Physicochemical Properties
| Molecular Formula | C20H19CL3N2O2S |
| Molecular Weight | 457.80 |
| Related CAS # | GSK2945;1438071-12-5 |
| Appearance | Light brown to brown solid powder |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | GSK2945 hydrochloride increases, in a dose-dependent manner (EC50 = 2.05 μM), the transcriptional activity of the Rev-erbα and Bmal1 (the target gene of REV-ERB) luciferase reporter genes. [1]. Cyp7a1/CYP7A1 levels in mouse and human primary hepatocytes are increased by treatment with GSK2945 hydrochloride (20 μM; 12 hours and 24 hours). Treatment with GSK2945 hydrochloride (20 μM) also raises the levels of Lrh-1/LRH-1 mRNA and protein, which is a recognized hepatic activator of Cyp7a1/CYP7A1 [1]. |
| ln Vivo | GSK2945 hydrochloride (0–10 mg/kg; intraperitoneal; twice daily for 7 days; male C57BL/6 mice) treatment lowered wild-type plasma cholesterol in rats and elevated mouse liver cholesterol 7α-hydroxylase (Cyp7a1) levels [1]. |
| Cell Assay |
RT-PCR[1] Cell Types: Mouse(male, CD1) and human(male, Caucasian) primary hepatocytes Tested Concentrations: 20 μM Incubation Duration: 12 hrs (hours) and 24 hrs (hours) Experimental Results: Led to significant increases in mRNA and protein(at 24- h) expression of Cyp7a1. mRNA and protein(at 24-h) levels of CYP7A1 were increased in human primary hepatocyte. Lrh-1/LRH-1 was upregulated. |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (8-10 weeks of age)[1] Doses: 0 mg/kg or 10 mg/kg Route of Administration: intraperitoneal (ip)injection; twice every day; for 7 days Experimental Results: Increased hepatic mouse cholesterol 7α- hydroxylase (Cyp7a1) level and lowered plasma cholesterol in wild-type mice. |
| References |
[1]. REV-ERBα Regulates CYP7A1 Through Repression of Liver Receptor Homolog-1. Drug Metab Dispos. 2018 Mar;46(3):248-258. |
Solubility Data
| Solubility (In Vitro) | DMSO :~20.83 mg/mL (~45.50 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.54 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1844 mL | 10.9218 mL | 21.8436 mL | |
| 5 mM | 0.4369 mL | 2.1844 mL | 4.3687 mL | |
| 10 mM | 0.2184 mL | 1.0922 mL | 2.1844 mL |