Other
CN
EU
USA
Description: 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.
References: Pharmacol Ther. 1997;75(1):69-75; Cancer Med. 2013 Aug;2(4):457-67.
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[[email protected]@H](C(C)(C)C)C(NC)=O)[[email protected]](CC(C)C)[[email protected]](O)C(NO)=O
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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%.
Clin Exp Metastasis. 2002;19(6):513-8; Gut. 2014 Oct;63(10):1658-67.
Purity ≥98%
COA
MSDS
NMR