1. Metabolic Enzyme/Protease
  2. CETP

Evacetrapib (Synonyms: LY2484595)

Cat. No.: HY-13327
Handling Instructions

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

For research use only. We do not sell to patients.
Evacetrapib Chemical Structure

Evacetrapib Chemical Structure

CAS No. : 1186486-62-3

Size Price Stock Quantity
10 mM * 1 mL in DMSO $211 In-stock
5 mg $150 In-stock
10 mg $240 In-stock
50 mg $750 In-stock
100 mg $1250 In-stock
200 mg   Get quote  
500 mg   Get quote  

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    Evacetrapib purchased from MCE. Usage Cited in: Atherosclerosis. 2014 Aug;235(2):449-62.

    Downregulation of SREBP2-M by EVA and TOR reduced LDLR and PCSK9 expression. HepG2 cells are treated with EVA at indicated concentrations for 24 h. Total cell lysates (30 µg) are analyzed for the protein abundance of LDLR and β-actin. Nuclear and cytoplasmic extracts are isolated from each sample. Nuclear extracts of 30 µg protein per sample are used to detect SREBP2-M. The membrane is reprobed with anti-HDAC1. Cytoplasmic extracts of 30 µg protein per sample are used to detect SREBP2-P. The mem

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    • Biological Activity

    • Protocol

    • Technical Information

    • References

    Description

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

    IC50 & Target

    IC50: 5.5 nM (CETP)[1]

    In Vitro

    Evacetrapib is a novel benzazepine-based CETP inhibitor. In the buffer CETP assay, the absolute potency of the compound is 5.5 nM. In the human plasma CETP assay, the CETP concentration is about 2 μg/mL (25 nM) and the 36 nM IC50 value again indicates that Evacetrapib is a potent CETP inhibitor against either the recombinant protein or CETP from human plasma. Evacetrapib is apparently much more potent than Dalcetrapib[1].

    In Vivo

    In double transgenic mice expressing human CETP and apoAI, Evacetrapib exhibits an ex vivo CETP inhibition ED50 of less than 5 mg/kg at 8 h post oral dose and significantly elevated HDL cholesterol. Importantly, no blood pressure elevation is observed in rats dosed with Evacetrapib at high exposure multiples compared with the positive control, torcetrapib. Evacetrapib administered orally at 30 mg/kg results 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[1].

    Clinical Trial
    NCT Number Sponsor Condition Start Date Phase
    NCT02226653 Eli Lilly and Company Healthy Volunteers September 2014 Phase 1
    NCT01825889 Eli Lilly and Company Cardiovascular Disease April 2013 Phase 1
    NCT01903434 Eli Lilly and Company Healthy Volunteers July 2013 Phase 1
    NCT02497391 Eli Lilly and Company Healthy July 2015 Phase 1
    NCT02271425 Eli Lilly and Company Healthy Volunteers October 2014 Phase 1
    NCT01908582 Eli Lilly and Company Healthy Volunteers July 2013 Phase 1
    NCT02365558 Eli Lilly and Company Healthy January 2015 Phase 1
    NCT01736254 Eli Lilly and Company Healthy Volunteers December 2012 Phase 1
    NCT02168803 Eli Lilly and Company Dyslipidemia May 2014 Phase 1
    NCT01810432 Eli Lilly and Company Healthy Volunteers March 2013 Phase 1
    NCT02260635 Eli Lilly and Company Hypercholesterolemia November 2014 Phase 3
    NCT01836185 Eli Lilly and Company Hepatic Insufficiency April 2013 Phase 1
    NCT01687998 Eli Lilly and Company|The Cleveland Clinic Cardiovascular Diseases October 2012 Phase 3
    NCT02161731 Eli Lilly and Company Healthy Volunteers June 2014 Phase 1
    NCT01897493 Eli Lilly and Company Healthy Volunteers July 2013 Phase 1
    NCT01825876 Eli Lilly and Company Healthy Volunteers April 2013 Phase 1
    NCT01958489 Eli Lilly and Company Healthy Volunteers October 2013 Phase 1
    NCT01746732 Eli Lilly and Company Healthy Volunteers December 2012 Phase 1
    NCT02156492 Eli Lilly and Company Healthy Volunteers June 2014 Phase 1
    NCT02260648 Eli Lilly and Company Hypercholesterolemia January 2015 Phase 3
    NCT02227784 Eli Lilly and Company Hyperlipidemia October 2014 Phase 3
    NCT01450098 Eli Lilly and Company Healthy Volunteers October 2011 Phase 1
    NCT01537887 Eli Lilly and Company Healthy Volunteers February 2012 Phase 1
    NCT01448824 Eli Lilly and Company Healthy Subjects October 2011 Phase 1
    NCT01375075 Eli Lilly and Company Dyslipidemias June 2011 Phase 2
    NCT01105975 Eli Lilly and Company Dyslipidemia April 2010 Phase 2
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    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 1.5658 mL 7.8290 mL 15.6580 mL
    5 mM 0.3132 mL 1.5658 mL 3.1316 mL
    10 mM 0.1566 mL 0.7829 mL 1.5658 mL
    Kinase Assay
    [1]

    Human CETP cDNA is amplified from a human liver cDNA library and the sequence is confirmed to be identical to the published sequence. The cDNA is subcloned into a pcDNA3.1 vector, under the control of CMV promoter. A stable line is established in CV1 cells in which the above-mentioned construct is used to express the recombinant human CETP. The medium contained the secreted recombinant CETP protein and the amount (19 ng/μL) is quantified by an ELISA kit. The medium is then aliquoted in 0.2% BSA and stored at -80°C. The stock CETP protein is diluted 150-fold in CETP buffer (10 mM Tris, 150 mM NaCl, and 2 mM EDTA) before use. The assay is set up in a 96-well plate. Each well received 97.5 μL diluted CETP protein (final concentration 7 nM) and 2.5 μL of compound stock. After a 30 min incubation at 37°C, 5 μL of substrate stock (the same stock used in the human plasma CETP assay), 0.16 μL of VLDL stock (2.5 mg/mL, Intracel) and 145 μL of CETP buffer are added, and the incubation is continued for another 4 h. Signal is read for the human plasma CETP assay[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Evacetrapib is prepared in 10% acacia (Rat)[1].

    Rat[1]
    The blood pressure study is carried out using telemetered, male, obese Zucker Diabetic rats (ZDF fa/fa rats, 8 weeks of age on arrival; n=4). All rats underwent surgical implantation of a telemetry transmitter for continuous monitoring of hemodynamic parameters throughout the study. The rats are acclimated on Purina 5008 chow and house water ad libitum until 11 weeks of age. Mean daily blood pressure for the 24-h period immediately prior to administration of compound is taken as the baseline blood pressure. On the day of an experiment, a single 160 mg/kg dose (in 10% acacia) of Evacetrapib as the lysine salt is administered by oral gavage, and the drug effect is taken as the average daily mean arterial pressure (MAP) during the 24 h period following the dose. Data are expressed as the change in MAP from baseline. Following the last day of blood pressure monitoring, samples are collected from the orbital sinus at 1, 2, 4, 8, and 24 h post dose into tubes containing EDTA and processed into plasma. Plasma concentrations of Evacetrapib are measured using liquid chromatography tandem mass spectrometry. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    638.65

    Formula

    C₃₁H₃₆F₆N₆O₂

    CAS No.

    1186486-62-3

    Storage

    Please store the product under the recommended conditions in the Certificate of Analysis.

    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Inquiry Information

    Product Name:
    Evacetrapib
    Cat. No.:
    HY-13327
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