Marimastat (BB2516) is a broad spectrum and orally bioavailable inhibitor of MMPs, with potent activity against MMP-9 (IC₅₀=3 nM), MMP-1 (IC₅₀=5 nM), MMP-2 (IC₅₀=6 nM), MMP-14 (IC₅₀=9 nM) and MMP-7 (IC₅₀=13 nM), used in the treatment of cancer. Marimastat (BB2516) is an angiogenesis and metastasis inhibitor, which limits the growth and production of blood vessels. As an antimetatstatic agent it prevents malignant cells from breaching the basement membranes^[1][2].

Marimastat (BB2516) (1 μM) shows inhibition of vascular outgrowth, and selectively affects angiogenesis^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animals receiving chemoradiation + Marimastat (BB2516) (8.7 mg/kg) have statistically significant delayed growth, compared to animals receiving chemoradiation alone. Marimastat (BB2516) may work in combination with chemotherapy and radiation to inhibit tumor growth^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

331.41

C₁₅H₂₉N₃O₅

154039-60-8

马立马司他

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL (301.74 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (7.54 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.54 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (7.54 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.54 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (7.54 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.54 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Rasmussen HS, et al. Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther. 1997;75(1):69-75.

  [2]. Yu M, et al. Incorporation of Bulky and Cationic Cyclam-Triazole Moieties into Marimastat Can Generate Potent MMP Inhibitory Activity without Inducing Cytotoxicity. ChemistryOpen. 2013 Jun;2(3):99-105.

  [3]. van Wijngaarden J, et al. 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.

  [4]. Skipper JB, et al. In vivo efficacy of marimastat and chemoradiation in head and neck cancer xenografts. ORL J Otorhinolaryngol Relat Spec. 2009;71(1):1-5.

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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Rasmussen HS, et al. Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther. 1997;75(1):69-75.

  [2]. Yu M, et al. Incorporation of Bulky and Cationic Cyclam-Triazole Moieties into Marimastat Can Generate Potent MMP Inhibitory Activity without Inducing Cytotoxicity. ChemistryOpen. 2013 Jun;2(3):99-105.

  [3]. van Wijngaarden J, et al. 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.

  [4]. Skipper JB, et al. In vivo efficacy of marimastat and chemoradiation in head and neck cancer xenografts. ORL J Otorhinolaryngol Relat Spec. 2009;71(1):1-5.