Prinomastat (AG3340)
(Synonyms: 普啉司他; AG3340; KB-R9896) 目录号 : GC32951
An inhibitor of MMP-2, -3, -9, -13, and -14
Cas No.:192329-42-3
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
Prinomastat is an inhibitor of matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-9, MMP-13, and MMP-14 (IC50s = 0.05, 0.3, 0.26, 0.03, and 0.33 nM, respectively).1 It is selective for these MMPs over MMP-1 and MMP-7 (IC50s = 8.3 and 54 nM, respectively). Prinomastat (50 mg/kg) reduces tumor growth and inhibits the formation of lung metastases in a murine Lewis lung carcinoma model. It also reduces the incidence of kidney, but not brain, metastasis and tumor microvessel density in an NCI H460 lung cancer orthotopic mouse model when administered at a dose of 100 mg/kg.2 Prinomastat reduces bronchoalveolar lavage fluid (BALF) levels of TNF-α and pulmonary edema in a rat model of ventilator-induced lung injury.3
1.Scatena, R.Prinomastat, a hydroxamate-based matrix metalloproteinase inhibitor. A novel pharmacological approach for tissue remodelling-related diseasesExpert Opin. Investig. Drugs9(9)2159-2165(2000) 2.Liu, J., Tsao, M.S., Pagura, M., et al.Early combined treatment with carboplatin and the MMP inhibitor, prinomastat, prolongs survival and reduces systemic metastasis in an aggressive orthotopic lung cancer modelLung Cancer42(3)335-344(2003) 3.Foda, H.D., Rollo, E.E., Drews, M., et al.Ventilator-induced lung injury upregulates and activates gelatinases and EMMPRIN: Attenuation by the synthetic matrix metalloproteinase inhibitor, Prinomastat (AG3340)Am. J. Respir. Cell Mol. Biol.25(6)717-724(2001)
| Cas No. | 192329-42-3 | SDF | |
| 别名 | 普啉司他; AG3340; KB-R9896 | ||
| Canonical SMILES | O=C([C@@H]1N(S(=O)(C2=CC=C(OC3=CC=NC=C3)C=C2)=O)CCSC1(C)C)NO | ||
| 分子式 | C18H21N3O5S2 | 分子量 | 423.51 |
| 溶解度 | Soluble in DMSO | 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 | 2.3612 mL | 11.8061 mL | 23.6122 mL |
| 5 mM | 0.4722 mL | 2.3612 mL | 4.7224 mL |
| 10 mM | 0.2361 mL | 1.1806 mL | 2.3612 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。
Prinomastat, a hydroxamate-based matrix metalloproteinase inhibitor. A novel pharmacological approach for tissue remodelling-related diseases
Expert Opin Investig Drugs 2000 Sep;9(9):2159-65.PMID:11060800DOI:10.1517/13543784.9.9.2159.
Prinomastat (formerly AG3340, Agouron Pharmaceuticals, Inc.) is a potent, selective oral inhibitor of matrix metalloproteinase-2, -9, -13 and -14. This peculiar selectivity should represent an advantage for Prinomastat in terms of efficacy/tolerability. The drug has been shown to inhibit tumour growth and angiogenesis in a variety of preclinical models, including cancer of colon, breast, lung and intriguingly in melanoma and glioma models. Moreover, the combination of Prinomastat and several chemotherapeutic agents was shown to induce additive effects. The drug is currently in Phase III clinical trials for patients with non-small cell lung cancer in combination with paclitaxel and carboplatin, as well as in advanced hormone refractory prostate cancer in combination with mitoxantrone. The most common side effects are musculoskeletal pain and stiffness. These side effects generally cease with treatment interruption. Finally, considering the pathophysiology of MMPs, Agouron is exploring the utility of Prinomastat in ophthalmology and dermatology.
The effect of Prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinases, on uveal melanoma rabbit model
Curr Eye Res 2002 Feb;24(2):86-91.PMID:12187478DOI:10.1076/ceyr.24.2.86.8159.
Purpose: We studied the effects of intravitreally administered prinomastat on the take rate and growth of uveal melanoma after xenograft implantation in rabbit uveal melanoma model. Methods: Uveal melanoma xenograft was implanted to suprachoroidal space in each eye of 24 pigmented rabbits which were immunosuppressed with cyclosporine. One week after surgery, the eyes were randomized to receive prinomastat or the vehicle of the prinomastat intravitreally every week for 4 weeks. The take rate of the xenograft, tumor height, apoptosis, and necrosis in the eyes which developed tumors from the treatment and control groups were compared. Results: A tumor mass was identified in 8 of 24 (33%) prinomastat-treated eyes and 20 of 24 (83%) of the vehicle-treated eyes. Echographic measurements revealed a mean tumor height of 2.2 mm in the prinomastat-treated group and 3.8 mm in the control group in those eyes with take of tumor (p < 0.001). Stereomicroscopic measurements showed a mean tumor height of 1.9 mm in the treatment group and 3.9 mm in the control group (p < 0.001). The mean number of apoptotic nuclei detected per mm(2) of the histologic section in the non-necrotic tumor was 8.12 in the prinomastat-treated group and 0.57 in the control group (p < 0.001). Evaluation of the digital images in microscopic sections of the tumors on histologic slides revealed 29.6% necrosis in prinomastat-treated eyes as compared to 10.9% in vehicle-treated eyes (p = 0.003). Conclusions: These results suggest that prinomastat treatment significantly reduces the take rate and the growth rate of xenograft in uveal melanoma rabbit model.
The effect of Prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinases, on posttraumatic proliferative vitreoretinopathy
Ophthalmic Res 2001 Jan-Feb;33(1):20-3.PMID:11114600DOI:10.1159/000055636.
In a search for a pharmacologic adjuvant in the management of posttraumatic proliferative vitreoretinopathy (PVR), we investigated the effect of intravitreal injection of Prinomastat (AG3340) on an experimental model. Posterior penetrating eye trauma was created in one eye each of 24 New Zealand white rabbits. One week after the surgery, all rabbits were randomized (1:1) to receive 0.5 mg prinomastat or the vehicle of the drug intravitreally every week for 6 weeks. The degree of PVR for each hemiretina was scored, and the two scores were summed to obtain a total eye score. The mean total eye score was 3.58 in the treatment group and 5.75 in the control group (p = 0.0307). The numbers of eyes with tractional retinal detachment in the prinomastat-treated (n = 12) and control (n = 12) groups were 3 and 9, respectively (p = 0.0391). These results suggest that intravitreally administered prinomastat has an inhibitory effect on posttraumatic PVR.
Evaluation of intraocular pharmacokinetics and toxicity of Prinomastat (AG3340) in the rabbit
J Ocul Pharmacol Ther 2001 Jun;17(3):295-304.PMID:11436949DOI:10.1089/108076801750295326.
To determine the ocular pharmacokinetics, physiological and histological effects of prinomastat (a matrix metalloprotease inhibitor), a total of seventy-seven eyes of New Zealand White rabbits received intravitreous and subtenon injections of prinomastat or of acidified water vehicle as control, Doses of 0.5 mg in 0.05 mL of prinomastat or acidified water were used for intravitreal injection. For the subtenon injections, doses of 5 mg prinomastat in 0.5 mL of acidified water were administered in the superotemporal quadrant. Intraocular pharmacokinetics were determined by analyzing vitreous samples at different postinjection time points using Liquid Chromatography-Mass Spectroscopy/Mass Spectroscopy (LC-MS/MS). The toxicity was evaluated by biomicroscopy, electroretinography (ERG), pneumatonometry, and histology. No toxicity was found with either administration method. At day 14 after intravitreal injection, levels of prinomastat in the vitreous and choroid were 1.4 ng/mg and 7.8 ng/mg, respectively. The retinal levels of prinomastat were 22 ng/mg at 24 hr and dropped below 1 ng/mg at 48 hr. Prinomastat remained well above minimum effective concentration in the choroid for at least four weeks after a single intravitreal injection, suggesting that local intravitreal injection may have potential in treating choroidal neovascularization.
The effect of Prinomastat (AG3340), a potent inhibitor of matrix metalloproteinases, on a subacute model of proliferative vitreoretinopathy
Curr Eye Res 2000 Jun;20(6):447-53.PMID:10980656doi
Purpose: To determine the efficacy of Prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinase, in the treatment of experimental proliferative vitreoretinopathy (PVR) induced by intravitreal dispase injection. Methods: One eye each of 53 New Zealand white rabbits was injected in the vitreous cavity with 0.07 unit of dispase to induce PVR. One week after PVR induction, 53 rabbits were randomized (27:26) to receive 0.5 mg prinomastat or the vehicle of the drug (acidified water) intravitreally every two weeks. The scores of PVR severity (scale of 1-5) were graded to compare the prinomastat-treated animals with the control group. Results: The average PVR scores in the treatment and control groups were 2.62 and 3.57 respectively (p = 0.038; Wilcoxon rank sum). Clinically significant PVR with retinal detachment (PVR > or = grade 3) developed in 76% of rabbits in the control group versus 51% of rabbits treated with prinomastat. Conclusions: Intravitreally administered prinomastat decreased development of PVR in an experimental model which made use of dispase to induce PVR.