1. Apoptosis
  2. IAP

Birinapant (Synonyms: TL32711)

Cat. No.: HY-16591 Purity: 99.84%
Data Sheet SDS Handling Instructions

Birinapant a bivalent Smac mimetic, is a potent antagonist for XIAP and cIAP1 with Kd values of 45 nM and < 1 nM, respectively.

For research use only. We do not sell to patients.
Birinapant Chemical Structure

Birinapant Chemical Structure

CAS No. : 1260251-31-7

Size Price Stock Quantity
10 mM * 1 mL in DMSO $107 In-stock
5 mg $70 In-stock
10 mg $120 In-stock
50 mg $280 In-stock
100 mg $500 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Technical Information

  • Purity & Documentation

  • References

Description

Birinapant a bivalent Smac mimetic, is a potent antagonist for XIAP and cIAP1 with Kd values of 45 nM and < 1 nM, respectively.

IC50 & Target

Kd: 45 nM (XIAP), <1 nM (cIAP1)

In Vitro

Birinapant causes significant degradation of cIAP1 and 2. Birinapant + TRAIL-treated cells show increased levels of active caspase-8 and caspase-3, as well as PARP cleavage, over single agents within 4 h of treatment, indicative of apoptosis-mediated cell death. Birinapan significantly decreases the viability of SUM190 cells in a dose-dependent manner. Birinapant treatment in the XIAP knockdown cell line (SUM190 shXIAP) causes an overall reduction in viability at lower doses (30-300 nM)[1]. Birinapant causes apoptosis in the sensitive cells. Birinapant in conbination with TNF-α, causes PARP cleavage in 451Lu and WM1366 cell lines[2]. Birinapant induces time-course of caspase-3 activation in HCT116 human colon carcinoma and MDA-MB-231 human breast adenocarcinoma cells[3].

In Vivo

Birinapant can inhibit tumor growth in melanoma xenotransplantation models. Staining for activated caspase-3 in biopsies of the same tumors show a modest increase in apoptotic cells in the birinapant treated animals[2]. Birinapant (15 mg/kg, i.p.) induces apoptosis in HCT116 tumor-bearing mouse[3].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02587962 TetraLogic Pharmaceuticals|Merck Sharp & Dohme Corp. Solid Tumors February 2017 Phase 1|Phase 2
NCT02147873 TetraLogic Pharmaceuticals Myelodysplastic Syndrome (MDS)|Chronic Myelomonocytic Leukemia (CMML) June 2014 Phase 2
NCT01940172 TetraLogic Pharmaceuticals Relapsed Epithelial Ovarian Cancer|Relapsed Primary Peritoneal Cancer|Relapsed Fallopian Tube Cancer November 2013 Phase 1
NCT01828346 TetraLogic Pharmaceuticals Myelodysplastic Syndrome June 2013 Phase 1|Phase 2
NCT01188499 TetraLogic Pharmaceuticals Cancer October 2010 Phase 1|Phase 2
NCT02288208 TetraLogic Pharmaceuticals Hepatitis B November 2014 Phase 1
NCT01681368 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Epithelial Ovarian Cancer|Peritoneal Neoplasms|Fallopian Tube Neoplasms August 15, 2012 Phase 2
NCT02756130 Jonsson Comprehensive Cancer Center|TetraLogic Pharmaceuticals Advanced Newly Diagnosed or Recurrent High Grade Serous Carcinomas (HGSC) January 2017 Phase 2
NCT00993239 TetraLogic Pharmaceuticals Cancer November 2009 Phase 1
NCT02587962 TetraLogic Pharmaceuticals|Merck Sharp & Dohme Corp. Solid Tumors February 2017 Phase 1|Phase 2
NCT02147873 TetraLogic Pharmaceuticals Myelodysplastic Syndrome (MDS)|Chronic Myelomonocytic Leukemia (CMML) June 2014 Phase 2
NCT01940172 TetraLogic Pharmaceuticals Relapsed Epithelial Ovarian Cancer|Relapsed Primary Peritoneal Cancer|Relapsed Fallopian Tube Cancer November 2013 Phase 1
NCT01828346 TetraLogic Pharmaceuticals Myelodysplastic Syndrome June 2013 Phase 1|Phase 2
NCT01188499 TetraLogic Pharmaceuticals Cancer October 2010 Phase 1|Phase 2
NCT02288208 TetraLogic Pharmaceuticals Hepatitis B November 2014 Phase 1
NCT01681368 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Epithelial Ovarian Cancer|Peritoneal Neoplasms|Fallopian Tube Neoplasms August 15, 2012 Phase 2
NCT02756130 Jonsson Comprehensive Cancer Center|TetraLogic Pharmaceuticals Advanced Newly Diagnosed or Recurrent High Grade Serous Carcinomas (HGSC) January 2017 Phase 2
NCT00993239 TetraLogic Pharmaceuticals Cancer November 2009 Phase 1
NCT01573780 Roswell Park Cancer Institute|National Cancer Institute (NCI)|TetraLogic Pharmaceuticals Unspecified Adult Solid Tumor, Protocol Specific April 2012 Phase 1
NCT01486784 Abramson Cancer Center of the University of Pennsylvania Acute Myelogenous Leukemia November 2011 Phase 1|Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.2392 mL 6.1962 mL 12.3925 mL
5 mM 0.2478 mL 1.2392 mL 2.4785 mL
10 mM 0.1239 mL 0.6196 mL 1.2392 mL
Cell Assay
[1]

Trypan blue exclusion assay is performed as described. Cells are seeded in 6 well plates at 7.5×104 (SUM149) or 1.5×105 (SUM190) cells per well and allowed to adhere overnight. Cells are treated with TRAIL (0-100 ng/mL), Birinapant (0-10,000 nM), GT13402 (0-10,000 nM), TNF-α (50 ng/mL), TNF-α neutralizing antibody (10 μg/mL), pan-caspase inhibitor Q-VD-OPh (20 μM), or a combination as indicated. All treatments are applied for 24 h, and then the cells are trypsinized and resuspended in PBS. Next, 10 μL of cell suspension is added to 10 μL 0.4 % trypan blue, and 10 μL of the mixture is loaded onto a hemocytometer; cells are counted, and live and dead cell numbers are recorded. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Birinapant is dissolved in 12.5% Captisol in distilled water.

Ten animals each are inoculated s.c. with 1×106 451Lu or 1205Lu human melanoma cells in a suspension of matrigel/complete media at a ratio of 1:1. After formation of palpable tumors, mice from both tumor models are randomized into two groups. Both groups are treated intraperitoneal three times/week with either vehicle control or birinapant 30 mg/kg for 21 days. Birinapant is dissolved in 12.5% Captisol in distilled water. Tumor size is assessed twice weekly by caliper measurement. Subsequently, satellite groups of ten and fifteen mice are inoculated in the same fashion with 451Lu and 1205Lu tumor cells respectively. After tumors have reached a mean volume of 200 mm3 animals are dosed with either birinapant or vehicle control as described above. After 48 hours and two doses, animals are sacrificed and tumors are harvested at four time points after the last treatment. Tumor samples are snap frozen in liquid nitrogen for subsequent protein analysis and preserved as FFPE blocks for immune-histochemistry. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

806.94

Formula

C₄₂H₅₆F₂N₈O₆

CAS No.

1260251-31-7

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 40 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.84%

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Product Name:
Birinapant
Cat. No.:
HY-16591
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