LXR623 | CAS#875787-07-8 | liver X receptor-selective modulator

MedKoo Cat#: 510255 | Name: LXR623

Description:

WARNING: This product is for research use only, not for human or veterinary use.

LXR623, also known as WAY-252623, is a highly selective and orally bioavailable synthetic modulator of LXR, which demonstrated efficacy for reducing lesion progression in the murine LDLR(-/-) atherosclerosis model with no associated increase in hepatic lipogenesis either in this model or Syrian hamsters. In nonhuman primates with normal lipid levels, WAY-252623 significantly reduced total (50-55%) and LDL-cholesterol (LDLc) (70-77%) in a time- and dose-dependent manner as well as increased expression of the target genes ABCA1/G1 in peripheral blood cells.

Chemical Structure

LXR623

CAS#875787-07-8

Theoretical Analysis

MedKoo Cat#: 510255

Name: LXR623

CAS#: 875787-07-8

Chemical Formula: C21H12ClF5N2

Exact Mass: 422.0609

Molecular Weight: 422.78

Elemental Analysis: C, 59.66; H, 2.86; Cl, 8.39; F, 22.47; N, 6.63

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 400.00	Ready to ship
100mg	USD 700.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,550.00	Ready to ship
1g	USD 3,450.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

LXR623; LXR-623; LXR 623; WAY252623; WAY-252623; WAY 252623.

IUPAC/Chemical Name

2-(2-chloro-4-fluorobenzyl)-3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazole

InChi Key

KYWWJENKIMRJBI-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H12ClF5N2/c22-18-10-15(24)9-6-13(18)11-29-20(12-4-7-14(23)8-5-12)16-2-1-3-17(19(16)28-29)21(25,26)27/h1-10H,11H2

SMILES Code

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

Appearance

white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB61221

QC Data

View QC data: current batch, Lot#CRB61221

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

LXR-623 is a brain-penetrant partial LXRα and full LXRβ agonist, with IC50s of 24 nM and 179 nM, respectively.

In vitro activity:

It was hypothesized that the relatively low levels of endogenous LXR ligands in GBM cells would render them selectively sensitive to exogenous LXR ligands. The effect of exogenous administration of LXR ligands that are normally synthesized by cells in the presence of excess cholesterol was first tested. 24-OHC induced a dramatic dose-dependent increase in GBM cell death in vitro (Figure 1H, S1H). Importantly, NHAs, which synthesize 24-OHC (Figure 1G), were insensitive to exogenous 24-OHC administration (Figures 1H, S1H). Therefore, it was reasoned that synthetic LXR agonists might also kill GBM cells while sparing NHAs. The initial investigation was focused on LXR-623, a synthetic LXR agonist originally developed for cardiovascular indications and tested in patients (Hong and Tontonoz, 2014). Consistent with the proposed model, LXR-623 potently killed U87EGFRvIII and GBM39 cells in vitro while completely sparing NHAs (Figure 1I and S1I-L). LXR-623 also increased ABCA1 protein and decreased LDLR protein levels in all three cell lines (Figure 1J). These results prompted a deeper examination of LXR-623 as a potential therapy for GBM. Cancer Cell. 2016 Nov 14; 30(5): 683–693. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479636/

In vivo activity:

LXR-623 levels in the brains of nude mice treated daily by oral gavage were higher than plasma levels at two or eight hours after dosing (Figure 2A, S2B). Many of the undesirable hyperlipidemic effects of synthetic LXR agonists are mediated through LXRα in the liver and adipose tissue. The abilities of LXR-623 and GW3965 to induce target gene expression in the brain and peripheral tissues were compared. LXR-623 significantly induced the expression of LXR target genes Abcg1 and Idol in cerebral cortex tissue in a similar fashion to GW3965, and also induced Abca1. LXR-623 did not induce Srebp1c in cerebral cortex. LXR-623 also did not induce LXR target gene expression in the liver and epididymal white adipose tissue (eWAT) (Figure 2C-D). These data suggested that at least two special properties of LXR-623 – high CNS penetrance and reduced activity on LXRα – may provide a therapeutic window for treating GBM, and possibly other brain cancers.A pilot study of LXR-623 treatment in an in vivo intracranial GBM xenograft model was performed next. The potential relationship between intracranial GBM growth, as monitored by non-invasive fluorescence molecular tomography (FMT) imaging, and intratumoral LXR-623 levels were examined. As shown in Figure 2E, LXR-623 reached low-μM concentrations within intracranial GBMs, meeting or exceeding the concentrations required to kill GBM cells in culture (Figure 1I), and significantly reduced GBM tumor growth in vivo (Figure 2F). These data demonstrate favorable brain penetration and potent anti-GBM activity for LXR-623 in vivo. Cancer Cell. 2016 Nov 14; 30(5): 683–693. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479636/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	118.26
	Ethanol	52.0	123.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 422.78 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wan W, Hou Y, Wang K, Cheng Y, Pu X, Ye X. The LXR-623-induced long non-coding RNA LINC01125 suppresses the proliferation of breast cancer cells via PTEN/AKT/p53 signaling pathway. Cell Death Dis. 2019 Mar 13;10(3):248. doi: 10.1038/s41419-019-1440-5. PMID: 30867411; PMCID: PMC6416354. 2. Villa GR, Hulce JJ, Zanca C, Bi J, Ikegami S, Cahill GL, Gu Y, Lum KM, Masui K, Yang H, Rong X, Hong C, Turner KM, Liu F, Hon GC, Jenkins D, Martini M, Armando AM, Quehenberger O, Cloughesy TF, Furnari FB, Cavenee WK, Tontonoz P, Gahman TC, Shiau AK, Cravatt BF, Mischel PS. An LXR-Cholesterol Axis Creates a Metabolic Co-Dependency for Brain Cancers. Cancer Cell. 2016 Nov 14;30(5):683-693. doi: 10.1016/j.ccell.2016.09.008. Epub 2016 Oct 13. PMID: 27746144; PMCID: PMC5479636.

In vitro protocol:

In vivo protocol:

1: Giannarelli C, Cimmino G, Connolly TM, Ibanez B, Ruiz JM, Alique M, Zafar MU, Fuster V, Feuerstein G, Badimon JJ. Synergistic effect of liver X receptor activation and simvastatin on plaque regression and stabilization: an magnetic resonance imaging study in a model of advanced atherosclerosis. Eur Heart J. 2012 Jan;33(2):264-73. doi: 10.1093/eurheartj/ehr136. Epub 2011 May 23. PubMed PMID: 21606082. 2: Ratni H, Wright MB. Recent progress in liver X receptor-selective modulators. Curr Opin Drug Discov Devel. 2010 Jul;13(4):403-13. Review. PubMed PMID: 20597026. 3: Quinet EM, Basso MD, Halpern AR, Yates DW, Steffan RJ, Clerin V, Resmini C, Keith JC, Berrodin TJ, Feingold I, Zhong W, Hartman HB, Evans MJ, Gardell SJ, DiBlasio-Smith E, Mounts WM, LaVallie ER, Wrobel J, Nambi P, Vlasuk GP. LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse. J Lipid Res. 2009 Dec;50(12):2358-70. doi: 10.1194/jlr.M900037-JLR200. Epub 2009 Mar 24. PubMed PMID: 19318684; PubMed Central PMCID: PMC2781308.