product name Marimastat(BB-2516)
Description: Marimastat, aslo known as BB-2516 and TA-2516, is an orally active, synthetic, broad spectrum matrix metalloprotease (MMP) inhibitor for MMP-9, MMP-1, MMP-2, MMP-14 and MMP-7 with IC50 of 3 nM, 5 nM, 6 nM, 9 nM and 13 nM, respectively. 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.
References: Pharmacol Ther. 1997;75(1):69-75; Cancer Med. 2013 Aug;2(4):457-67.
331.41
Formula
C15H29N3O5
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
Synonyms
BB-2516 and TA-2516
other peoduct :
| 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 Vivo | In 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 model | Orthotopic oral squamous cell carcinoma implantation model |
| Formulation & Dosage | Dissolved 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. |
