EHop-016

EHop-016 is a novel potent and selective inhibitor of Rac GTPase; inhibits Rac1 activity in MDA-MB-435 cells with an IC50 of 1.1 uM.IC50 value: 1.1 uM (MDA-MB-435 cell) [1]Target: Rac1 inhibitorin vitro: The IC(50) of 1.1 μM for Rac inhibition by EHop-016 is ～100-fold lower than for NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations of ≤5 μM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells that demonstrate high active levels of the Rac GEF Vav2, EHop-016 inhibits the association of Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac downstream effects of PAK1 (p21-activated kinase 1) activity and directed migration of metastatic cancer cells. Moreover, at effective concentrations (<5 μM), EHop-016 does not affect the viability of transformed mammary epithelial cells (MCF-10A) and reduces viability of MDA-MB-435 cells by only 20% [1]. At higher concentrations (10μM), EHop-016 inhibits the related Rho GTPase Cdc42, but not Rho, and also reduces cell viability. Moreover, EHop-016 inhibits the activation of the Rac downstream effector p21-activated kinase, extension of motile actin-based structures, and cell migration [2].in vivo: As quantified by UPLC MS/MS, EHop-016 was detectable in the plasma of nude mice at 17 to 23 ng/ml levels at 12 h following intraperitoneal (i.p.) administration of 10 to 25 mg/kg BW EHop-016. The EHop-016 mediated inhibition of angiogenesis In Vivo was confirmed by immunohistochemistry of excised tumors and by In Vitro tube formation assays of endothelial cells. Moreover, EHop-016 affected cell viability by down-regulating Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as increasing caspase 3/7 activities in metastatic cancer cells [3].

Signaling Pathways >> GPCR/G Protein >> Ras

Research Areas >> Cancer

[1]. Montalvo-Ortiz BL, et al. Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase. J Biol Chem. 2012 Apr 13;287(16):13228-38.

[2]. Dharmawardhane S, et al. Development of EHop-016: a small molecule inhibitor of Rac. Enzymes. 2013;33 Pt A:117-46.

[3]. Castillo-Pichardo L, et al. The Rac Inhibitor EHop-016 Inhibits Mammary Tumor Growth and Metastasis in a Nude Mouse Model. Transl Oncol. 2014 Oct 24;7(5):546-55.

ARS-853 | ARS-1620 | NSC 23766 | ML 141 | Salirasib | Pan-RAS-IN-1 | Rhosin hydrochloride | CASIN | EHT 1864 | 1A-116 | CCG 1423 | K-Ras(G12C) inhibitor 12 | ZCL 278 | Y16 | BQU57