货号:A432881
同义名:
吡啶-4-酰肼
/ INH; Isonicotinic acid hydrazide
Isoniazid 是一种抗菌剂,可抑制脂肪酸合成酶活性,常用于结核病及分枝杆菌感染机制研究。


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| 描述 | Isoniazid (INH) functions as a proagent that requires activation by a specific bacterial enzyme called catalase-peroxidase, named KatG in Mycobacterium tuberculosis, to exert its effects. It is bactericidal against rapidly dividing mycobacteria, exhibiting anti-tuberculostatic activity, but acts as a bacteriostatic agent against slow-growing mycobacteria[1].[2].[3].[4]. |
| 体外研究 | Isoniazid (INH) is a prodrug and must be activated by a bacterial catalase-peroxidase enzyme that in M. tuberculosis is called KatG[1]. Isoniazid is bactericidal to rapidly dividing mycobacteria but is bacteriostatic if the mycobacteria are slow-growing[4]. |
| 作用机制 | Isonicotinic acid hydrazide (INH) passively enters mycobacterial cell through the cell wall and is activated by a mycobacterial enzyme called KatG. Activated IHN led to the accumulation of reactive oxygen species. The produced isonicotinoyl radical binds to a NAD molecule, resulting in the inhibition of FASII enoyl-ACP reductase InhA, which is essential in the mycolic acid biosynthesis pathway. The inhibition impedes cell wall synthesis, and eventually leads to cell death. |
| Concentration | Treated Time | Description | References | |
| Mtb H37Rv | 0.5 μM | To assess the bactericidal activity of NITD-916 against Mtb H37Rv. Results showed rapid killing at concentrations greater than 0.2 μM. | Sci Transl Med. 2015 Jan 7;7(269):269ra3. | |
| Human macrophages | 1 μg/ml | 24 hours | To assess the bactericidal effect of isoniazid on Mtb in human macrophages. Results showed that at a dose of 1 μg/ml, only 2-4% of Mtb survived. | Nat Commun. 2020 Jun 16;11(1):3062. |
| Mtb starved in PBS | 0.5 µg/ml | 7 days | Evaluate the bactericidal effect of isoniazid under nutrient starvation conditions; the ΔcinA mutant was significantly killed by isoniazid in PBS starvation, while wild-type Mtb was unaffected. | Nat Commun. 2022 Apr 22;13(1):2203. |
| Primary mouse bone marrow-derived macrophages (BMDM) | 0.1 µg/ml | 96 hours | Evaluate the bactericidal effect of isoniazid in macrophages; the ΔcinA mutant was significantly killed by isoniazid in IFNγ-activated macrophages, while wild-type Mtb was unaffected. | Nat Commun. 2022 Apr 22;13(1):2203. |
| HCT-116 cells | 10 mM | 24 hours | Induced significant increase in histone and non-histone Kinic levels | Nat Commun. 2021 Sep 20;12(1):5548. |
| HEK293A cells | 10 mM | 24 hours | Induced significant increase in histone and non-histone Kinic levels | Nat Commun. 2021 Sep 20;12(1):5548. |
| HepG2 cells | 10 mM | 24 hours | Identification of histone isonicotinylation sites, revealing 26 unique histone Kinic sites | Nat Commun. 2021 Sep 20;12(1):5548. |
| Adipose-derived mesenchymal stem cells (ADSCs) | 0.5, 1, 5 μg/ml | 24 hours | To evaluate the drug tolerance of Mtb in ADSCs to isoniazid. Results showed that even at high doses of 5 μg/ml, approximately 5% of Mtb survived after INH treatment. At doses of 0.5 and 1 μg/ml, about 10-15% of Mtb were not killed. | Nat Commun. 2020 Jun 16;11(1):3062. |
| Administration | Dosage | Frequency | Description | References | ||
| Mice | Humanized PXR mouse model | Oral | 400 mg/L | 4 weeks | To investigate the hepatotoxicity caused by co-treatment of isoniazid and rifampicin, significant liver injury was observed in humanized PXR mice, characterized by increased serum ALT and ALP activities and bile plugs in the liver. | Nat Med. 2013 Apr;19(4):418-20 |
| BALB/c mice | Acute and established Mycobacterium tuberculosis infection models | Oral | 25 mg/kg | Daily dosing for 4 weeks | To evaluate the in vivo efficacy of NITD-916 in acute and established Mycobacterium tuberculosis infection models. Results showed significant bactericidal activity at 100 mg/kg in both models. | Sci Transl Med. 2015 Jan 7;7(269):269ra3. |
| BALB/c mice and athymic nude mice | Mycobacterium tuberculosis H37Rv infection model | Oral gavage | 10 mg/kg | 5 days per week, for 3 to 12 months | To evaluate the bactericidal effect and relapse prevention of Isoniazid-containing regimens in immune-deficient mice. Results showed that rifapentine-containing regimens achieved sterilization in 3-6 months, while rifampin-containing regimens led to Isoniazid resistance in nude mice. | Am J Respir Crit Care Med. 2011 May 1;183(9):1254-61 |
| Mice | C57BL/6 background mice | Oral gavage | 50 mg/kg/day | Once daily for ten days | Increased histone and non-histone Kinic levels in liver tissues of mice after INH treatment | Nat Commun. 2021 Sep 20;12(1):5548. |
| C57BL/6 mice | Tuberculosis infection model | Oral gavage | 10 mg/kg | Once daily for 4 to 8 weeks | To evaluate the therapeutic effect of isoniazid on tuberculosis in vivo. Results showed that INH treatment significantly reduced bacterial load in the lungs and spleen, especially after 8 weeks of treatment. The combination of celecoxib and INH showed a more significant reduction in bacterial load at both 4 and 8 weeks post-treatment. | Nat Commun. 2020 Jun 16;11(1):3062. |
| BALB/c mice | Mouse model of TB | Oral gavage | 0.5, 1.5 and 6.0 mg/kg/day | 5 days per week for 42 days | To evaluate the virulence and INH resistance of the ΔsigI mutant in a mouse model, results showed that the ΔsigI mutant was more virulent than wild-type and had higher survival in the presence of INH | Nat Commun. 2012 Mar 20;3:753 |
| Mice | Tuberculosis model | Oral | 70 mg/kg | Five days a week for four weeks | To evaluate the therapeutic effect of isoniazid combined with rifampicin in tuberculosis-infected mice, results showed that nebulized cellulase enhanced the antimycobacterial activity of isoniazid and rifampicin | Nat Commun. 2021 Mar 11;12(1):1606 |
| BALB/c mice | Mouse model of tuberculosis | Oral | 25 and 50 mg/kg (daily and thrice-weekly administration) | Administered daily (5/7) or thrice-weekly (3/7) for 8, 10, or 12 weeks | To evaluate the bactericidal activity and treatment-shortening potential of isoniazid in rifapentine-based regimens. Results showed that daily or thrice-weekly PHZ regimens achieved stable cure within 10-12 weeks. | Am J Respir Crit Care Med. 2008 Nov 1;178(9):989-93 |
| C57BL/6 mice | Chronic tuberculosis infection model | Drinking water | 10 mg/kg/day, 5 mg/kg/day, 2.5 mg/kg/day | 12 weeks | Evaluate the bactericidal effect of isoniazid in chronically infected mice; the ΔcinA mutant was significantly killed by isoniazid during the chronic phase, while the killing effect on wild-type Mtb was poor. | Nat Commun. 2022 Apr 22;13(1):2203. |
| Dose | Rat: 0.05 g/kg[3] (s.c.) |
| Administration | s.c. |
| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 |
| NCT02114684 | Recurrent Tuberculosis | Phase 1 Phase 2 | Completed | - | South Africa ... 展开 >> CAPRISA eThekwini Clinical Research Site (eCRS) Durban, KwaZulu Natal, South Africa, 4001 收起 << |
| NCT00018083 | Tuberculosis ... 展开 >>HIV Infections 收起 << | Not Applicable | Unknown | - | United States, North Carolina ... 展开 >> Duke University Medical Center Recruiting Durham, North Carolina, United States, 27710 Contact: Carol D Hamilton, M.D. 919-684-3279 收起 << |
| NCT02381470 | Tuberculosis | Phase 2 | Not yet recruiting | March 2018 | Philippines ... 展开 >> Lung Center Philippines Not yet recruiting Manila, Philippines Contact: Vincent Balanag Principal Investigator: Vincent Balanag Philippines Tuberculosis Society (Quezon Institute) Not yet recruiting Manila, Philippines Contact: Jubert Benedicto Principal Investigator: Jubert Benedicto Singapore Changi General Hospital Not yet recruiting Singapore, Singapore Contact: Augustine Tee Principal Investigator: Augustine Tee National University Hospital, Singapore Not yet recruiting Singapore, Singapore Contact: Meera Gurumurthy +65 6772 7861 meera@nuhs.edu.sg Principal Investigator: Nicholas Paton 收起 << |
| 计算器 | ||||
| 存储液制备 | ![]() |
1mg | 5mg | 10mg |
|
1 mM 5 mM 10 mM |
7.29mL 1.46mL 0.73mL |
36.46mL 7.29mL 3.65mL |
72.92mL 14.58mL 7.29mL |
|
| CAS号 | 54-85-3 |
| 分子式 | C6H7N3O |
| 分子量 | 137.14 |
| SMILES Code | NNC(=O)C1=CC=NC=C1 |
| MDL No. | MFCD00006426 |
| 别名 | 吡啶-4-酰肼 ;INH; Isonicotinic acid hydrazide; Isoniazid, Isonicotinylhydrazide, Hydra, Hyzyd, Isovit, Nydrazid; NSC 9659; Isonicotinylhydrazide; Isonicotinic hydrazide |
| 运输 | 蓝冰 |
| InChI Key | QRXWMOHMRWLFEY-UHFFFAOYSA-N |
| Pubchem ID | 3767 |
| 存储条件 |
In solvent -20°C: 3-6个月 -80°C: 12个月 Pure form Keep in dark place, inert atmosphere, room temperature |
| 溶解方案 |
DMSO: 50 mg/mL(364.59 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO H2O: 30 mg/mL(218.75 mM),配合低频超声助溶 以下溶解方案都请先按照体外实验的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
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