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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
AZ-876 is a novel, potent high-affinity agonist of Liver X Receptor (LXR) with Ki values of 0.007 μM and 0.011 μM for human LXRα and LXRβ respectively. AZ876 protects against pathological cardiac hypertrophy and fibrosis without lipogenic side effects. LXR activation with AZ876 attenuated this increase, and significantly reduced TAC-induced increases in heart weight, myocardial fibrosis, and cardiac dysfunction without affecting blood pressure. Liver X receptors (LXRs) transcriptionally regulate inflammation, metabolism, and immunity.
| ln Vitro |
In isolated cardiac myocytes and fibroblasts, immunocytochemistry confirmed nuclear expression of LXRα in both these cell types. In cardiomyocytes, phenylephrine-stimulated cellular hypertrophy was significantly decreased in AZ876-treated cells. In cardiac fibroblasts, AZ876 prevented TGFβ- and angiotensin II-induced fibroblast collagen synthesis, and inhibited up-regulation of the myofibroblastic marker, α-smooth muscle actin. Plasma triglycerides and liver weight were unaltered following AZ876 treatment.[1]
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| ln Vivo |
Cardiac hypertrophy was induced in C57Bl6/J mice via transverse aortic constriction (TAC) for 6 weeks. During this period, mice received chow supplemented or not with AZ876 (20 µmol/kg/day). In murine hearts, LXRα protein expression was up-regulated ∼7-fold in response to TAC. LXR activation with AZ876 attenuated this increase, and significantly reduced TAC-induced increases in heart weight, myocardial fibrosis, and cardiac dysfunction without affecting blood pressure. At the molecular level, AZ876 suppressed up-regulation of hypertrophy- and fibrosis-related genes, and further inhibited prohypertrophic and profibrotic transforming growth factor β (TGFβ)-Smad2/3 signalling. [1]
APOE*3Leiden mice were fed an atherogenic diet alone or supplemented with either AZ876 (5 or 20µmol·kg(-1) ·day(-1) ) for 20 weeks. Total cholesterol and triglyceride levels were measured using commercial kits. Plasma cytokines were determined by using bead-based multiplex suspension array kits with the Luminex technology. Atherosclerosis was assessed histochemically and lesion composition was assessed by immunohistochemical methods. Low-dose AZ876 had no effect on plasma , whereas high-dose AZ876 increased plasma triglycerides (+110%) and reduced cholesterol (-16%) compared with controls. Low-dose AZ876 reduced lesion area (-47%); and high-dose AZ876 strongly decreased lesion area (-91%), lesion number (-59%) and severity. In either dose, AZ876 did not affect lesion composition. High-dose AZ876 , but not low-dose AZ876, reduced inflammation as reflected by lower cytokine levels and vessel wall activation.[2] |
| Animal Protocol |
AZ876 (20 µmol·kg−1·day−1,∼9·mg·kg−1·day−1)by oral gavage twice daily for 8 days[2]
After matching into four groups, based on age, plasma cholesterol and triglyceride levels, the mice received Western-type diet either alone (control group) or supplemented with AZ876 in a low dose (5 µmol·kg−1·day−1; ∼2 mg·kg−1·day−1) or high dose (20 µmol·kg−1·day−1; ∼9 mg·kg−1·day−1) or with GW3965 (17 µmol·kg−1·day−1; ∼10 mg·kd−1·day−1) (Joseph et al., 2002). Initially, the high dose of AZ876 was 10 µmol·kg−1·day−1; however, after 4 weeks of treatment, GW3965 induced hypertriglyceridaemia but AZ876 (10 µmol·kg−1·day−1) did not. Therefore, it was decided to increase the dose of AZ876 to 20 µmol·kg−1·day−1. After 20 weeks, mice were killed and the hearts, aortic root, livers and small intestine (duodenum) were isolated.[2] |
| References |
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| Molecular Formula |
C24H29N3O3S
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|---|---|
| Molecular Weight |
439.5704
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| Exact Mass |
439.192
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| CAS # |
898800-26-5
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| PubChem CID |
11655079
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| Appearance |
Yellow to orange solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
605.3±65.0 °C at 760 mmHg
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| Flash Point |
319.9±34.3 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.642
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| LogP |
3.27
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
789
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IVANYIPLGFVBGR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H29N3O3S/c1-24(2,3)27-23(28)21(22(31(27,29)30)18-10-6-4-7-11-18)25-19-12-14-20(15-13-19)26-16-8-5-9-17-26/h4,6-7,10-15,25H,5,8-9,16-17H2,1-3H3
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| Chemical Name |
2-(1,1-Dimethylethyl)-5-phenyl-4-[[4-(1-piperidinyl)phenyl]amino]-3(2H)-isothiazolone 1,1-dioxide
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| Synonyms |
AZ876; AZ 876; AZ-876, AZ12260493; AZ 12260493; AZ-12260493.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~227.50 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.69 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2750 mL | 11.3748 mL | 22.7495 mL | |
| 5 mM | 0.4550 mL | 2.2750 mL | 4.5499 mL | |
| 10 mM | 0.2275 mL | 1.1375 mL | 2.2750 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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