Birinapant

Catalog No.S7015 Batch:S701502

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Technical Data

Formula

C42H56F2N8O6
Molecular Weight 806.94 CAS No. 1260251-31-7
Solubility (25°C)* In vitro DMSO 100 mg/mL (123.92 mM)
Ethanol 100 mg/mL (123.92 mM)
Water Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
cIAP1 [1]
(Cell-free assay)		 XIAP [1]
(Cell-free assay)
<1 nM(Kd) 45 nM(Kd)
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[2]
  • Cell lines

    Human melanoma cell lines WM9

  • Concentrations

    1 nM-1 μM

  • Incubation Time

    3 days

  • Method

    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
Animal Study:[2]
  • Animal Models

    Human melanoma xenografts 451Lu

  • Dosages

    30 mg/kg

  • Administration

    3 times per week intraperitoneally

Customer Product Validation

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.]

Data from [Data independently produced by , , Cell Death Dis, 2017, 8(1):e2535]

Selleck's Birinapant has been cited by 77 publications

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
Caspase 8 protects pancreatic neoplasia from KRAS-driven necroptotic priming [ Research Square, 2023, Version 2] PubMed: none
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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