EHT 1864

Names

[ Name ]:
EHT 1864

[Synonym ]:
4H-Pyran-4-one, 2-(4-morpholinylmethyl)-5-[[5-[[7-(trifluoromethyl)-4-quinolinyl]thio]pentyl]oxy]-, hydrochloride (1:2)
2-(4-Morpholinylmethyl)-5-[(5-{[7-(trifluoromethyl)-4-quinolinyl]sulfanyl}pentyl)oxy]-4H-pyran-4-one dihydrochloride
2-(Morpholin-4-ylmethyl)-5-[(5-{[7-(trifluoromethyl)quinolin-4-yl]sulfanyl}pentyl)oxy]-4H-pyran-4-one dihydrochloride
eht 1864
EHT-1864

Biological Activity

[Description]:

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].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Ras

Research Areas >> Neurological Disease

[References]

[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.

[Related Small Molecules]

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

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₅H₂₉Cl₂F₃N₂O₄S

[ Molecular Weight ]:
581.475

[ Exact Mass ]:
580.117737

[ PSA ]:
90.10000

[ LogP ]:
6.92230

[ Appearance of Characters ]:
white to beige

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
H2O: soluble10mg/mL, clear

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Articles

Gq-mediated Akt translocation to the membrane: a novel PIP3-independent mechanism in platelets.

Blood 125(1) , 175-84, (2015)

Akt is an important signaling molecule regulating platelet aggregation. Akt is phosphorylated after translocation to the membrane through Gi signaling pathways by a phosphatidylinositol-3,4,5-trisphos...

Instructive roles for cytokine-receptor binding parameters in determining signaling and functional potency.

Sci. Signal. 8 , ra114, (2015)

Cytokines dimerize cell surface receptors to activate signaling and regulate many facets of the immune response. Many cytokines have pleiotropic effects, inducing a spectrum of redundant and distinct ...

An integrated imaging approach to the study of oxidative stress generation by mitochondrial dysfunction in living cells.

Environ. Health Perspect. 118 , 902-8, (2010)

The mechanisms of action of many environmental agents commonly involve oxidative stress resulting from mitochondrial dysfunction. Zinc is a common environmental metallic contaminant that has been impl...