LXR623 - CAS 875787-07-8
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Not Intended for Therapeutic Use. For research use only.
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WAY-252623 (LXR-623) is a highly selective and orally bioavailable synthetic modulator of LXR, which can reduces total serum cholesterol and LDL cholesterol and inhibits lesion growth in models of atherosclerosis. IC50 values= 24 and 179 nM (for LXRβ and LXRα, respectively)
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≥ 98.0%
White solid powder
2-[(2-chloro-4-fluorophenyl)methyl]-3-(4-fluorophenyl)-7-(trifluoromethyl)indazole; 2-(2-chloro-4-fluorobenzyl)-3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazole; LXR 623; LXR-623; LXR623; WAY 252623; WAY-252623; WAY252623
Soluble to 100 mM in DMSO and to 100 mM in ethanol
A novel and potent LXR (liverX receptor) β-agonist used as a potential candidate for the treatment of atopic dermatitis IC50 values= 24 and 179 nM (for LXRβ and LXRα, respectively)
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In-house standard
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1.Biological Roles of Liver X Receptors in Immune Cells
Monica Pascual-Garcıa • Annabel F. Valledor. Arch. Immunol. Ther. Exp. (2012) 60:235–249
In addition to their role in sterol and glucose homeostasis, LXRs promote lipogenesis through the induction of sterol regulatory element-binding protein 1c (SREBP-1c) (Repa et al. 2000a) and carbohydrate response elementbinding protein (ChREBP) (Cha and Repa 2007). Both SREBP-1c and ChREBP are transcription factors that control the expression of molecules integral to fatty acid biosynthesis and esterification, and mice treated with panLXR agonists suffer a marked increase in plasma triglyceride levels (Schultz et al. 2000), which limit the potential therapeutic advantages of these agonists as anti-atherogenic or insulin-sensitizing drugs. Based on the fact that LXRa is more abundantly expressed than LXRb in the liver and accounts for most of the lipogenic effects of LXR agonists in this organ, alternative strategies try to identify compounds with higher selectivity for LXRb over LXRa to skip the hepatic lipogenic properties of general LXR agonists (Molteni et al. 2007; Ullrich et al. 2010). Also, two novel LXR agonists, WAY-252623 and N,N-dimethyl-3b-hydroxy-cholenamide, have been shown to reduce atherosclerotic lesion progression without inducing the expression of SREBP1c or activating hepatic lipogenesis, although the mechanisms involved in these selective actions have not been described (Kratzer et al. 2009; Quinet et al. 2009).
2.Liver X Receptors, Atherosclerosis and Inflammation
Daryn R. Michael & Tim G. Ashlin. Curr Atheroscler Rep (2012) 14:284–293
Currently, due to its progression towards phase I clinical trials, the most promising therapeutic target appears to be WAY-252623 (LXR-623), an indazole-based LXRβ modulator that has been shown to significantly reduce lesion progression in New Zealand white rabbits without affecting plasma cholesterol and triglyceride levels. Furthermore, WAY-252623 is also able to reduce plasma levels of total and LDL cholesterol and increase ABCA-1/G-1 expression in peripheral blood cells without having any marked effect on hepatic lipogenesis in cynomolgus monkeys. ABCA-1/G-1 expression levels have also been shown to be rapidly raised in the peripheral blood cells harvested from a representative human subject participating in an ongoing phase 1 SAD (Single Ascending Dose) clinical study of WAY-252623, suggesting that this agonist may be developed into a useful tool in the treatment of atherosclerosis.
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