1. Apoptosis
  2. IAP
  3. LCL161

LCL161 

Cat. No.: HY-15518 Purity: 99.17%
Handling Instructions

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

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 132 In-stock
Estimated Time of Arrival: December 31
5 mg USD 120 In-stock
Estimated Time of Arrival: December 31
10 mg USD 156 In-stock
Estimated Time of Arrival: December 31
50 mg USD 360 In-stock
Estimated Time of Arrival: December 31
100 mg USD 576 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 7 publication(s) in Google Scholar

Top Publications Citing Use of Products

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

    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.
    • 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].

    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].

    Clinical Trial
    Molecular Weight

    500.63

    Formula

    C₂₆H₃₃FN₄O₃S

    CAS No.

    1005342-46-0

    SMILES

    C[[email protected]](NC)C(N[[email protected]@H](C1CCCCC1)C(N2[[email protected]](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 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (199.75 mM; Need ultrasonic)

    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
    10 mM 0.1997 mL 0.9987 mL 1.9975 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

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

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

    *All of the co-solvents are provided by MCE.
    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

    Purity: 99.17%

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    Keywords:

    LCL161LCL 161LCL-161IAPInhibitorinhibitorinhibit

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