Evacetrapib

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Evacetrapib
Evacetrapib.svg
Identifiers
CAS number 1186486-62-3 YesY
ChemSpider 26286916 YesY
KEGG D10121 N
ChEMBL CHEMBL2017179 N
Jmol-3D images Image 1
Properties
Molecular formula C31H36F6N6O2
Molar mass 638.65 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Evacetrapib is a drug under development by Eli Lilly & Company (investigational name LY2484595) that 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.[1] The first CETP inhibitor, torcetrapib, was unsuccessful because it increased levels of the hormone aldosterone and increased blood pressure,[2] which led to excess cardiac events when it was studied.[2] Evacetrapib does not have the same effect.[1] When studied in a small clinical trial in people with elevated LDL and low HDL, significant improvements were noted in their lipid profile.[3]

Evacetrapib is one of two CETP inhibitors currently being evaluated (the other being anacetrapib).[1] Two other CETP inhibitors (torcetrapib and dalcetrapib) were discontinued during trials due to increased deaths and little identifiable cardiovascular benefit (despite substantial increases in HDL). Some hypothesize that CETP inhibitors may still be useful in the treatment of dyslipidemia, though significant caution is warranted.[2]

Trials[edit]

In a 2014 study in 165 Japanese patients Evacetrapib decreased CETP activity alone or in combination with atorvastatin.[4] Phase III trials are running with completion expected in 2016.[5] ACCELERATE is studying evacetrapib in participants with high-risk vascular disease. ACCENTUATE is studying patients with hyperlipidemia or diabetes.[6]

References[edit]

  1. ^ a b c Cao G, Beyer TP, Zhang Y, et al. (December 2011). "Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure". J. Lipid Res. 52 (12): 2169–76. doi:10.1194/jlr.M018069. PMC 3220285. PMID 21957197. 
  2. ^ a b c Joy T, Hegele RA (July 2009). "The end of the road for CETP inhibitors after torcetrapib?". Curr. Opin. Cardiol. 24 (4): 364–71. doi:10.1097/HCO.0b013e32832ac166. PMID 19522058. 
  3. ^ Nicholls SJ, Brewer HB, Kastelein JJ, Krueger KA, Wang MD, Shao M, Hu B, McErlean E, Nissen SE (2011). "Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol". JAMA 306 (19): 2099–109. doi:10.1001/jama.2011.1649. 
  4. ^ "Efficacy, safety, tolerability, and pharmacokinetic profile of evacetrapib administered as monotherapy or in combination with atorvastatin in Japanese patients with dyslipidemia.". Am J Cardiol. Jun 15, 2014. PMID 24786356. 
  5. ^ "A Study of Evacetrapib in High-Risk Vascular Disease (ACCELERATE)". 
  6. ^ "Study of Evacetrapib (LY2484595) in Participants With High Cholesterol (ACCENTUATE)".