Birinapant

製品コードS7015 バッチS701503

印刷

化学情報

Chemical Structure Synonyms TL32711 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C42H56F2N8O6
分子量 806.94 CAS No. 1260251-31-7
Solubility (25°C)* 体外 DMSO 100 mg/mL (123.92 mM)
Ethanol 13 mg/mL (16.11 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5% DMSO 95% Corn oil
0.6mg/ml Taking the 1 mL working solution as an example, add 50 μL of 12 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
6.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 120 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Birinapant is a SMAC mimetic antagonist, mostly to cIAP1 with Kd of <1 nM in a cell-free assay, less potent to XIAP. Birinapant helps to induce apoptosis in latent HIV-1-infected cells. Phase 2.
in vitro Birinapant binds with XIAP and cIAP1 with Kd of 45 and <1 nM, respectively. Birinapant induces cell death as a single agent in TRAIL-insensitive SUM190 (ErbB2-overexpressing) cells (IC50, ~300 nM), and significantly increases potency of TRAIL-induced apoptosis in TRAIL-sensitive SUM149 (triple-negative, EGFR-activated) cells. Birinapant causes rapid cIAP1 degradation, caspase activation, PARP cleavage, and NF-κB activation. [1] Birinapant in combination with TNF-α exhibits a strong antimelanoma effect in vitro. Birinapant in combination with TNF-α(1 ng/mL) inhibits the growth of human melanoma cell lines WTH202, WM793B, WM1366 and WM164 with IC50s of 1.8, 2.5, 7.9 and 9 nM, respectively, while neither compound is effective individually. Birinapant singly treatment induces inhibition on proliferation of WM9 cells with IC50 of 2.4 nM. Birinapant significantly inhibits the target protein cIAP1 and cIAP2 in these cell lines.[2]
in vivo Birinapant (30 mg/kg) treatment significantly induces abrogation of tumor growth in melanoma xenotransplantation models 451Lu with. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Fluorescence polarization assay
The binding affinities of compounds to XIAP and cIAP1 are determined using a fluorogenic substrate and are reported as Kd values. Initially, the dissociation constant (Kd) for the fluorescently labeled modified Smac peptide (AbuRPF-K(5-Fam)-NH2; FP pep-tide) is determined using a fixed concentration of peptide (5 nM) and titrating varying concentrations of protein (0.075–5 μM in half log dilutions). The dose–response curves are produced by a nonlinear least squares fit to a single-site binding model using GraphPad Prism, with 5 nM of FP peptide and 50 nM of XIAP used in the assay. Various concentrations of Smac mimetics (100–0.001 μM in half log dilutions) are added to FP peptide:protein binary complex for 15 min at room temperature in 100μL of 0.1 M potassium phosphate buffer, pH 7.5, containing 100 mg/mL bovine c -globulin. Following incubation, the polarization values are measured on a multi-label plate reader using a 485 nm excitation filter and a 520 nm emission filter.
細胞アッセイ 細胞株 Human melanoma cell lines WM9
濃度 1 nM-1 μM
反応時間 3 days
実験の流れ Cells are allowed to attach for 24 hours and subsequently incubated with Birinapant and/or TNF-α for 24 or 72 hours. Then MTS assay is conducted
動物実験 動物モデル Human melanoma xenografts 451Lu
投薬量 30 mg/kg
投与方法 3 times per week intraperitoneally

カスタマーフィードバック

Data from [Cell Death Dis, 2013, 4, e951]

Data from [Data independently produced by , , British Journal of Cancer, 2015, 112: 1471–1479]

Data from [Data independently produced by , , Cell Death Differ, 2016, 23(10):1628-37.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL [ Cell Death Dis, 2024, 15(1):77] PubMed: 38245534
A RIPK3-independent role of MLKL in suppressing parthanatos promotes immune evasion in hepatocellular carcinoma [ Cell Discov, 2023, 9(1):7] PubMed: 36650126
Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer [ Cancer Res, 2023, 83(19):3284-3304] PubMed: 37450351
FAP is critical for ovarian cancer cell survival by sustaining NF-κB activation through recruitment of PRKDC in lipid rafts [ Cancer Gene Ther, 2023, 30(4):608-621] PubMed: 36494579
The centrosomal protein 131 participates in the regulation of mitochondrial apoptosis [ Commun Biol, 2023, 6(1):1271] PubMed: 38102401
Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer [ Heliyon, 2023, 9(10):e20655] PubMed: 37867861
Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer [ Heliyon, 2023, 9(10):e20655] PubMed: 37867861
CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects [ Sci Adv, 2023, 9(33):eadf6692] PubMed: 37595047
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Caspase-8 has dual roles in regulatory T cell homeostasis balancing immunity to infection and collateral inflammatory damage [ Sci Immunol, 2022, 7(69):eabn8041] PubMed: 35333545

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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