Evacetrapib | LY2484595 | CAS#1186486-62-3 | CETP inhibitor

MedKoo Cat#: 510227 | Name: Evacetrapib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Evacetrapib (LY2484595) is a novel benzazepine-based CETP inhibitor

Chemical Structure

Evacetrapib

CAS#1186486-62-3 (free base)

Theoretical Analysis

MedKoo Cat#: 510227

Name: Evacetrapib

CAS#: 1186486-62-3 (free base)

Chemical Formula: C31H36F6N6O2

Exact Mass: 638.2804

Molecular Weight: 638.65

Elemental Analysis: C, 58.30; H, 5.68; F, 17.85; N, 13.16; O, 5.01

Price and Availability

Size	Price	Availability
100mg	USD 1,450.00	2 Weeks
200mg	USD 2,450.00	2 Weeks
500mg	USD 3,950.00	2 Weeks
1g	USD 4,950.00	2 Weeks
2g	USD 7,950.00	2 Weeks

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Related CAS #

1186486-62-3 (free base) 1259393-05-9 (monohydrate)

Synonym

LY2484595; LY 2484595; LY-2484595; Evacetrapib.

IUPAC/Chemical Name

(1S,4r)-4-(((S)-5-((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)methyl)cyclohexanecarboxylic acid

InChi Key

IHIUGIVXARLYHP-YBXDKENTSA-N

InChi Code

InChI=1S/C31H36F6N6O2/c1-18-11-19(2)27-25(12-18)26(5-4-10-42(27)16-20-6-8-22(9-7-20)28(44)45)43(29-38-40-41(3)39-29)17-21-13-23(30(32,33)34)15-24(14-21)31(35,36)37/h11-15,20,22,26H,4-10,16-17H2,1-3H3,(H,44,45)/t20-,22-,26-/m0/s1

SMILES Code

O=C([C@H]1CC[C@H](CN2C3=C(C)C=C(C)C=C3[C@@H](N(CC4=CC(C(F)(F)F)=CC(C(F)(F)F)=C4)C5=NN(C)N=N5)CCC2)CC1)O

Appearance

white 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

Evacetrapib is one of two CETP inhibitors currently being evaluated (the other being anacetrapib). 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. (source: http://en.wikipedia.org/wiki/Evacetrapib).

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Evacetrapib is a CETP inhibitor, which inhibits human recombinant CETP protein (IC50 5.5 nM) and CETP activity in human plasma (IC50 36 nM) in vitro.

In vitro activity:

The in vitro activity of evacetrapib against CETP was first tested in the buffer CETP assay, in which human recombinant CETP protein was used as the source for the protein activity. The concentration of the compound causing half-maximum inhibition of CETP activity in this assay was 5.5 nM. This compares to 25.2 nM for torcetrapib and 21.5 nM for anacetrapib in the same assay. Reference: J Lipid Res. 2011 Dec;52(12):2169-2176. https://pubmed.ncbi.nlm.nih.gov/21957197/

In vivo activity:

Evacetrapib administered orally at 30 mg/kg resulted in 98.4%, 98.6%, and 18.4% inhibition of CETP activity at 4, 8 and 24 h post dose respectively. Evacetrapib dosed orally at 30 mg/kg resulted in 129.7% increase in HDL-C 8 h after oral administration (Fig. 2A, B). The efficacy of evacetrapib was comparable to that of torcetrapib. Reference: J Lipid Res. 2011 Dec;52(12):2169-2176. https://pubmed.ncbi.nlm.nih.gov/21957197/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.6	74.53
	DMF	30.0	46.97
	Ethanol	21.4	33.51

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 638.65 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.

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. Cao G, Beyer TP, Zhang Y, Schmidt RJ, Chen YQ, Cockerham SL, Zimmerman KM, Karathanasis SK, Cannady EA, Fields T, Mantlo NB. 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. 2011 Dec;52(12):2169-2176. doi: 10.1194/jlr.M018069. Epub 2011 Sep 25. PMID: 21957197; PMCID: PMC3220285.

In vitro protocol:

In vivo protocol:

1: Nicholls SJ. Evacetrapib. Curr Cardiol Rep. 2012 Jun;14(3):245-50. doi: 10.1007/s11886-012-0252-3. PMID: 22362199. 2: Eyvazian VA, Frishman WH. Evacetrapib: Another CETP Inhibitor for Dyslipidemia With No Clinical Benefit. Cardiol Rev. 2017 Mar/Apr;25(2):43-52. doi: 10.1097/CRD.0000000000000137. PMID: 28099220. 3: Phénix J, Côté J, Dieme D, Recinto SJ, Oestereich F, Efrem S, Haddad S, Bouchard M, Munter LM. CETP inhibitor evacetrapib enters mouse brain tissue. Front Pharmacol. 2023 Jul 18;14:1171937. doi: 10.3389/fphar.2023.1171937. PMID: 37533630; PMCID: PMC10390775. 4: Sahebkar A, Simental-Mendía LE, Guerrero-Romero F, Golledge J, Watts GF. Efficacy and Safety of Evacetrapib for Modifying Plasma Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr Pharm Des. 2016;22(5):595-608. doi: 10.2174/1381612822666151125000035. PMID: 26601964. 5: Lincoff AM, Nicholls SJ, Riesmeyer JS, Barter PJ, Brewer HB, Fox KAA, Gibson CM, Granger C, Menon V, Montalescot G, Rader D, Tall AR, McErlean E, Wolski K, Ruotolo G, Vangerow B, Weerakkody G, Goodman SG, Conde D, McGuire DK, Nicolau JC, Leiva-Pons JL, Pesant Y, Li W, Kandath D, Kouz S, Tahirkheli N, Mason D, Nissen SE; ACCELERATE Investigators. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease. N Engl J Med. 2017 May 18;376(20):1933-1942. doi: 10.1056/NEJMoa1609581. PMID: 28514624. 6: Filippatos TD, Elisaf MS. Evacetrapib and cardiovascular outcomes: reasons for lack of efficacy. J Thorac Dis. 2017 Aug;9(8):2308-2310. doi: 10.21037/jtd.2017.07.75. PMID: 28932532; PMCID: PMC5594181. 7: Nicholls SJ, Bubb K. The mystery of evacetrapib - why are CETP inhibitors failing? Expert Rev Cardiovasc Ther. 2020 Mar;18(3):127-130. doi: 10.1080/14779072.2020.1745633. Epub 2020 Mar 21. PMID: 32200670. 8: Chen Y, Dong J, Zhang X, Chen X, Wang L, Chen H, Ge J, Jiang XC. Evacetrapib reduces preβ-1 HDL in patients with atherosclerotic cardiovascular disease or diabetes. Atherosclerosis. 2019 Jun;285:147-152. doi: 10.1016/j.atherosclerosis.2019.04.211. Epub 2019 Apr 14. PMID: 31054484; PMCID: PMC6548311. 9: Doggrell SA. No cardiovascular benefit with evacetrapib - is this the end of the road for the 'cetrapibs'? Expert Opin Pharmacother. 2017 Oct;18(14):1439-1442. doi: 10.1080/14656566.2017.1365838. Epub 2017 Aug 14. PMID: 28799819. 10: Hu L, Dong H, He L, Shi M, Xiang N, Su Y, Wang C, Tian Y, Hu Y, Wang H, Liu H, Wen C, Yang X. Evacetrapib Elicits Antitumor Effects on Colorectal Cancer by Inhibiting the Wnt/β-Catenin Signaling Pathway and Activating the JNK Signaling Pathway. Biol Pharm Bull. 2022;45(9):1238-1245. doi: 10.1248/bpb.b22-00053. PMID: 36047191. 11: Cannady EA, Wang MD, Friedrich S, Rehmel JL, Yi P, Small DS, Zhang W, Suico JG. Evacetrapib: in vitro and clinical disposition, metabolism, excretion, and assessment of drug interaction potential with strong CYP3A and CYP2C8 inhibitors. Pharmacol Res Perspect. 2015 Oct;3(5):e00179. doi: 10.1002/prp2.179. Epub 2015 Oct 12. PMID: 26516590; PMCID: PMC4618649. 12: Schmidt AF, Hunt NB, Gordillo-Marañón M, Charoen P, Drenos F, Kivimaki M, Lawlor DA, Giambartolomei C, Papacosta O, Chaturvedi N, Bis JC, O'Donnell CJ, Wannamethee G, Wong A, Price JF, Hughes AD, Gaunt TR, Franceschini N, Mook- Kanamori DO, Zwierzyna M, Sofat R, Hingorani AD, Finan C. Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease. Nat Commun. 2021 Sep 24;12(1):5640. doi: 10.1038/s41467-021-25703-3. PMID: 34561430; PMCID: PMC8463530. 13: Bahbah EI, Shehata MSA, Alnahrawi SI, Sayed A, Menshawey A, Fisal A, Morsi M, Gabr ME, Elbasit MSA. Safety and Efficacy of Evacetrapib in Patients with Inadequately-controlled Hypercholesterolemia and High Cardiovascular Risk; A meta-analysis of Randomized Placebo-controlled Trials. Prostaglandins Leukot Essent Fatty Acids. 2021 May;168:102282. doi: 10.1016/j.plefa.2021.102282. Epub 2021 Apr 12. PMID: 33882411. 14: Nicholls SJ, Ruotolo G, Brewer HB, Wang MD, Liu L, Willey MB, Deeg MA, Krueger KA, Nissen SE. Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients. J Clin Lipidol. 2016 May-Jun;10(3):519-527.e4. doi: 10.1016/j.jacl.2015.11.014. Epub 2015 Dec 18. PMID: 27206939. 15: Suico JG, Friedrich S, Krueger KA, Zhang W. Evacetrapib at a supratherapeutic steady state concentration does not prolong QT in a thorough QT/QTc study in healthy participants. J Cardiovasc Pharmacol Ther. 2014 May;19(3):283-9. doi: 10.1177/1074248413510784. Epub 2013 Nov 22. PMID: 24271137. 16: Aronow WS. Effect of evacetrapib on cardiovascular outcomes in patients with high-risk cardiovascular disease. J Thorac Dis. 2017 Jul;9(7):1822-1825. doi: 10.21037/jtd.2017.06.106. PMID: 28839974; PMCID: PMC5542999. 17: Menon V, Kumar A, Patel DR, St John J, Riesmeyer J, Weerakkody G, Ruotolo G, Wolski KE, McErlean E, Cremer PC, Nicholls SJ, Lincoff AM, Nissen SE. Effect of CETP inhibition with evacetrapib in patients with diabetes mellitus enrolled in the ACCELERATE trial. BMJ Open Diabetes Res Care. 2020 Mar;8(1):e000943. doi: 10.1136/bmjdrc-2019-000943. PMID: 32179516; PMCID: PMC7073792. 18: Cao G, Beyer TP, Zhang Y, Schmidt RJ, Chen YQ, Cockerham SL, Zimmerman KM, Karathanasis SK, Cannady EA, Fields T, Mantlo NB. 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. 2011 Dec;52(12):2169-2176. doi: 10.1194/jlr.M018069. Epub 2011 Sep 25. PMID: 21957197; PMCID: PMC3220285. 19: Simic B, Mocharla P, Crucet M, Osto E, Kratzer A, Stivala S, Kühnast S, Speer T, Doycheva P, Princen HM, van der Hoorn JW, Jukema JW, Giral H, Tailleux A, Landmesser U, Staels B, Lüscher TF. Anacetrapib, but not evacetrapib, impairs endothelial function in CETP-transgenic mice in spite of marked HDL-C increase. Atherosclerosis. 2017 Feb;257:186-194. doi: 10.1016/j.atherosclerosis.2017.01.011. Epub 2017 Jan 16. PMID: 28152406. 20: Friedrich S, Kastelein JJ, James D, Waterhouse T, Nissen SE, Nicholls SJ, Krueger KA. The pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of evacetrapib administered as monotherapy or in combination with statins. CPT Pharmacometrics Syst Pharmacol. 2014 Jan 22;3(1):e94. doi: 10.1038/psp.2013.70. PMID: 24452615; PMCID: PMC3910017. 6: Cao G, Beyer TP, Zhang Y, Schmidt RJ, Chen YQ, Cockerham SL, Zimmerman KM, Karathanasis SK, Cannady EA, Fields T, Mantlo NB. 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. 2011 Dec;52(12):2169-76. doi: 10.1194/jlr.M018069. Epub 2011 Sep 25. PubMed PMID: 21957197; PubMed Central PMCID: PMC3220285.