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    LCL161
    LCL161

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0056
    CAS #: 1005342-46-0Purity ≥98%

    Description: LCL161 is a novel SMAC mimetic compound which potently binds to and inhibits multiple IAPs (i.e. XIAP, c-IAP), it inhibits XIAP in HEK293 cell and cIAP1 in MDA-MB-231 cell with IC50s of 35 and 0.4 nM, respectively. LCL161 showed significant inhibition of cell proliferation and viability in two human hepatocellular carcinoma (HCC) cells, Hep3B and PLC5. The IC50 values were 10 and 19 μM, respectively. However, LCL161 had no effect in the two other HCC cell lines, Sk-Hep1 (IC50 value of 224 μM) and Huh-7 (IC50 value of 228 μM). The difference of the effects is found to dependent on the expression of Bcl-2 in cells. For the ALL cells, LCL161 exerted growth inhibition with IC50 values of 9.3 and 0.25 μM, respectively. 

    References: Biochem Pharmacol. 2012 Aug 1;84(3):268-77; Pediatr Blood Cancer. 2012 Apr;58(4):636-9. 


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    Molecular Weight (MW)500.63
    FormulaC26H33FN4O3S
    CAS No.1005342-46-0
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: Soluble in DMSO > 10 mM
    Water: <1 mg/mL (slightly soluble or insoluble)
    Ethanol: 20 mg/mL warming (39.94 mM)
    Other info

    Synonym: LCL161; LCL 161; LCL-161

    Chemical Name: (S)-N-((S)-1-cyclohexyl-2-((S)-2-(4-(4-fluorobenzoyl)thiazol-2-yl)pyrrolidin-1-yl)-2-oxoethyl)-2-(methylamino)propanamide

    InChi Key: UFPFGVNKHCLJJO-SSKFGXFMSA-N

    InChi Code: InChI=1S/C26H33FN4O3S/c1-16(28-2)24(33)30-22(17-7-4-3-5-8-17)26(34)31-14-6-9-21(31)25-29-20(15-35-25)23(32)18-10-12-19(27)13-11-18/h10-13,15-17,21-22,28H,3-9,14H2,1-2H3,(H,30,33)/t16-,21-,22-/m0/s1

    SMILES Code: 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

    Chemical Name(2S)-N-[(1S)-1-cyclohexyl-2-[(2S)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide


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    In VitroLCL161 binds to inhibitors of apoptosis proteins (IAPs) with high affinity and initiates the destruction of cIAP1 and cIAP2, which further induces apoptosis via caspase activation. LCL161 modestly inhibits the growth of FLT3-ITD-expressing cells when administered alone, with an IC50 ranging from ~0.5 μM (Ba/F3-FLT3-ITD cells) to ~4 μM (MOLM13-luc+ cells).
    In VivoLCL161 significantly enhances the ability of PKC412 to inhibit the growth of Ba/F3-FLT3-ITD-luc+ cells in vivo. LCL161 is also shown to positively combine with the standard chemotherapeutic agents, Ara-c and doxorubicin, against FLT3-ITD-expressing cells and against D835Y-expressing cells. 
    Animal modelHuh-7 xeonograft nude mice
    Formulation & Dosage50 mg/kg; p.o.; q.d., for 20 days
    ReferencesBiochemical pharmacology, 2012, 84(3): 268-277.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    LCL161

    Weisberg E, et al. Leukemia, 2010, 24(12), 2100-2109.
     

    LCL161

    Effects of IAP inhibitor treatment and FLT3 inhibition, alone and combined, on the growth of mutant FLT3-expressing cells in vivo
     
    LCL161
    Effects of IAP inhibitor treatment and Abl inhibition, alone and combined, on the growth of BCR-ABL-expressing cells in vitro and in vivo


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