LXR-623

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种临床上可行的、高度脑渗透性的 LXRα-部分/LXRβ-完全激动剂，结合 Ki 为 33 nM/248 nM。

A clinically viable, highly brain-penetrant LXRα-partial/LXRβ-full agonist with binding Ki of 33 nM/248 nM; selectively kills GBM cells in an LXRβ- and cholesterol-dependent fashion, causing tumor regression and prolonged survival in mouse models. Atherosclerosis Phase 1 Discontinued(In Vitro):LXR-623 potently kills U87EGFRvIII and GBM39 cells in vitro while completely sparing NHAs. LXR-623 also increases ABCA1 protein and decreases LDLR protein levels in all three cell lines. LXR-623 suppresses LDLR expression, increases expression of the ABCA1 efflux transporter, and induces substantial cell death in all of the GBM samples tested. LXR-623 (5 μM) also induces GBM cell death through activation of LXRβ. LXR-623 treatment of human PBMC in vitro significantly increases transcription of ABCA1 and ABCG1.(In Vivo):LXR-623 (400 mg/kg, p.o.) crosses the blood-brain barrier, induces target gene expression, and achieves therapeutic levels in GBM cells in the brain with minimal activity in the periphery. LXR-623 inhibits tumor growth, promotes tumor cell death, and prolongs the survival of mice bearing intracranial patient-derived GBMs. LXR-623 (1.5, 5 mg/kg/day) significantly reduces progression of atherosclerosis in animals compared with the placebo group. WAY-252623 (15 and 50 mg/kg) results in a significant reduction of atherosclerosis in a dose-dependent manner. WAY-252623 (20, 60, and 120 mg/kg/day, p.o.) displays neutral lipid effects in this CETP-expressing Syrian hamster. Moreover, LXR-623 (50 mg/kg) induces gene expression in rodent peripheral blood cells in rat. LXR-623 (0, 15 and 50 mg/kg) dose-dependently upregulates transcription of ABCA1 and ABCG1 in monkey whole blood cells proportional to dose.

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WAY-252623 | LXR623 | LXR 623 | WAY252623 | WAY 252623

Nuclear Receptor/Transcription Factor

LXR

LXRα|LXRβ

Cardiovascular Disease

Atherosclerosis

875787-07-8

422.7784

C21H12ClF5N2

>98% (HPLC)

DMSO: ≥ 47 mg/mL

FC(C1=CC=CC2=C(C3=CC=C(F)C=C3)N(CC4=CC=C(F)C=C4Cl)N=C12)(F)F

2H-Indazole, 2-[(2-chloro-4-fluorophenyl)methyl]-3-(4-fluorophenyl)-7-(trifluoromethyl)-

(-20℃)

With Ice Pack

≥ 2 years