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Marimastat(BB-2516)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Marimastat(BB-2516)图片
CAS NO:154039-60-8
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
Marimastat (formerly aslo known as BB2516; BB-2516; TA2516; TA-2516) is an orally bioactive and broad spectrum matrix metalloprotease (MMP) inhibitor with potential anticancer activity. It inhibits MMP-9/2/14/7 with IC50s of 3 nM, 5 nM, 6 nM, 9 nM and 13 nM, respectively. Marimastat was studied in clinical trials but was terminated due to poor performance.
理化性质和储存条件
Molecular Weight (MW)331.41
FormulaC15H29N3O5
CAS No.154039-60-8
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 54 mg/mL (162.9 mM)
Water: <1 mg/mL
Ethanol: 7 mg/mL (21.1 mM)
Solubility (In vivo)50% DMSO+PBS: 30 mg/mL
SynonymsBB 2516; TA-2516; Marimastat; BB-2516; BB2516; TA2516; TA 2516

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

实验参考方法
In Vitro

In vitro activity: Marimastat (100 nM) significantly inhibits the expression of MMP14 in U251, U87, GBM39, and GBM43 tumor cells. Marimastat specifically inhibits the growth of glioma cells and has no effect on normal human astrocytes (NHA). Marimastat early down-regulates the expression of Notch target genes, such as Hes1 and Hes5.


Kinase Assay: Recombinant human MMP2 is activated with 1 mM of 4-aminophenylmercuric acetate for 1 hour at 37°C. Rates of cleavage of 1 μM of the quenched fluorescent MMP substrate (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitrophenyl)-L-2,3-diaminoproprionyl]-Ala-Arg-NH2 are measured in 96-well fluorimetry plates at 37°C 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2, 0.05% Brij 35 using a 320 nm excitation filter and a 405 nm emission filter in the presence of increasing inhibitor concentrations. Curve-fitting and IC50 calculations are done using GraphPad Prism 5.0 Software.


Cell Assay: In co-cultures of tumor spheroids derived from human glioma cell lines U251 and GaMG with RBA, marimastat strongly inhibits tumor invasion at concentrations of 10 μM. Marimastat (10 μM) significantly reduces cell proliferation by 54% and completely inhibits cell growth at 50 μM over 6 days. Also, marimastat (10 μM) reduces U251 spheroid growth by 65%.

In VivoIn an orthotopic oral squamous cell carcinoma implantation model, marimastat (150 mg/kg/day, p.o.) administered by an osmotic pump significantly suppresses the cervical lymph node metastasis and activation of MMP-2, and has a significantly better survival than control group. Marimastat reduces MMP hyperactivity of polycystic human and rat cholangiocytes and blocks the cystic expansion of PCK cholangiocytes. Chronic treatment of 8-week-old PCK rats with marimastat inhibits hepatic cystogenesis and fibrosis.
Animal modelOrthotopic oral squamous cell carcinoma implantation model
Formulation & DosageDissolved in 50% DMSO (v/v) in PBS.; 150 mg/kg; oral gavage
References

Clin Exp Metastasis. 2002;19(6):513-8; Gut. 2014 Oct;63(10):1658-67.

生物活性

Upregulation of MMP14 prolongs survival of glioma patients. Cancer Med. 2013 Aug;2(4):457-67.

Marimastat downregulates MMP14 expression and induces G2/M cell cycle arrest in gliomas. Cancer Med. 2013 Aug;2(4):457-67.

Genetic silencing of MMP14 results in glioma G2/M arrest. Cancer Med. 2013 Aug;2(4):457-67.

Temozolomide and radiation regulate MMP14 expression via microRNA374B in vitro and in vivo. Cancer Med. 2013 Aug;2(4):457-67.

Temozolomide (TMZ) and ionizing radiation (XRT) cooperate with inhibition of MMP14. Cancer Med. 2013 Aug;2(4):457-67.

MMP14 knockdown enhances antiglioma effect mediated by temozolomide (TMZ) and ionizing XRT in U251 glioma model. Cancer Med. 2013 Aug;2(4):457-67.