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    AT406 (SM-406, ARRY-334543)
    AT406 (SM-406, ARRY-334543)

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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 #: V0053
    CAS #: 1071992-99-8 (free base)Purity ≥98%

    Description: AT406 (also known as SM-406, ARRY-334543) is a novel, potent and orally bioavailable Smac/DIABLO mimetic and an antagonist of IAP (inhibitor of apoptosis protein via E3 ubiquitin ligase). It binds to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide. It has been shown to inhibit cancer cell growth in various human cancer cell lines and to induce apoptosis in xenograft tumors in mice

    References: Cancer Res. 2004 Oct 15;64(20):7183-90.

    Related CAS:1071992-57-8 (HCl salt)  

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    Molecular Weight (MW)561.71
    CAS No.1071992-99-8
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 100 mg/mL (178.0 mM) 
    Water: <1 mg/mL (slightly soluble or insoluble)
    Solubility (In vivo)30% Propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL
    Chemical Name/Synonym(5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxo-decahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide; AT-406; AT 406; AT406; SM-406, ARRY-334543; SM 406, ARRY 334543; SM406, ARRY334543; D 1143; Debio 1143; N65WC8PXDD; SM 406

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    In VitroAT-406 is a Smac mimetic and appears to mimic closely the AVPI peptide in both hydrogen bonding and hydrophobic interactions with XIAP, with additional hydrophobic contacts with W323 of XIAP. AT-406 is more sensitive to these IAPs than Smac AVPI peptide with 50-100 fold binding affinities. AT-406 (at 1 μM) completely restores the activity of caspase-9, which is suppressed by 500 nM XIAP BIR3 in a cell-free system.
    In VivoAT-406 has good pharmacokinetic (PK) properties and oral bioavailability in mice, rats, non-human primates, and dogs. In the MDA-MB-231 xenograft, AT-406 effectively induces cIAP1 degradation and processing of procaspase-8, cleavage of PARP in tumor tissues at 100 mg/kg with well toleration even at 200 mg/kg. AT-406 induces significant tumor growth inhibition with p of 0.0012 at 100 mg/kg.
    Animal modelMDA-MB-231 xenograft tumors in severe combined immune deficiency (SCID) mice
    Formulation & DosageHCl salt form of AT-406 in water; 10, 30, 100 mg/kg; Oral
    References[1] Cai Q, et al. J Med Chem, 2011, 54(8), 2714-2726.

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


    AT406 (SM-406, ARRY-334543)

    [1] Cai Q, et al. J Med Chem, 2011, 54(8), 2714-2726.

    AT406 (SM-406, ARRY-334543)

    [1] Cai Q, et al. J Med Chem, 2011, 54(8), 2714-2726.


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