Home Apoptosis IAP antagonist - HIV inhibitor - Apoptosis related activator Birinapant For research use only.

Birinapant

Synonyms: TL32711

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.

Birinapant Chemical Structure

Birinapant Chemical Structure

CAS No. 1260251-31-7

Purity & Quality Control

Products often used together with Birinapant

Zosuquidar 3HCl

Birinapant and Zosuquidar combination induces death of HBV-positive liver cells and improves HBV surface antigen (HBsAg) control kinetics in an immunocompetent mouse model of HBV infection.

Morrish E, et al. Viruses. 2020 Aug 17;12(8):901.

Birinapant Related Products

Signaling Pathway

IAP Signaling Pathways

IAP Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PANC-1 Growth Inhibition Assay 50/200/500 nM 0-96 h inhibits cell growth in both time and dose dependent manner 26252969
Molm13  Function Assay 2/20/200 nM 24 h decreases cIAP1 and, to a much lesser extent, cIAP2, and XIAP under various conditions 24526787
WTH202 Growth Inhibition Assay 72 h IC50=1.8 nM, combined with 1ng/ml TNF-α 23403634
WM793B Growth Inhibition Assay 72 h IC50=2.5 nM, combined with 1ng/ml TNF-α 23403634
WM9 Growth Inhibition Assay 72 h IC50=2.4 nM 23403634
WM9 Growth Inhibition Assay 72 h IC50=2.7 nM, combined with 1ng/ml TNF-α 23403634
WM1366 Growth Inhibition Assay 72 h IC50=7.9 nM, combined with 1ng/ml TNF-α 23403634
WM164 Growth Inhibition Assay 72 h IC50=9 nM, combined with 1ng/ml TNF-α 23403634
451Lu Growth Inhibition Assay 72 h IC50=14.2 nM, combined with 1ng/ml TNF-α 23403634
WM1341D Growth Inhibition Assay 72 h IC50=57.6 nM, combined with 1ng/ml TNF-α 23403634
WM3130 Growth Inhibition Assay 72 h IC50=64.3 nM, combined with 1ng/ml TNF-α 23403634
WM1985 Growth Inhibition Assay 72 h IC50=97 nM, combined with 1ng/ml TNF-α 23403634
WM3854 Growth Inhibition Assay 72 h IC50=226 nM, combined with 1ng/ml TNF-α 23403634
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against cIAP/XIAP-dependent human MDA-MB-231 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.01 μM. 25584393
A875 Cytotoxicity assay 72 hrs Cytotoxicity against XIAP-dependent human A875 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.04 μM. 25584393
Click to View More Cell Line Experimental Data

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
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]
Kinase Assay 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 Research 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
Experimental Result Images Methods Biomarkers Images PMID
Western blot cIAP1 / cIAP2 / XIAP NF-κB(p65) / IκBa / Bcl-xl / NF-κB(p100) / p52 BIRC2 / ARC 24526787
Immunofluorescence Caspase 3/7 28665401
Growth inhibition assay Cell viability 28460471
In Vivo
In vivo Birinapant (30 mg/kg) treatment significantly induces abrogation of tumor growth in melanoma xenotransplantation models 451Lu with. [2]
Animal Research Animal Models Human melanoma xenografts 451Lu
Dosages 30 mg/kg
Administration 3 times per week intraperitoneally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01681368 Terminated
Epithelial Ovarian Cancer|Peritoneal Neoplasms|Fallopian Tube Neoplasms
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 August 15 2012 Phase 2
NCT01486784 Terminated
Acute Myelogenous Leukemia
Abramson Cancer Center at Penn Medicine
 November 2011 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 806.94 Formula

C42H56F2N8O6
CAS No. 1260251-31-7 SDF Download Birinapant SDF
Smiles CCC(C(=O)N1CC(CC1CC2=C(NC3=C2C=CC(=C3)F)C4=C(C5=C(N4)C=C(C=C5)F)CC6CC(CN6C(=O)C(CC)NC(=O)C(C)NC)O)O)NC(=O)C(C)NC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (123.92 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 55 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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