product name Evacetrapib (LY2484595)
Description: Evacetrapib (also known as LY2484595) is a potent and selective inhibitor of CETP with IC50 of 5.5 nM, elevates HDL cholesterol without increases in aldosterone or blood pressure. Evacetrapib inhibits cholesterylester transfer protein, which transfers and thereby increases high-density lipoprotein and lowers low-density lipoprotein. It is thought that modifying lipoprotein levels modifies the risk of cardiovascular disease.
References: J Lipid Res. 2011 Dec;52(12):2169-76
638.65
Formula
C31H36F6N6O2
CAS No.
1186486-62-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 12.8 mg/mL (20.0 mM)
Water: <1 mg/mL
Ethanol: 12.8 mg/mL (20.0 mM)
Solubility (In vivo)
15% Captisol: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19406499
| In Vitro |
In vitro activity: Evacetrapib (LY2484595) inhibits human plasma CETP protein with IC50 of 26 nM. Evacetrapib (LY2484595) (< 10 μM) does not induce aldosterone or cortisol synthesis in H295R cells. Kinase Assay: Cell Assay: As a benzazepine-based inhibitor of CETP, evacetrapib is developed to increase HDL cholesterol for the treatment of coronary artery disease. Evacetrapib is efficacious both in vitro and in vivo. The IC50 values of evacetrapib against CETP are 5.5nM and 26nM, respectively in the buffer assay using human recombinant CETP and in the plasma assay using human plasma CETP. In the animal model of human CETP/ApoAI double transgenic mouse line, oral administration of evacetrapib at 30mg/kg significantly inhibits the CETP activity as well as increases the level of HDL. Besides that, the ED50 value of evacetrapib is less than 5mg/kg. Compared to the previous inhibitors of CETP, evacetrapib has less side effects. It is found no to increase blood pressure Zucker diabetic fatty rats and not to induce aldosterone or cortisol synthesis in H295R cells. |
|---|---|
| In Vivo | Evacetrapib (LY2484595) (30 mg/kg, orally) results in 98.4%, 98.6%, and 18.4% inhibition of CETP activity at 4 hours, 8 hours and 24 hours post dose respectively in human ApoAI and CETP double transgenic mice. Evacetrapib (LY2484595) (30 mg/kg) results in 129.7% increase in HDL-C 8 hours after oral administration. The ED50 values of CETP inhibitory activity 8 hours post oral dosing for Evacetrapib (LY2484595) in two dose-response studies are calculated to be 3.5 mg/kg and 4.1 mg/kg respectively. Evacetrapib (LY2484595) (< 200 mg/kg) does not increase blood pressure in Zucker diabetic fatty rats. |
| Animal model | Human ApoAI and CETP double transgenic mice |
| Formulation & Dosage | Dissolved in 10% acacia; 30 mg/kg; Oral gavage |
| References | J Lipid Res. 2011 Dec;52(12):2169-76 |
