2. Apoptosis
  3. IAP
  4. LCL161

LCL161 is a IAP inhibitor which inhibits XIAP in HEK293 cell and cIAP1 in MDA-MB-231 cell with IC50s of 35 and 0.4 nM, respectively.

For research use only. We do not sell to patients.

LCL161 Chemical Structure

LCL161 Chemical Structure

CAS No. : 1005342-46-0

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 132 In-stock
Solution
10 mM * 1 mL in DMSO USD 132 In-stock
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5 mg USD 120 In-stock
10 mg USD 156 In-stock
50 mg USD 360 In-stock
100 mg USD 576 In-stock
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Customer Review

Based on 30 publication(s) in Google Scholar

LCL161 Related Antibodies

Top Publications Citing Use of Products

29 Publications Citing Use of MCE LCL161

WB

    LCL161 purchased from MedChemExpress. Usage Cited in: J Med Chem. 2018 Jul 26;61(14):6350-6363.  [Abstract]

    IAP inhibitors induce degradation of IAP protein levels. MOLT4 cells are treated for 3 hr with 1 μM and propped for XIAP, cIAP1 or cIAP2. The β-actin blot is detected to ensure equal sample loading.

    View All IAP Isoform Specific Products:

    View All Isoforms
    cIAP cIAP-1 cIAP-2 XIAP

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    LCL161 is a IAP inhibitor which inhibits XIAP in HEK293 cell and cIAP1 in MDA-MB-231 cell with IC50s of 35 and 0.4 nM, respectively.

    IC50 & Target

    IC50: 35 nM (XIAP, in HEK293 cell), 0.40 nM (cIAP1, in MDA-MB-231)[1]
    In Vitro

    LCL161 shows anti-proliferative effects and reduces cell viability significantly in Hep3B (IC50=10.23 μM) and PLC5 (IC50=19.19 μM) cells in a dose-dependent manner. LCL161 induces apoptosis significantly in both the sensitive cell lines in a dose-dependent manner. LCL161 significantly down regulates the expression of cIAP1, starting at very low concentrations. LCL161 at low concentrations inhibits cIAP1 starting at the concentration of 0.5 nM[2]. LCL161 is a small molecule oral IAP antagonist in development for use in combination with cytotoxic agents. The effect of LCL161 on CYP3A4/5 (CYP3A) activity is investigated in vitro. Results in human liver microsomes indicated LCL161 inhibited CYP3A in a concentration- and time-dependent manner (KI of 0.797 μM and Kinact of 0.0803 min-1). LCL161 activates human PXR in a reporter gene assay and induced CYP3A4 mRNA up to ~5-fold in human hepatocytes[3].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    LCL161 Related Antibodies
    In Vivo

    Tumor-bearing mice are treated with vehicle or LCL161 p.o. at a dose of 50 mg/kg/day, or SC-2001 p.o. at a dose of 10 mg/kg/day, 5 days a week, or in combination for the duration of the study. Tumor growth is significantly inhibited by co-treatment with SC2001 and LCL161 and tumor size in the co-treatment group is only one third of that of the control group at the end of the study[2]. LCL161 is a first-in-class oral Smac mimetic shown to induce degradation of cIAP1 and cleavage of caspase 3 in mouse xenograft models[4].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Clinical Trial
    Molecular Weight

    500.63

    Formula

    C26H33FN4O3S
    CAS No.
    Appearance

    Solid

    Color

    White to yellow

    SMILES

    C[C@H](NC)C(N[C@@H](C1CCCCC1)C(N2[C@H](C3=NC(C(C4=CC=C(F)C=C4)=O)=CS3)CCC2)=O)=O
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (199.75 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.9975 mL 9.9874 mL 19.9748 mL
    5 mM 0.3995 mL 1.9975 mL 3.9950 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: 2.5 mg/mL (4.99 mM); Suspended solution; Need ultrasonic

      This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (4.99 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.91%

    COA (250 KB) LCMS (94 KB)

    Handling Instructions (2659 KB)
    References
    Cell Assay
    [3]

    Cells are plated (3×104 viable cells/well) in 96-well clear bottom white plates and the plates are incubated for ~24 hours at 37°C (5% CO2/95% air) in a humidified incubator. The cells (six replicate wells) are then treated with various concentrations (0.5, 1, 2.5, 5, 10, 25, or 50 µM) of LCL161, or vehicle control (0.1% DMSO, final concentration) for 24 hours in Puracyp dosing media. After the incubation period, the cells are washed with PBS, lysed and the luciferase substrate is added according to the vendor instructions. An aliquot of each well is transferred to the identical wells of black 96-well plates. The luminescence of each well is measured with a TopCount NXT Microplate Scintillation and Luminescence Counter. Cell viability is measured in separate plates treated identically to the PXR-reporter gene assay plates by measurement of ATP content of the cells using the CellTiter-Glo® Luminescent Cell Viability Assay kit. Cell viability is >80% for all treatments[3].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [2][4]

    Mice[2]
    Male NCr athymic nude mice (5-7 weeks of age) are used. Each mouse is inoculated s.c. in the dorsal flank with 1×106 Huh-7 cells suspended in 0.1 mL of serum-free medium containing 50% Matrigel. When tumors reach 200-300 mm3, mice receives LCL161 (50 mg/kg) or SC-2001 (10 mg/kg) p.o., or a combination of LCL161 and SC-2001, once daily. Controls receive vehicle. Tumors are measured weekly using calipers and their volumes calculated using the following standard formula: width2×length×0.52. LCL161 is a first-in-class oral Smac mimetic shown to induce degradation of cIAP1 and cleavage of caspase 3 in mouse xenograft models .
    Rats[4]
    LCL161 is administered orally, once weekly in 21-day cycles, at a starting dose of 10 mg (calculated by using one tenth of the dose that caused severe toxicity in 10% of rats and converted to a human-equivalent dose). In the MDA-MB-231 triple-negative breast cancer xenograft model, once-weekly and twice-daily LCL161 dosing are similarly efficacious. Once weekly is better tolerated, with reduced weight loss.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.9975 mL 9.9874 mL 19.9748 mL 49.9371 mL
    5 mM 0.3995 mL 1.9975 mL 3.9950 mL 9.9874 mL
    10 mM 0.1997 mL 0.9987 mL 1.9975 mL 4.9937 mL
    15 mM 0.1332 mL 0.6658 mL 1.3317 mL 3.3291 mL
    20 mM 0.0999 mL 0.4994 mL 0.9987 mL 2.4969 mL
    25 mM 0.0799 mL 0.3995 mL 0.7990 mL 1.9975 mL
    30 mM 0.0666 mL 0.3329 mL 0.6658 mL 1.6646 mL
    40 mM 0.0499 mL 0.2497 mL 0.4994 mL 1.2484 mL
    50 mM 0.0399 mL 0.1997 mL 0.3995 mL 0.9987 mL
    60 mM 0.0333 mL 0.1665 mL 0.3329 mL 0.8323 mL
    80 mM 0.0250 mL 0.1248 mL 0.2497 mL 0.6242 mL
    100 mM 0.0200 mL 0.0999 mL 0.1997 mL 0.4994 mL
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    LCL161 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    LCL1611005342-46-0LCL 161LCL-161IAPInhibitorinhibitorinhibit

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