XL-784 free base
目录号 : GC38871
XL-784 free base 是 MMP 的一个选择性抑制剂，其对 MMP-1，MMP-3，MMP-8，MMP-9，MMP-13 的 IC50 值分别约为 1900，0.81，120，10.8，18，0.56 nM。
Cas No.:1356992-21-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Animal Administration: [2]Mice[2]A total of 89 mice undergo aortic perfusion. Beginning the day of perfusion, animals are treated with the study drug (e.g., XL-784), a negative control, or doxycycline. 76 animals survive to sacrifice and are included in the analysis. Animals treated with the experimental agent, XL-784, receive gavage daily with the agent diluted in 0.1 mL of Cremophor, a nonionic castor oil-based solubilizer and emulsifying agent. Three doses of the drug are used, 50 (n=17), 125 (n=17), and 250 mg/kg per d (n=18) administered as a single daily dose. The fifth group of mice do not receive a gavage treatment but are treated with doxycycline (n=19) in their drinking water at a concentration 100 mg/kg per d of the animals. In the second treatment protocol, a total of 50 animals underwent aortic perfusion and 47 animals survive for analysis at 14 days. The 5 treatment groups are XL-784 at 250, 375, or 500 mg/kg, Cremaphor diluent alone, or doxycycline 100 mg/kg. Animals are assigned in groups of 3 to a treatment group rotating randomly through each treatment group until there are 9 animals in each group except for the 500 mg/kg per d group which totaled to 14 animals[2]. |
References: [1]. Williams JM, et al. Evaluation of metalloprotease inhibitors on hypertension and diabetic nephropathy. Am J Physiol Renal Physiol. 2011 Apr;300(4):F983-98. | |
XL-784 free base is a selective matrix metalloproteinases (MMP) inhibitor, with IC50s of ~1900, 0.81, 120, 10.8, 18, 0.56 nM for MMP-1，MMP-2，MMP-3，MMP-8，MMP-9，MMP-13，respectively.
XL-784 is a highly potent, low-molecular-weight (1,122 g/mol) inhibitor of MMPs that has very limited aqueous solubility (20 μg/mL). XL-784 potently inhibits MMP-2, MMP-13, andADAM10 [TNF-α-converting enzyme (TACE)] activity in vitro, with IC50 values in the range of 1-2 nM. XL-784 also inhibits MMP-9 (IC50 ~20 nM) activity and ADAM17 (IC50 ~70 nM) also known as TACE. However, it exhibits low potency for inhibition of MMP-1 (IC50 ~2,000 nM)[1].
All mice tolerate the treatments similarly. Control mice all developed aneurysms with a mean %△AD of 158.5%±4.3%. Treatment with all doses of XL-784 and doxycycline are effective in inhibiting aortic dilatation. There is a clear dose-response relationship between XL-784 and reductions in aortic dilatation at harvest (50 mg/kg 140.4% ±3.2%; 125 mg/kg 129.3% ±5.1%; 250 mg/kg 119.2%±3.5%; all Ps<0.01 compared to control). This continues with the higher doses (375 mg/kg 88.6%±4.4%; 500 mg/kg 76.0%±3.5%). The highest 2 doses of XL-784 tested are more effective than doxycycline (112.2%±2.0%, P<0.05) in inhibiting maximal dilatation of the aorta after elastase perfusion[2].
[1]. Williams JM, et al. Evaluation of metalloprotease inhibitors on hypertension and diabetic nephropathy. Am J Physiol Renal Physiol. 2011 Apr;300(4):F983-98. [2]. Ennis T, et al. Effect of novel limited-spectrum MMP inhibitor XL784 in abdominal aortic aneurysms. J Cardiovasc Pharmacol Ther. 2012 Dec;17(4):417-26.
| Cas No. | 1356992-21-6 | SDF | |
| Canonical SMILES | O=C(N1CC(C(NO)=O)N(S(=O)(C2=CC(F)=C(OC3=CC=C(Cl)C=C3)C(F)=C2)=O)CC1)OCCOC | ||
| 分子式 | C21H22ClF2N3O8S | 分子量 | 549.93 |
| 溶解度 | DMSO: 250 mg/mL (454.60 mM) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8184 mL | 9.0921 mL | 18.1841 mL |
| 5 mM | 0.3637 mL | 1.8184 mL | 3.6368 mL |
| 10 mM | 0.1818 mL | 0.9092 mL | 1.8184 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。