailability are reported.
