Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases.

Abstract:

:There is now considerable experimental evidence that aberrant activation of Rho family small GTPases promotes uncontrolled proliferation, invasion, and metastatic properties of human cancer cells. Therefore, there is considerable interest in the development of small molecule inhibitors of Rho GTPase function. However, to date, most efforts have focused on inhibitors that block Rho GTPase function indirectly, either by targeting enzymes involved in post-translational processing or downstream protein kinase effectors. We have reported the identification and characterization of the EHT 1864 small molecule as an inhibitor of Rac family small GTPases, placing Rac1 in an inert and inactive state and then impairing Rac1-mediated functions in vivo. Our work suggests that EHT 1864 selectively inhibits Rac1 downstream signaling and cellular transformation by a novel mechanism involving guanine nucleotide displacement. This chapter provides the details for some of the biochemical and biological methods used to characterize the mode of action of EHT 1864 on Rac1 and its impact on Rac1-dependent cellular functions.

journal_name

Methods Enzymol

journal_title

Methods in enzymology

authors

Onesto C,Shutes A,Picard V,Schweighoffer F,Der CJ

doi

10.1016/S0076-6879(07)00409-0

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

111-29

eissn

0076-6879

issn

1557-7988

pii

S0076-6879(07)00409-0

journal_volume

439

pub_type

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