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.