EHT 1864

EHT 1864 is a small molecule inhibitor of Rac1 signaling; modulate γ-Secretase-mediated APP processing.IC50 value:Target: Rac1 inhibitorin vitro: EHT 1864 blocks Aβ 40 and Aβ 42 production but does not impact sAPPα levels and does not inhibit γ-secretase. Rather, EHT 1864 modulates APP processing at the level of γ-secretase to prevent Aβ40 and Aβ42 generation. This effect does not result from a direct inhibition of the γ-secretase activity and is specific for APP cleavage, since EHT 1864 does not affect Notch cleavage [1]. EHT 1864 specifically inhibited Rac1-dependent platelet-derived growth factor-induced lamellipodia formation. Furthermore, our biochemical analyses with recombinant Rac proteins found that EHT 1864 possesses high affinity binding to Rac1, as well as the related Rac1b, Rac2, and Rac3 isoforms, and this association promoted the loss of bound nucleotide, inhibiting both guanine nucleotide association and Tiam1 Rac guanine nucleotide exchange factor-stimulated exchange factor activity in vitro [2].in vivo: EHT1864 significantly reduces Aβ 40 and Aβ 42 levels in guinea pig brains at a threshold that is compatible with delaying plaque accumulation and/or clearing the existing plaque in brain [1].

Signaling Pathways >> GPCR/G Protein >> Ras

Research Areas >> Neurological Disease

[1]. Desire L, et al. RAC1 inhibition targets amyloid precursor protein processing by gamma-secretase and decreases Abeta production in vitro and in vivo. J Biol Chem. 2005 Nov 11;280(45):37516-25.

[2]. Shutes A, et al. Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. J Biol Chem. 2007 Dec 7;282(49):35666-78.

[3]. Onesto C, et al. Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. Methods Enzymol. 2008;439:111-29.

ARS-853 | ARS-1620 | NSC 23766 | ML 141 | Salirasib | Pan-RAS-IN-1 | Rhosin hydrochloride | CASIN | EHop-016 | 1A-116 | CCG 1423 | K-Ras(G12C) inhibitor 12 | ZCL 278 | Y16 | BQU57