Rational Design of Small Molecule Inhibitors Targeting the Ras GEF, SOS1
نویسندگان
چکیده
منابع مشابه
Rational design of small molecule inhibitors targeting RhoA subfamily Rho GTPases.
Rho GTPases have been implicated in diverse cellular functions and are potential therapeutic targets. By virtual screening, we have identified a Rho-specific inhibitor, Rhosin. Rhosin contains two aromatic rings tethered by a linker, and it binds to the surface area sandwiching Trp58 of RhoA with a submicromolar Kd and effectively inhibits GEF-catalyzed RhoA activation. In cells, Rhosin specifi...
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Rho GTPases have been implicated in diverse cellular functions and are potential therapeutic targets in inflammation, cancer, and neurologic diseases. Virtual screening of compounds that fit into surface grooves of RhoA known to be critical for guanine nucleotide exchange factor (GEF) interaction produced chemical candidates with minimized docking energy. Subsequent screening for inhibitory act...
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Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotide-exchange factor (GEF) that mediates intracellular signaling processes induced by receptor tyrosine kinases. In this study, we show that CIIA (also known as VPS28) physically associates with SOS1 and thereby inhibits the GEF activity of SOS1 on Ras, which prevents the epidermal growth factor (EGF)-induced activation of the Ras-Erk1/2...
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ژورنال
عنوان ژورنال: Chemistry & Biology
سال: 2014
ISSN: 1074-5521
DOI: 10.1016/j.chembiol.2014.09.018