Marimastat (BB-2516)

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WARNING: This product is for research use only, not for human or veterinary use.

Description:Marimastat, aslo known as BB-2516 and TA-2516, is an orally-active synthetic hydroxamateand inhibitor of matrix metalloproteinases with potential antineoplastic activity. Marimastat covalently binds to the zinc(II) ion in the active site of matrix metalloproteinases (MMPs), thereby inhibiting the action of MMPs, inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. This agent may also inhibit tumor necrosis factor-alpha converting enzyme (TACE), an enzyme involved in tumor necrosis factor alpha (TNF-alpha) production that may play a role in some malignancies as well as in the development of arthritis and sepsis.

Price and Availability

Marimastat (BB-2516) is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 201802Name: Marimastat (BB-2516)CAS#: 154039-60-8Chemical Formula: C15H29N3O5Exact Mass: 331.21072Molecular Weight: 331.41Elemental Analysis:C, 54.36; H, 8.82; N, 12.68; O, 24.14

Synonym:BB-2516; BB2516; BB 2516; TA-2516; TA2516; TA 2516;Marimastat.

IUPAC/Chemical Name:(2R,3S)-N1-((S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-N4,3-dihydroxy-2-isobutylsuccinamide

InChi Key:BSGICWROEOGEDW-UHFFFAOYSA-N

InChi Code:InChI=1S/C9H20Cl2N2O5PS2/c10-2-4-13(5-3-11)19(14)12-9(1-6-18-19)20-7-8-21(15,16)17/h9,12,19H,1-8H2,(H,15,16,17)/q-1

SMILES Code:O=C(N[C@@H](C(C)(C)C)C(NC)=O)[C@H](CC(C)C)[C@H](O)C(NO)=O

Technical Data

Additional Information

Acoording to wikipedia (http://en.wikipedia.org/wiki/Marimastat), Marimastat was a proposed antineoplastic drug developed by British Biotech. It acted as a broad-spectrum matrix metalloproteinase inhibitor. Marimastat performed poorly in clinical trials, and development was terminated

References

  1: Underwood C, Collins SN, van Eps AW, Mills PC, Allavena RE, Bailey SR, MedinaTorres CE, Meizler A, Pollitt CC. Intraosseous infusion of the distal phalanx compared to systemic intravenous infusion for marimastat delivery to equine lamellar tissue. Vet J. 2015 May 19. pii: S1090-0233(15)00216-6. doi: 10.1016/j.tvjl.2015.05.010. [Epub ahead of print] PubMed PMID: 26073286.

2: Underwood C, Collins SN, Mills PC, Van Eps AW, Allavena RE, Medina Torres CE,Pollitt CC. Regional intravenous limb perfusion compared to systemic intravenousadministration for marimastat delivery to equine lamellar tissue. J Vet Pharmacol Ther. 2015 Aug;38(4):392-9. doi: 10.1111/jvp.12198. Epub 2015 Jan 30. PubMed PMID: 25641095.

3: Yu M, Lim NH, Ellis S, Nagase H, Triccas JA, Rutledge PJ, Todd MH. Incorporation of Bulky and Cationic Cyclam-Triazole Moieties into Marimastat CanGenerate Potent MMP Inhibitory Activity without Inducing Cytotoxicity. ChemistryOpen. 2013 Jun;2(3):99-105. doi: 10.1002/open.201300014. Epub 2013 Jun 12. PubMed PMID: 24551546; PubMed Central PMCID: PMC3703814.

4: Sinno M, Biagioni S, Ajmone-Cat MA, Pafumi I, Caramanica P, Medda V, Tonti G,Minghetti L, Mannello F, Cacci E. The matrix metalloproteinase inhibitor marimastat promotes neural progenitor cell differentiation into neurons by gelatinase-independent TIMP-2-dependent mechanisms. Stem Cells Dev. 2013 Feb 1;22(3):345-58. doi: 10.1089/scd.2012.0299. Epub 2012 Dec 7. PubMed PMID: 23098139.

5: Lenger J, Kaschani F, Lenz T, Dalhoff C, Villamor JG, Köster H, Sewald N, vander Hoorn RA. Labeling and enrichment of Arabidopsis thaliana matrix metalloproteases using an active-site directed, marimastat-based photoreactive probe. Bioorg Med Chem. 2012 Jan 15;20(2):592-6. doi: 10.1016/j.bmc.2011.06.068.Epub 2011 Jun 29. PubMed PMID: 21775155.

6: auf dem Keller U, Bellac CL, Li Y, Lou Y, Lange PF, Ting R, Harwig C, Kappelhoff R, Dedhar S, Adam MJ, Ruth TJ, Bénard F, Perrin DM, Overall CM. Novelmatrix metalloproteinase inhibitor [18F]marimastat-aryltrifluoroborate as a probe for in vivo positron emission tomography imaging in cancer. Cancer Res. 2010 Oct1;70(19):7562-9. doi: 10.1158/0008-5472.CAN-10-1584. Epub 2010 Aug 20. PubMed PMID: 20729277.

7: van Wijngaarden J, Snoeks TJ, van Beek E, Bloys H, Kaijzel EL, van Hinsbergh VW, Löwik CW. An in vitro model that can distinguish between effects on angiogenesis and on established vasculature: actions of TNP-470, marimastat and the tubulin-binding agent Ang-510. Biochem Biophys Res Commun. 2010 Jan 8;391(2):1161-5. doi: 10.1016/j.bbrc.2009.11.097. Epub 2009 Dec 14. PubMed PMID:20004648.

8: Skipper JB, McNally LR, Rosenthal EL, Wang W, Buchsbaum DJ. In vivo efficacy of marimastat and chemoradiation in head and neck cancer xenografts. ORL J Otorhinolaryngol Relat Spec. 2009;71(1):1-5. doi: 10.1159/000163217. Epub 2008 Oct 16. PubMed PMID: 18931526; PubMed Central PMCID: PMC2700630.

9: Nénan S, Lagente V, Planquois JM, Hitier S, Berna P, Bertrand CP, Boichot E. Metalloelastase (MMP-12) induced inflammatory response in mice airways: effects of dexamethasone, rolipram and marimastat. Eur J Pharmacol. 2007 Mar 15;559(1):75-81. Epub 2006 Dec 12. PubMed PMID: 17234180.

10: Failes TW, Hambley TW. Towards bioreductively activated prodrugs: Fe(III) complexes of hydroxamic acids and the MMP inhibitor marimastat. J Inorg Biochem.2007 Mar;101(3):396-403. Epub 2006 Nov 15. PubMed PMID: 17197030.

11: Failes TW, Cullinane C, Diakos CI, Yamamoto N, Lyons JG, Hambley TW. Studiesof a cobalt(III) complex of the MMP inhibitor marimastat: a potential hypoxia-activated prodrug. Chemistry. 2007;13(10):2974-82. PubMed PMID: 17171733.

12: Groves MD, Puduvalli VK, Conrad CA, Gilbert MR, Yung WK, Jaeckle K, Liu V, Hess KR, Aldape KD, Levin VA. Phase II trial of temozolomide plus marimastat forrecurrent anaplastic gliomas: a relationship among efficacy, joint toxicity and anticonvulsant status. J Neurooncol. 2006 Oct;80(1):83-90. Epub 2006 Apr 25. PubMed PMID: 16639492.

13: Levin VA, Phuphanich S, Yung WK, Forsyth PA, Maestro RD, Perry JR, Fuller GN, Baillet M. Randomized, double-blind, placebo-controlled trial of marimastat in glioblastoma multiforme patients following surgery and irradiation. J Neurooncol. 2006 Jul;78(3):295-302. Epub 2006 Apr 25. PubMed PMID: 16636750.

14: Zucker S, Wang M, Sparano JA, Gradishar WJ, Ingle JN, Davidson NE; Eastern Cooperative Oncology Group. Plasma matrix metalloproteinases 7 and 9 in patientswith metastatic breast cancer treated with marimastat or placebo: Eastern Cooperative Oncology Group trial E2196. Clin Breast Cancer. 2006 Feb;6(6):525-9.PubMed PMID: 16595036.

15: Rosenbaum E, Zahurak M, Sinibaldi V, Carducci MA, Pili R, Laufer M, DeWeese TL, Eisenberger MA. Marimastat in the treatment of patients with biochemically relapsed prostate cancer: a prospective randomized, double-blind, phase I/II trial. Clin Cancer Res. 2005 Jun 15;11(12):4437-43. PubMed PMID: 15958628.

16: Bruce C, Thomas PS. The effect of marimastat, a metalloprotease inhibitor, on allergen-induced asthmatic hyper-reactivity. Toxicol Appl Pharmacol. 2005 Jun 1;205(2):126-32. PubMed PMID: 15893540.

17: Goffin JR, Anderson IC, Supko JG, Eder JP Jr, Shapiro GI, Lynch TJ, Shipp M,Johnson BE, Skarin AT. Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2005 May 1;11(9):3417-24. PubMed PMID: 15867243.

18: Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE. Randomized phase III trial of marimastat versus placebo in patientswith metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. PubMed PMID: 15570070.

19: Jones PH, Christodoulos K, Dobbs N, Thavasu P, Balkwill F, Blann AD, Caine GJ, Kumar S, Kakkar AJ, Gompertz N, Talbot DC, Ganesan TS, Harris AL. Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients withadvanced cancer. Br J Cancer. 2004 Jul 5;91(1):30-6. PubMed PMID: 15162145; PubMed Central PMCID: PMC2364746.

20: Jenssen K, Sewald K, Sewald N. Synthesis of marimastat and a marimastat conjugate for affinity chromatography and surface plasmon resonance studies. Bioconjug Chem. 2004 May-Jun;15(3):594-600. PubMed PMID: 15149188.

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。