Birinapantfeatured
WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#:205645
CAS#:1260251-31-7
Description:Birinapant, also known as TL32711, is a synthetic small molecule and peptido mimetic of second mitochondrial-derived activator of caspases (SMAC) and inhibitor of IAP (Inhibitor of Apoptosis Protein) family proteins, with potential antineoplastic activity. As a SMAC mimetic and IAP antagonist, TL32711 binds to and inhibits the activity of IAPs, such as X chromosome-linked IAP (XIAP) and cellular IAPs 1 and 2.
Price and Availability
Birinapant (TL32711)is in stock.
Chemical Structure
Theoretical Analysis
MedKoo Cat#: 205645Name: BirinapantCAS#: 1260251-31-7Chemical Formula: C42H56F2N8O6Exact Mass: 806.42909Molecular Weight: 806.94Elemental Analysis:C, 62.51; H, 6.99; F, 4.71; N, 13.89; O, 11.90
Synonym:TL32711; TL-32711; TL 32711; SMAC mimetic; Birinapant
IUPAC/Chemical Name:(2S)-N-[(2S)-1-[(2R,4S)-2-[[6-fluoro-2-[6-fluoro-3-[[(2R,4S)-4-hydroxy-1-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]pyrrolidin-2-yl]methyl]-1H-indol-2-yl]-1H-indol-3-yl]methyl]-4-hydroxypyrrolidin-1-yl]-1-oxobutan-2-yl]-2-(methylamino)propanamide
InChi Key:PKWRMUKBEYJEIX-DXXQBUJASA-N
InChi Code:InChI=1S/C42H56F2N8O6/c1-7-33(49-39(55)21(3)45-5)41(57)51-19-27(53)15-25(51)17-31-29-11-9-23(43)13-35(29)47-37(31)38-32(30-12-10-24(44)14-36(30)48-38)18-26-16-28(54)20-52(26)42(58)34(8-2)50-40(56)22(4)46-6/h9-14,21-22,25-28,33-34,45-48,53-54H,7-8,15-20H2,1-6H3,(H,49,55)(H,50,56)/t21-,22-,25-,26-,27-,28-,33-,34-/m0/s1
SMILES Code:C[C@H](NC)C(N[C@@H](CC)C(N1[C@H](CC2=C(C(N3)=C(C[C@H]4N(C([C@@H](NC([C@@H](NC)C)=O)CC)=O)C[C@@H](O)C4)C5=C3C=C(F)C=C5)NC6=C2C=CC(F)=C6)C[C@H](O)C1)=O)=O
Technical Data
Additional Information
In Phase 1 clinical studies as a single agent and in combination with standard-of-care chemotherapies, TL32711 has demonstrated strong correlation between drug exposure, target coverage and apoptosis induction in tumors at well-tolerated doses as well as promising anti-tumor activity in patients. TL32711 is entering Phase 2 single agent and combination clinical studies in solid tumors and a Phase 1/2 clinical study in acute myeloid leukemia. TetraLogic will execute a Phase 2 clinical program to explore the broad therapeutic potential of Smac mimetics with the support of substantial non-dilutive funding that reduces downstream equity requirements. (source: http://www.tetralogicpharma.com/research_tl32711.html).
References
1: Elsawy MA, Tikhonova IG, Martin SL, Walker B. Smac-derived Aza-peptide As an Aminopeptidase-resistant XIAP BIR3 Antagonist. Protein Pept Lett. 2015 Jun 21. [Epub ahead of print] PubMed PMID: 26095377.
2: Ebert G, Allison C, Preston S, Cooney J, Toe JG, Stutz MD, Ojaimi S, Baschuk N, Nachbur U, Torresi J, Silke J, Begley CG, Pellegrini M. Eliminating hepatitisB by antagonizing cellular inhibitors of apoptosis. Proc Natl Acad Sci U S A. 2015 May 5;112(18):5803-8. doi: 10.1073/pnas.1502400112. Epub 2015 Apr 20. PubMed PMID: 25902530; PubMed Central PMCID: PMC4426438.
3: Papaevangelou E, Almeida GS, Jamin Y, Robinson SP, deSouza NM. Diffusion-weighted MRI for imaging cell death after cytotoxic or apoptosis-inducing therapy. Br J Cancer. 2015 Apr 28;112(9):1471-9. doi: 10.1038/bjc.2015.134. Epub 2015 Apr 16. PubMed PMID: 25880014; PubMed Central PMCID: PMC4453679.
4: Brady SW, Zhang J, Tsai MH, Yu D. PI3K-independent mTOR activation promotes lapatinib resistance and IAP expression that can be effectively reversed by mTORand Hsp90 inhibition. Cancer Biol Ther. 2015;16(3):402-11. doi: 10.1080/15384047.2014.1002693. PubMed PMID: 25692408.
5: Lee EW, Seong D, Seo J, Jeong M, Lee HK, Song J. USP11-dependent selective cIAP2 deubiquitylation and stabilization determine sensitivity to Smac mimetics.Cell Death Differ. 2015 Jan 23. doi: 10.1038/cdd.2014.234. [Epub ahead of print]PubMed PMID: 25613375.
6: Eytan DF, Snow GE, Carlson SG, Schiltz S, Chen Z, Van Waes C. Combination effects of SMAC mimetic birinapant with TNFα, TRAIL, and docetaxel in preclinical models of HNSCC. Laryngoscope. 2015 Mar;125(3):E118-24. doi: 10.1002/lary.25056.Epub 2014 Nov 28. PubMed PMID: 25431358; PubMed Central PMCID: PMC4336212.
7: Mak PY, Mak DH, Ruvolo V, Jacamo R, Kornblau SM, Kantarjian H, Andreeff M, Carter BZ. Apoptosis repressor with caspase recruitment domain modulates second mitochondrial-derived activator of caspases mimetic-induced cell death through BIRC2/MAP3K14 signalling in acute myeloid leukaemia. Br J Haematol. 2014 Nov;167(3):376-84. doi: 10.1111/bjh.13054. Epub 2014 Jul 31. PubMed PMID: 25079338; PubMed Central PMCID: PMC4357400.
8: Condon SM, Mitsuuchi Y, Deng Y, LaPorte MG, Rippin SR, Haimowitz T, AlexanderMD, Kumar PT, Hendi MS, Lee YH, Benetatos CA, Yu G, Kapoor GS, Neiman E, Seipel ME, Burns JM, Graham MA, McKinlay MA, Li X, Wang J, Shi Y, Feltham R, Bettjeman B, Cumming MH, Vince JE, Khan N, Silke J, Day CL, Chunduru SK. Birinapant, a smac-mimetic with improved tolerability for the treatment of solid tumors and hematological malignancies. J Med Chem. 2014 May 8;57(9):3666-77. doi: 10.1021/jm500176w. Epub 2014 Apr 15. PubMed PMID: 24684347.
9: Benetatos CA, Mitsuuchi Y, Burns JM, Neiman EM, Condon SM, Yu G, Seipel ME, Kapoor GS, Laporte MG, Rippin SR, Deng Y, Hendi MS, Tirunahari PK, Lee YH, Haimowitz T, Alexander MD, Graham MA, Weng D, Shi Y, McKinlay MA, Chunduru SK. 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. doi: 10.1158/1535-7163.MCT-13-0798. Epub 2014 Feb 21. Erratum in: Mol Cancer Ther. 2014 Sep;13(9):2246-7. Dosage error in article text. PubMed PMID: 24563541.
10: Carter BZ, Mak PY, Mak DH, Shi Y, Qiu Y, Bogenberger JM, Mu H, Tibes R, Yao H, Coombes KR, Jacamo RO, McQueen T, Kornblau SM, Andreeff M. Synergistic targeting of AML stem/progenitor cells with IAP antagonist birinapant and demethylating agents. J Natl Cancer Inst. 2014 Feb;106(2):djt440. doi: 10.1093/jnci/djt440. PubMed PMID: 24526787; PubMed Central PMCID: PMC3952202.
MedKoo,由化学家和药学家陈清奇博士。北卡罗莱纳州的研究三角区(ResearchTrianglePark,简称RTP),是一家以研发、生产和销售小分子抗癌化合物为主的医药科技公司,该公司的业务范围主要是为全球所有从事抗癌药物研究和开发的制药公司,高校,研究院所,政府相关机构提供与抗癌药物分子相关的产品、试剂和技术服务。
中文名MedKoo中 文美帝药库医药科技公司创立于2008年总部位于美国东海岸
MedKoo是世界领先的供应商之一的抗癌化学试剂和激酶抑制剂。我们制造、销售和分发高质量的抗癌小分子肿瘤学研究试剂。我们的使命是建立世界上最全面的抗癌小分子的集合。我们也为医药行业提供高质量的研究服务、医学研究机构和学术机构。我们致力于提供优质的服务。 MedKoo是世界领先的供应商之一的抗癌化学试剂和激酶抑制剂。我们制造、销售和分发高质量的抗癌小分子肿瘤学研究试剂。我们的使命是建立世界上最全面的抗癌小分子的集合。我们也为医药行业提供高质量的研究服务、医学研究机构和学术机构。我们致力于提供优质的服务和分子有竞争力的价格。MedKoo是您可靠的合作伙伴采购药物发现和药物分子。 MedKoo是世界的抗癌化学试剂和激酶抑制剂供应商之一。我们制造,销售和分销用于肿瘤学研究的高质量抗癌小分子试剂。我们的使命是建立世界上全面的抗癌小分子集合。我们还为制药行业,医学研究组织和学术机构提供高质量的研究服务。我们致力于以具有竞争力的价格提供服务和分子。MedKoo是您可靠的药物发现和药物分子采购合作伙伴。 CRISPR-Cas9是近年兴起的用于靶向基因组特定位置,进行DNA修饰的重要工具。研究发现CRISPR是细菌为了应对病毒的攻击而演化而来的获得性免疫防御机制。具体来说,在CRISPR和Cas9的作用下,经由小RNA分子的引导,靶向并沉默入侵者遗传物质核酸的关键部分。在该系统中,crRNA(CRISPR-derivedRNA)与tracrRNA(trans-activatingRNA)结合形成的复合物能特异性识别靶基因序列,并引导Cas9核酸内切酶在靶定位点剪切双链DNA,随后,细胞的非同源末端连接修复机制(NHEJ)重新连接断裂处的基因组DNA,并引入插入或缺失突变。另外也可以提供一个外源双链供体DNA(Donor)通过同源重组(HR)整合进断裂处的基因组,从而达到对基因组DNA进行修饰的目的。
目前,CRISPR-Cas9系统的高效基因组编辑功能已被应用于多种生物,包括小鼠、大鼠、斑马鱼、秀丽隐杆线虫,也包含多种细菌和植物,甚至在人体上也有应用。
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