GW3965 HCl
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MedKoo CAT#: 522685

CAS#: 405911-17-3 (HCl)

Description: GW-3965 is a liver X receptor agonist. GW3965 represses the production of pro-inflammatory cytokines by murine mast cells. GW3965 improves recovery from mild repetitive traumatic brain injury in mice partly through apolipoprotein E. GW3965 reduces tissue factor production and inflammatory responses in human islets in vitro. GW3965 dose-dependently regulates lps-mediated liver injury and modulates posttranscriptional TNF-alpha production and p38 mitogen-activated protein kinase activation in liver macrophages.


Chemical Structure

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GW3965 HCl
CAS# 405911-17-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 522685
Name: GW3965 HCl
CAS#: 405911-17-3 (HCl)
Chemical Formula: C33H32Cl2F3NO3
Exact Mass: 0.00
Molecular Weight: 618.520
Elemental Analysis: C, 64.08; H, 5.22; Cl, 11.46; F, 9.21; N, 2.26; O, 7.76

Price and Availability

Size Price Availability Quantity
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1650 Ready to ship
1g USD 2950 Ready to ship
2g USD 5250 Ready to ship
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Related CAS #: 405911-17-3 (HCl)   405911-09-3 (free)    

Synonym: GW-3965; GW3965; GW 3965; GW-3965 HCl; GW-3965 hydrochloride

IUPAC/Chemical Name: 2-(3-(3-((2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid hydrochloride

InChi Key: NMPUWJFHNOUNQU-UHFFFAOYSA-N

InChi Code: InChI=1S/C33H31ClF3NO3.ClH/c34-32-27(15-8-17-30(32)33(35,36)37)22-38(18-9-19-41-28-16-7-10-24(20-28)21-31(39)40)23-29(25-11-3-1-4-12-25)26-13-5-2-6-14-26;/h1-8,10-17,20,29H,9,18-19,21-23H2,(H,39,40);1H

SMILES Code: OC(CC1=CC(OCCCN(CC2=C(Cl)C(C(F)(F)F)=CC=C2)CC(C3=CC=CC=C3)C4=CC=CC=C4)=CC=C1)=O.Cl

Appearance: 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:

Biological target: GW3965 hydrochloride is a liver X receptor (LXR) agonist with EC50s of 190 nM and 30 nM for hLXRα and hLXRβ, respectively.
In vitro activity: NF-κB, a multi-subunit nuclear transcription factor, regulates the transcription of various cytokines and host immune responses. In quiescent cells, NF-κB is bound to its inhibitor IκB in the cytoplasm. Once stimulated, IκBα is phosphorylated and degraded. NF-κB is released and translocated into the nucleolus to regulate gene transcription. To explore the effect of GW3965 on the NF-κB signaling pathway in virus infection, the protein levels of IκBα, p65, phosphor-IκBα and phosphor-p65 were determined by Western blot. The results indicated that GW3965 suppressed the degradation of IκBα and the activation of NF-κB in a dose-dependent manner (Fig. 3). Reference: Arch Virol. 2016 Sep;161(9):2491-501. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087268/
In vivo activity: GW3965 treatment reduced systolic blood pressures in hypertensive rats. GW3965 treatment enhanced plasma nitrite levels in normotensive rats. KCl and phenylephrine (Phe)-induced vasocontractions were reduced in hypertensive groups and increased with GW3965 treatment. Expression of inositoltrisphosphate receptor1 (IP3R1) was increased by GW3965 in normotensive animals. The nuclear factor kappaB (NF-κB) and tumor necrosis factor alpha (TNF-α) expressions were increased in hypertensive rats and reduced by GW3965 treatment. These results indicate that the LXR agonist, GW3965, exhibited a beneficial effect on increased blood pressure and improved hypertension-induced impairment in contractile activity of vessel and inflammatory markers in vascular tissue. Reference: Life Sci. 2018 Nov 15;213:287-293. https://www.sciencedirect.com/science/article/abs/pii/S0024320518306672?via%3Dihub

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 32.34
DMSO 49.5 79.97
DMSO:PBS (pH 7.2) (1:4) 0.2 0.32
Ethanol 7.2 11.62

Preparing Stock Solutions

The following data is based on the product molecular weight 618.52 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.

Recalculate based on batch purity %
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. Han S, Bal NB, Sadi G, Usanmaz SE, Uludag MO, Demirel-Yilmaz E. The effects of LXR agonist GW3965 on vascular reactivity and inflammation in hypertensive rat aorta. Life Sci. 2018 Nov 15;213:287-293. doi: 10.1016/j.lfs.2018.10.042. Epub 2018 Oct 23. PMID: 30366037. 2. Cui X, Chopp M, Zacharek A, Cui Y, Roberts C, Chen J. The neurorestorative benefit of GW3965 treatment of stroke in mice. Stroke. 2013 Jan;44(1):153-61. doi: 10.1161/STROKEAHA.112.677682. Epub 2012 Nov 29. PMID: 23204055; PMCID: PMC3529962. 3. Sheng XX, Sun YJ, Zhan Y, Qu YR, Wang HX, Luo M, Liao Y, Qiu XS, Ding C, Fan HJ, Mao X. The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis. Arch Virol. 2016 Sep;161(9):2491-501. doi: 10.1007/s00705-016-2950-4. Epub 2016 Jun 29. PMID: 27357231; PMCID: PMC7087268.
In vitro protocol: 1. Sheng XX, Sun YJ, Zhan Y, Qu YR, Wang HX, Luo M, Liao Y, Qiu XS, Ding C, Fan HJ, Mao X. The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis. Arch Virol. 2016 Sep;161(9):2491-501. doi: 10.1007/s00705-016-2950-4. Epub 2016 Jun 29. PMID: 27357231; PMCID: PMC7087268.
In vivo protocol: 1. Han S, Bal NB, Sadi G, Usanmaz SE, Uludag MO, Demirel-Yilmaz E. The effects of LXR agonist GW3965 on vascular reactivity and inflammation in hypertensive rat aorta. Life Sci. 2018 Nov 15;213:287-293. doi: 10.1016/j.lfs.2018.10.042. Epub 2018 Oct 23. PMID: 30366037. 2. Cui X, Chopp M, Zacharek A, Cui Y, Roberts C, Chen J. The neurorestorative benefit of GW3965 treatment of stroke in mice. Stroke. 2013 Jan;44(1):153-61. doi: 10.1161/STROKEAHA.112.677682. Epub 2012 Nov 29. PMID: 23204055; PMCID: PMC3529962.

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1: Wang R, Li R, Wen Q, Peng K, Tan X, Chen Z. [Expression of LXR-β in human gastric cancer tissue and the effect of GW3965 on the proliferation of gastric cancer cell line SGC-7901]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016 Feb 28;41(2):127-33. doi: 10.11817/j.issn.1672-7347.2016.02.003. Chinese. PubMed PMID: 26932209.

2: Nunomura S, Okayama Y, Matsumoto K, Hashimoto N, Endo-Umeda K, Terui T, Makishima M, Ra C. Activation of LXRs using the synthetic agonist GW3965 represses the production of pro-inflammatory cytokines by murine mast cells. Allergol Int. 2015 Sep;64 Suppl:S11-7. doi: 10.1016/j.alit.2015.03.001. Epub 2015 Mar 31. PubMed PMID: 26344074.

3: Archer A, Stolarczyk E, Doria ML, Helguero L, Domingues R, Howard JK, Mode A, Korach-André M, Gustafsson JÅ. LXR activation by GW3965 alters fat tissue distribution and adipose tissue inflammation in ob/ob female mice. J Lipid Res. 2013 May;54(5):1300-11. doi: 10.1194/jlr.M033977. Epub 2013 Feb 27. PubMed PMID: 23446231; PubMed Central PMCID: PMC3622325.

4: Namjoshi DR, Martin G, Donkin J, Wilkinson A, Stukas S, Fan J, Carr M, Tabarestani S, Wuerth K, Hancock RE, Wellington CL. The liver X receptor agonist GW3965 improves recovery from mild repetitive traumatic brain injury in mice partly through apolipoprotein E. PLoS One. 2013;8(1):e53529. doi: 10.1371/journal.pone.0053529. Epub 2013 Jan 17. PubMed PMID: 23349715; PubMed Central PMCID: PMC3547922.

5: Cui X, Chopp M, Zacharek A, Cui Y, Roberts C, Chen J. The neurorestorative benefit of GW3965 treatment of stroke in mice. Stroke. 2013 Jan;44(1):153-61. doi: 10.1161/STROKEAHA.112.677682. Epub 2012 Nov 29. PubMed PMID: 23204055; PubMed Central PMCID: PMC3529962.

6: Stukas S, May S, Wilkinson A, Chan J, Donkin J, Wellington CL. The LXR agonist GW3965 increases apoA-I protein levels in the central nervous system independent of ABCA1. Biochim Biophys Acta. 2012 Mar;1821(3):536-46. doi: 10.1016/j.bbalip.2011.08.014. Epub 2011 Aug 26. PubMed PMID: 21889608.

7: Donkin JJ, Stukas S, Hirsch-Reinshagen V, Namjoshi D, Wilkinson A, May S, Chan J, Fan J, Collins J, Wellington CL. ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice. J Biol Chem. 2010 Oct 29;285(44):34144-54. doi: 10.1074/jbc.M110.108100. Epub 2010 Aug 25. PubMed PMID: 20739291; PubMed Central PMCID: PMC2962513.

8: Scholz H, Lund T, Dahle MK, Collins JL, Korsgren O, Wang JE, Foss A. The synthetic liver X receptor agonist GW3965 reduces tissue factor production and inflammatory responses in human islets in vitro. Diabetologia. 2009 Jul;52(7):1352-62. doi: 10.1007/s00125-009-1366-z. Epub 2009 May 5. PubMed PMID: 19415233.

9: Wang YY, Dahle MK, Steffensen KR, Reinholt FP, Collins JL, Thiemermann C, Aasen AO, Gustafsson JA, Wang JE. Liver X receptor agonist GW3965 dose-dependently regulates lps-mediated liver injury and modulates posttranscriptional TNF-alpha production and p38 mitogen-activated protein kinase activation in liver macrophages. Shock. 2009 Nov;32(5):548-53. doi: 10.1097/SHK.0b013e3181a47f85. PubMed PMID: 19295476.

10: Kotokorpi P, Ellis E, Parini P, Nilsson LM, Strom S, Steffensen KR, Gustafsson JA, Mode A. Physiological differences between human and rat primary hepatocytes in response to liver X receptor activation by 3-[3-[N-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)amino]propyloxy]phe nylacetic acid hydrochloride (GW3965). Mol Pharmacol. 2007 Oct;72(4):947-55. Epub 2007 Jul 12. PubMed PMID: 17628011.

11: Leik CE, Carson NL, Hennan JK, Basso MD, Liu QY, Crandall DL, Nambi P. GW3965, a synthetic liver X receptor (LXR) agonist, reduces angiotensin II-mediated pressor responses in Sprague-Dawley rats. Br J Pharmacol. 2007 Jun;151(4):450-6. Epub 2007 Apr 10. PubMed PMID: 17420776; PubMed Central PMCID: PMC2013964.