[CAS NO. 1260251-31-7] Birinapant
PRODUCTS SPECIFICATIONS [1260251-31-7]
DESCRIPTION [1260251-31-7]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 806.94 |
| Molecular Formula | C42H56F2N8O6 |
| SMILES | FC1=CC2=C(C=C1)C(C[C@H]3N(C([C@@H](NC([C@@H](NC)C)=O)CC)=O)C[C@@H](O)C3)=C(C(N4)=C(C[C@H]5N(C([C@@H](NC([C@@H](NC)C)=O)CC)=O)C[C@@H](O)C5)C6=C4C=C(F)C=C6)N2 |
18 Publications Citing Use of MCE
- [1]Cell. 2019 Jul 25;178(3):585-599.e15.
- [2]Cell Death Differ. 2021 Oct;28(10):2888-2899.
- [3]Dev Cell. 2019 Oct 21;51(2):277-291.e4.
- [4]Oncogene. 2022 Jun 9.
- [5]Cell Death Dis. 2021 Jun 23;12(7):641.
- [6]Cell Death Dis. 2020 Feb 5;11(2):94.
- [7]Cancers (Basel). 2022 Mar 19;14(6):1575.
- [8]Cell Oncol (Dordr). 2019 Jun;42(3):319-329.
- [9]J Cell Mol Med. 2021 May 3;25(13):6125-6136.
- [10]Front Microbiol. 2018 Sep 19;9:2022.
- [11]Mol Ther Oncolytics. 2022 Nov 15;27:288-304.
- [12]Mol Ther Oncolytics. 2022.
- [13]Aquaculture. 2021, 736595.
- [14]Mol Med Rep. 2020 Mar;21(3):1251-1257.
- [15]University of Portland. Department of Biology
- [16]Patent. US20210269505A1.
- [17]bioRxiv. 2019 Nov.
- [18]University Regensburg. 2017 Jul.
Summary
Birinapant (TL32711), a bivalent Smac mimetic, is a potent antagonist for XIAP and cIAP1 with K d s of 45 nM and less than 1 nM, respectively. Birinapant (TL32711) induces the autoubiquitylation and proteasomal degradation of cIAP1 and cIAP2 in intact cells, which results in formation of a RIPK1: caspase-8 complex, caspase-8 activation, and induction of tumor cell death. Birinapant (TL32711) targets TRAF2-associated cIAPs and abrogates TNF-induced NF-κB activation.
IC50 & Target
Kd: 45 nM (XIAP), <1 nM (cIAP1) [1]
In Vitro
Birinapant (TL32711) (30-10000 nM; 24 hours) significantly decreases the viability of SUM190 cells in a dose-dependent manner
[1]
.
Birinapant (TL32711) (30-1000 nM; 4 hours) shows a significant decrease in cIAP1 levels and enhanced PARP cleavage, and induces apoptosis
[1]
.
Birinapant (TL32711) binds with high affinity to the isolated BIR3 domains of cIAP1, cIAP2, and XIAP and the single BIR domain of ML-IAP and rapidly degrades TRAF2-bound cIAP1 and cIAP2 thereby inhibiting TNF-mediated NF-κB activation
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| Cell Line: | TRAIL-resistant SUM190 IBC cells |
| Concentration: | 30, 100, 300, 1000, 10000 nM |
| Incubation Time: | 24 hours |
| Result: | Significantly decreased the viability of SUM190 cells in a dose-dependent manner. |
Western Blot Analysis [1]
| Cell Line: | SUM190 cells |
| Concentration: | 30, 300, 1000 nM |
| Incubation Time: | 4 hours |
| Result: | Showed a significant decrease in cIAP1 levels and enhanced PARP cleavage. |
In Vivo
Birinapant (TL32711) (30 mg/kg; i.p.; every third day (*5)) shows antitumor efficacy and are devoid of overt toxicity in preclinical models [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female athymic nude mice (low-passage, patient-derived xenotransplant models of ovarian cancer, colorectal cancer, and melanoma) [2] |
| Dosage: | 30 mg/kg |
| Administration: | Intraperitoneal injection; every third day (*5) |
| Result: | Resulted in inhibition of tumor growth. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02756130 | Jonsson Comprehensive Cancer Center|Alpha Stem Cell Clinic (ASCC)|California Institute for Regenerative Medicine (CIRM)|TetraLogic Pharmaceuticals |
High Grade Fallopian Tube Serous Adenocarcinoma|High Grade Ovarian Serous Adenocarcinoma|Primary Peritoneal High Grade Serous Adenocarcinoma|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma
|
August 1, 2018 | Phase 1|Phase 2 |
| NCT04553692 | IGM Biosciences, Inc. |
Solid Tumor|Colorectal Cancer|Non Hodgkin Lymphoma|Sarcoma|Chondrosarcoma|Small Lymphocytic Lymphoma|Chronic Lymphocytic Leukemia|Acute Myeloid Leukemia
|
September 23, 2020 | Phase 1 |
| NCT02288208 | TetraLogic Pharmaceuticals |
Hepatitis B
|
November 2014 | Phase 1 |
| NCT01188499 | TetraLogic Pharmaceuticals |
Cancer
|
October 2010 | Phase 1|Phase 2 |
| NCT03803774 | National Cancer Institute (NCI) |
Locally Recurrent Head and Neck Squamous Cell Carcinoma|Nasopharyngeal Squamous Cell Carcinoma|Sinonasal Squamous Cell Carcinoma
|
January 7, 2019 | Phase 1 |
| NCT01940172 | TetraLogic Pharmaceuticals |
Relapsed Epithelial Ovarian Cancer|Relapsed Primary Peritoneal Cancer|Relapsed Fallopian Tube Cancer
|
November 2013 | Phase 1 |
| NCT00993239 | TetraLogic Pharmaceuticals |
Cancer
|
November 2009 | Phase 1 |
| NCT01486784 | Abramson Cancer Center of the University of Pennsylvania |
Acute Myelogenous Leukemia
|
November 2011 | Phase 1|Phase 2 |
| NCT02147873 | TetraLogic Pharmaceuticals |
Myelodysplastic Syndrome (MDS)|Chronic Myelomonocytic Leukemia (CMML)
|
June 2014 | Phase 2 |
| NCT01828346 | TetraLogic Pharmaceuticals |
Myelodysplastic Syndrome
|
June 2013 | Phase 1|Phase 2 |
| NCT01573780 | Roswell Park Cancer Institute|TetraLogic Pharmaceuticals |
Unspecified Adult Solid Tumor, Protocol Specific
|
April 2012 | 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 |
| NCT02587962 | Medivir|Merck Sharp & Dohme LLC |
Solid Tumors
|
August 4, 2017 | Phase 1|Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 125 mg/mL ( 154.91 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent 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 |
References
- [1] Allensworth JL, et al. Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism. Breast Cancer Res Treat. 2013 Jan;137(2):359-71.
- [2] Krepler C, et al. The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells. Clin Cancer Res. 2013 Apr 1;19(7):1784-94.
- [3] Nguyen QD, et al. Temporal and spatial evolution of therapy-induced tumor apoptosis detected by caspase-3-selective molecular imaging. Clin Cancer Res. 2013 Jul 15;19(14):3914-24.
- [4] Benetatos CA, et al. Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-κB activation, and is active in patient-derived xenograft models. Mol Cancer Ther. 2014 Apr;13(4):867-79.