PA-824
(Synonyms: (S)-6,7-二氢-2-硝基-6-[[4-(三氟甲氧基)苯基]甲氧基]-5H-咪唑并[2,1-B][1,3]恶嗪,Pretomanid) 目录号 : GC13561
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PA-824是一种硝基咪唑类抗结核药物，PA-824可通过抑制结核分枝杆菌细胞壁合成和干扰能量代谢来杀灭细菌。
Cas No.:187235-37-6
Sample solution is provided at 25 µL, 10mM.
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PA-824 is a nitroimidazole anti-tuberculosis drug. PA-824 kills bacteria by inhibiting Mycobacterium tuberculosis cell wall synthesis and interfering with energy metabolism[1-2]. PA-824 can be used in research related to multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis[3-4].
In vitro, PA-824 (2.5-10µg/ml) was used to treat M. leprae and M. tuberculosis for 7 days. PA-824 had no effect on the viability of M. leprae, PA-824 significantly reduced the proliferation of M. tuberculosis[5]. PA-824 (0.015-16µg/ml) was used to treat M. avium, M. intracellulare, M. abscessus, and M. massiliense for 3-14 days. The inhibitory effect of PA-824 on these five mycobacterial species was generally weak, with minimum inhibitory concentration (MIC) values all greater than 16µg/ml[6].
In vivo, PA-824 (200mg/kg/day) was administered by oral gavage to BALB/c mice infected with M. avium, M. abscessus, M. chelonae, or M. fortuitum (once daily, starting 7 days after infection, for 28 days). PA-824 demonstrated strong antibacterial activity in the lungs and spleens of mice infected with M. abscessus, and weak activity in the kidneys of mice infected with M. fortuitum. PA-824 showed no significant antibacterial effect in the mouse models infected with M. avium or M. chelonae[7]. PA-824 (40-80mg/kg/day) was administered by oral gavage to Tg.rasH2 mice (once daily for 26 weeks). The mice, exposed to PA-824 at levels exceeding the clinical human exposure dose, did not exhibit drug-related early death, tumors, or non-tumorigenic microscopic pathological changes[8].
References:
[1] Keam SJ. Pretomanid: First Approval. Drugs. 2019 Nov;79(16):1797-1803. doi: 10.1007/s40265-019-01207-9.
[2] Gils T, Lynen L, de Jong BC, et al. Pretomanid for tuberculosis: a systematic review. Clin Microbiol Infect. 2022 Jan;28(1):31-42.
[3] Deb U, Biswas S. Pretomanid: The latest USFDA-approved anti-tuberculosis drug. Indian J Tuberc. 2021 Apr;68(2):287-291.
[4] Koehler N, Andres S, Merker M, et al. Pretomanid-resistant tuberculosis. J Infect. 2023 May;86(5):520-524.
[5] Manjunatha UH, Lahiri R, Randhawa B, et al. Mycobacterium leprae is naturally resistant to PA-824. Antimicrob Agents Chemother. 2006 Oct;50(10):3350-4.
[6] Zheng H, Wang Y, He W, et al. In Vitro Activity of Pretomanid against Nontuberculous Mycobacteria. Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0181021.
[7] Zheng L, Qi X, Zhang W, et al. Efficacy of PBTZ169 and pretomanid against Mycobacterium avium, Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum in BALB/c mice models. Front Cell Infect Microbiol. 2023 Mar 22;13:1115530.
[8] Ambroso JL, Dillberger J, Bruning-Barry R, et al. Assessment of the Carcinogenic Potential of Pretomanid in Transgenic Tg.rasH2 Mice. Int J Toxicol. 2022 Sep-Oct;41(5):367-379.
PA-824是一种硝基咪唑类抗结核药物，PA-824可通过抑制结核分枝杆菌细胞壁合成和干扰能量代谢来杀灭细菌[1-2]。PA-824可用于多重耐药结核病和广泛耐药结核病的相关研究[3-4]。
在体外，PA-824（2.5-10μg/ml）在处理麻风分枝杆菌和结核分枝杆菌7天，PA-824对麻风分枝杆菌的活力没有影响，PA-824可显著降低结核分枝杆菌的增殖[5]。PA-824（0.015-16μg/ml）处理鸟分枝杆菌、胞内分枝杆菌、脓肿分枝杆菌和马赛分枝杆菌3-14天，PA-824对这五种分枝杆菌的抑制效果一般，最小抑菌浓度（MIC）都大于16μg/ml[6]。
在体内，PA-824（200mg/kg/day）灌胃处理感染鸟分枝杆菌、脓肿分枝杆菌、龟分枝杆菌或偶发分枝杆菌的BALB/c小鼠（每日一次，从感染后第7天开始，持续28天），PA-824在脓肿分枝杆菌感染小鼠的肺部和脾脏显示出较强的抗菌活性，在偶发分枝杆菌感染小鼠的肾脏显示出较弱的抗菌活性，但在鸟分枝杆菌和龟分枝杆菌感染模型中未显示出显著的抗菌效果[7]。PA-824（40-80mg/kg/day）灌胃处理Tg.rasH2小鼠（每日一次，持续26周），小鼠在高于人用临床暴露剂量的PA-824暴露水平下，未出现药物相关的早期死亡、肿瘤或非肿瘤性微观病理改变的现象[8]。
| Cell experiment [1]: | |
Cell lines | Mycobacterium tuberculosis, Mycobacterium leprae |
Preparation Method | Resident peritoneal macrophages from Swiss mice were harvested and adhered. For M. leprae, macrophages were infected overnight with fresh, mouse-derived M. leprae at a multiplicity of infection (MOI) of 20:1 at 33°C. For M. tuberculosis, macrophages were infected with M. tuberculosis at an MOI of 2:1 for 30 min at 37°C. Infected macrophages were incubated with PA-824 (2.5-10μg/ml) in culture medium for 7 days. PA-824 was also tested in axenic BACTEC 7H12B medium with M. leprae. |
Reaction Conditions | 2.5-10μg/ml; 7 day. |
Applications | PA-824 had no effect on the metabolic activity of M. leprae in either axenic culture or within infected macrophages. In contrast, in M. tuberculosis-infected macrophages, PA-824 treatment resulted in at least a 2-log (100-fold) reduction in colony-forming units. |
| Animal experiment [2]: | |
Animal models | BALB/c mice |
Preparation Method | Mice were inoculated intravenously in the tail vein with M. avium, M. abscessus, M. chelonae, or M. fortuitum. Dexamethasone (5mg/kg; daily) was administered 1 week prior to infection and stopped 6 days after infection. Mice were treated with drugs for 28 days starting 7 days after infection. PA-824 (200mg/kg/day) was administered by gavage. |
Dosage form | 200mg/kg/day; Oral gavage; 28 days. |
Applications | In M. abscessus-infected mice, PA-824 treatment significantly reduced the bacterial load in the lungs and spleen compared to the untreated control. In M. fortuitum-infected mice, PA-824 showed only weak activity in the kidneys. PA-824 showed no significant inhibitory effect against M. avium and had little activity against M. chelonae in mice. |
References: | |
| Cas No. | 187235-37-6 | SDF | |
| 别名 | (S)-6,7-二氢-2-硝基-6-[[4-(三氟甲氧基)苯基]甲氧基]-5H-咪唑并[2,1-B][1,3]恶嗪,Pretomanid | ||
| 化学名 | (6S)-2-nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine | ||
| Canonical SMILES | C1C(COC2=NC(=CN21)[N+](=O)[O-])OCC3=CC=C(C=C3)OC(F)(F)F | ||
| 分子式 | C14H12F3N3O5 | 分子量 | 359.26 |
| 溶解度 | ≥ 17.85mg/mL 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 | 2.7835 mL | 13.9175 mL | 27.835 mL |
| 5 mM | 556.7 μL | 2.7835 mL | 5.567 mL |
| 10 mM | 278.3 μL | 1.3917 mL | 2.7835 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。
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
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