154039-60-8
154039-60-8 structure
- Name: Marimastat (BB-2516)
- Chemical Name: (2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N',3-dihydroxy-2-(2-methylpropyl)butanediamide
- CAS Number: 154039-60-8
- Molecular Formula: C15H29N3O5
- Molecular Weight: 331.408
- Catalog: Biochemical Inhibitor Proteases MMP inhibitor
- Create Date: 2018-07-19 21:49:45
- Modify Date: 2024-01-03 20:31:42
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Marimastat is a broad spectrum inhibitor of MMPs with IC50 values of 3, 5, 6, 9 and 13 nM for MMP-9, MMP-1, MMP-2, MMP-14 and MMP-7, respectively.
| Name | (2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N',3-dihydroxy-2-(2-methylpropyl)butanediamide |
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| Synonyms |
Marimastat
(2S,3R)-N-[(2S)-3,3-Dimethyl-1-(methylamino)-1-oxo-2-butanyl]-N,2-dihydroxy-3-isobutylsuccinamide BB-2516 Butanediamide, N-[(1S)-2,2-dimethyl-1-[(methylamino)carbonyl]propyl]-N,2-dihydroxy-3-(2-methylpropyl)-, (2S,3R)- (2S,3R)-N-[(2S)-3,3-Dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N,2-dihydroxy-3-isobutylsuccinamide (2S,3R)-N4-((1S)-2,2-Dimethyl-1-((methylamino)carbonyl)propyl)-N1,2-dihydroxy-3-(2-methylpropyl)butanediamide (2S,3R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N,2-dihydroxy-3-(2-methylpropyl)butanediamide |
| Description | Marimastat is a broad spectrum inhibitor of MMPs with IC50 values of 3, 5, 6, 9 and 13 nM for MMP-9, MMP-1, MMP-2, MMP-14 and MMP-7, respectively. |
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| Related Catalog | |
| Target |
IC50: 3 nM (MMP-9), 5 nM (MMP-1), 6 nM (MMP-2), 9 nM (MMP-14), 13 nM (MMP-7) |
| In Vitro | Cyclam-marimastat conjugate and its metal complexes exhibit slightly reduced potency against MMP-1, but essentially identical inhibitory activity against MMP-3[1]. Marimastat (1 μM) shows inhibition of vascular outgrowth, and selectively affects angiogenesis[2]. |
| In Vivo | Animals receiving chemoradiation + marimastat (8.7 mg/kg) have statistically significant delayed growth, compared to animals receiving chemoradiation alone. Marimastat may work in combination with chemotherapy and radiation to inhibit tumor growth[3]. |
| Kinase Assay | Compounds 1, 2, 7-9 and 11-16 are pre-incubated with MMP-1 or MMP-3 (10 nM) at different concentrations (0-10 μM) in a mixture of Tris-HCl (50 mM, pH 7.5), NaCl (150 mM), CaCl2 (10 mM), NaN3 (0.02%) and Brij-35 (0.05%) for 1 hour at 37°C. Residual activity is measured using the fluorogenic MMP substrate (2 μM) by fluorescence increase (emission at 393 nm and excitation at 325 nm) on a fluorescence plate reader. The data are fitted to the tight binding inhibitor equation: v=[(E-I-k+[(E-I-k)2+4Ek]1/2)/(2E)], where v is the velocity of the reaction, E is the enzyme concentration, I is the initial inhibitor concentration, and k is the apparent inhibition constant, using the software Prism. |
| Animal Admin | Three-month-old female nude mice are inoculated using a trochar needle with 2 mm2 established SCC-1 tissue subcutaneously in the flank. Treatment started once the tumors are 5-6 mm in diameter. Mice are randomLy divided into groups of 8 mice to receive different treatments: (1) control, (2) marimastat alone, (3) cisplatin + radiation in combination and (4) marimastat + cisplatin + radiation in combination. All animalsreceive a 14-day osmotic pump containing dimethylsulfoxide (DMSO) as a control for both the pump and vehicle. Animals treated with marimastatreceive the same osmotic pump containing 200 μL of marimastat with DMSO to result in a daily dose of 8.7 mg/kg 10 days after the initiation of treatment. Lead-shielded animalsreceive 8 Gy of 60Co radiation to the exposed tumor, divided into 4 fractions on days 8, 12, 16 and 20. A dose of 8 Gy is chosen because 7.5 Gy (7,500 rad) has been shown in previous experiments to inhibit tumor growth without being a curative dose. Animals receive 4 intraperitoneal doses of cisplatin (3 mg/kg) 1 h before each fraction of radiation. Tumors are measured biweekly for 32 days. Potential treatment toxicity is monitored using mouse weight. Tumor size (surface area equal to product of two largest diameters) and regression rates are determined in each treatment group. After 32 days, tumors are harvested for immunohistochemistry. Day 32 is chosen due to death of control group animals and euthanization of animals showing clinical signs of illness to allow for statistical analysis of data acquired from surviving animals. |
| References |
| Density | 1.1±0.1 g/cm3 |
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| Melting Point | 148℃ |
| Molecular Formula | C15H29N3O5 |
| Molecular Weight | 331.408 |
| Exact Mass | 331.210724 |
| PSA | 127.76000 |
| LogP | -0.16 |
| Index of Refraction | 1.499 |
| Storage condition | -20℃ |
| RIDADR | NONH for all modes of transport |
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| HS Code | 29241990 |