SM-164

- Overview
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    Background
    
    SM-164 is a bivalent mimetic of Smac with Ki values of 0.31 nM, 1.1 nM and 0.56 nM for cIAP-1, cIAP-2 and XIAP, respectively 1.
    SM-164 is developed as an anticancer agent. It plays its antitumor roles through inducing degradation of cellular inhibitor of apoptosis protein (cIAP)-1/2, antagonizing X-linked inhibitor of apoptosis protein (XIAP) and inducing TNFα-dependent apoptosis in tumor cells. SM-164 is a bivalent mimetic containing two SM-122 analogues. It binds to cIAP-1 protein containing bothBIR2 and BIR3 domains, cIAP-2 BIR3 protein and XIAP protein containing both BIR2 and BIR3 domains with Ki values of 0.31 nM, 1.1 nM and 0.56 nM, respectively. In tumor cells, treatment of SM-164 significantly reduced cIAP-1 level to undetectable levels (1 nM, 60 min), effectively antagonized cellular XIAP and enhanced TNFα secretion. In the MDA-MB-231 xenograft model, administration of SM-164 at dose of 5 mg/kg markedly decreased cIAP-1 level within 1 hour and activated caspase-8, caspase-9 and caspase-3 at 3 hour 1.
    
    1. Lu J, Bai L, Sun H, et al. SM-164: a novel, bivalent Smac mimetic that induces apoptosis and tumor regression by concurrent removal of the blockade of cIAP-1/2 and XIAP. Cancer research, 2008, 68 (22): 9384-9393.
- Properties
  - Categories
    
    Anticancer agent
    
    CAS Number
    
    957135-43-2
    
    Molecular Formula
    
    C62H84N14O6
    
    Molecular Weight
    
    1121.42
    
    Purity
    
    98.04%
    
    Solubility
    
    ≥56.07 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
    
    Storage
    
    Store at -20°C
    
    SMILES
    
    O=C([[email protected]]1N(C([[email protected]@H](NC([[email protected]](C)NC)=O)CCCC2)=O)[[email protected]]2([H])CC1)N[[email protected]](C3=CN(CCCCC4=CC=C(CCCCN5C=C([[email protected]](NC([[email protected]@H]6CC[[email protected]](CCCC[[email protected]@H]7NC([[email protected]@H](NC)C)=O)([H])N6C7=O)=O)C8=CC=CC=C8)N=N5)C=C4)N=N3)C9=CC=CC=C9
    
    * For Research Use Only
- Reference
  - 1. Binghua Liu, Weiyan Wang, et al. "Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells." Cell Death Dis. 2021 Mar 3;12(3):230. PMID:33658488
    2. Miles MA, Caruso S, et al. "Smac mimetics can provoke lytic cell death that is neither apoptotic nor necroptotic." Apoptosis. 2020;10.1007/s10495-020-01610-8. PMID:32440848
    3. Lei W, Duan R, et al. "The IAP Antagonist SM-164 Eliminates Triple-Negative Breast Cancer Metastasis to Bone and Lung in Mice." Sci Rep. 2020;10(1):7004. PMID:32332865
    4. Mario G. Hollomon, LaNisha Patterson, et al. "Knockdown of Fas-Associated Protein withDeath Domain (FADD) Sensitizes Osteosarcoma to TNFα-induced Cell Death." Journal of Cancer.2019.
    5. Heidegger S, Wintges A, et al. "RIG-I activation is critical for responsiveness to checkpoint blockade." Sci Immunol. 2019 Sep 13;4(39). pii: eaau8943. PMID:31519811
    6. Hendrika W. Grievink, Jules A. A. C. Heuberger, et al. "DNL104, a centrally penetrant RIPK1 inhibitor, inhibits RIP1 kinase phosphorylation in a randomized phase I ascending dose study in healthy volunteers." Clinical Pharmacology & Therapeutics. 22 August 2019.
    7. Alexander F. G. Wintges. "Tumor immunosurveiliance: Innate immune activation as a mechanistic prerequisite for efficient immune checkpoint blockade in cancer immunotherapy." d-nb.info. 2018.
    8. Saleh D, Degterev A. "Chemical Library Screens to Identify Pharmacological Modulators of Necroptosis." Methods Mol Biol. 2018;1857:19-33. PMID:30136227
    9. Hao Q, Tang H. "Interferon-γ and Smac mimetics synergize to induce apoptosis of lung cancer cells in a TNFα-independent manner." Cancer Cell Int. 2018 Jun 14;18:84. PMID:29946223
    10. Gavin C. Sampey, David M. Irlbeck, et al. "The SMAC Mimetic AZD5582 is a Potent HIV Latency Reversing Agent" bioRxiv.2018.May 2.
    11. Sarhan J, Liu BC, et al. "Constitutive interferon signaling maintains critical threshold of MLKL expression to license necroptosis." Cell Death Differ. 2018 May 21. PMID:29786074
    12. Yang Z, Wang Y, et al. "RIP3 targets pyruvate dehydrogenase complex to increase aerobic respiration in TNF-induced necroptosis." Nat Cell Biol. 2018 Feb;20(2):186-197. PMID:29358703
    13. Chen X, He WT, et al."Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis." Cell Res. 2016 Sep;26(9):1007-20. PMID:27573174
    14. Shekhar TM, Miles MA, et al."IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα."Oncotarget. 2016 Jun 7;7(23):33866-86. PMID:27129149

Documents

COA (Certificate Of Analysis)

HPLC

NMR (Nuclear Magnetic Resonance)

MSDS (Material Safety Data Sheet)

Datasheet

SM-164

Background

Documents

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