product name EHT 1864
Description: EHT 1864 is a potent Rac family GTPase inhibitor with Kd of 40 nM, 50 nM, 60 nM and 250 nM for Rac1, Rac1b, Rac2 and Rac3, respectively. EHT 1864 attenuates glucose-stimulated insulin secretion in pancreatic β-cells. EHT 1864 specifically inhibits glucose-induced Rac1 activation and membrane association and associated downstream signaling events culminating in inhibition of GSIS.
References: J Biol Chem. 2007 Dec 7;282(49):35666-78; J Biol Chem. 2005 Nov 11;280(45):37516-25.
581.47
Formula
C25H29Cl2F3N2O4S
CAS No.
754240-09-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (172.0 mM)
Water: 100 mg/mL (172.0 mM)
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: EHT 1864 selectively inhibits Rac-induced lamellipodia formation, and specifically reverses cell transformation induced by constitutively activated mutants of Rac1 and Tiam1. EHT 1864 strongly impaires oncogenic Ras-induced cell proliferation in NIH 3T3 cells stably expressing H-Ras(61L) protein. EHT 1864 also reduces both extracellular and intracellular levels of Aβ peptides by inhibiting the γ-secretase-dependent cleavage of APP. In cultured hippocampal pyramidal neurons, EHT 1864, via inhibition of Rac1, rescues the phenotype induced by Rich2 knock-down. Kinase Assay: For inhibitor:GTPase binding analyses, aliquots of small GTPase solution (containing 1 μM inhibitor) are titrated into a solution of 1 μM inhibitor in the cuvette. Changes in fluorescence anisotropy are monitored at λex = 360 nm, λem = 440 nm, 30 s after each addition. All data analysis and curve fitting were performed using Microsoft Excel and QuantumSofts ProFit for Mac OS X. Cell Assay: NIH 3T3 cells stably expressing oncogenic Ras are plated in 96-well plates. The cells are cultured for up to 4 days in complete growth medium, either alone, or supplemented with 5 μM EHT 1864. Cell growth is then assessed using the conversion of MTT to a formazan product. Briefly, the MTT reagent (from a 5 mg/ml solution diluted in PBS) is added to the wells at a final concentration of 0.5 mg/ml, and the cells are further incubated for 4 h at 37°C. The medium is then removed, and the reaction is terminated by adding 100 μl/well Me2SO. The absorbance is read at 570 nm using a microplate reader. |
|---|---|
| In Vivo | EHT 1864 (40 mg/kg i.p.) significantly reduces Abeta 40 and Abeta 42 levels in guinea pig brains. |
| Animal model | Male Hartley albino guinea pigs |
| Formulation & Dosage | Dissolved in saline; 40 mg/kg daily; i.p. injection |
| References | J Biol Chem. 2007 Dec 7;282(49):35666-78; J Biol Chem. 2005 Nov 11;280(45):37516-25. |
