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Isoniazid/异烟肼 {[allProObj[0].p_purity_real_show]}

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。

Isoniazid/异烟肼 化学结构 CAS号:54-85-3
Isoniazid/异烟肼 化学结构
CAS号:54-85-3
Isoniazid/异烟肼 3D分子结构
CAS号:54-85-3
Isoniazid/异烟肼 化学结构 CAS号:54-85-3
Isoniazid/异烟肼 3D分子结构 CAS号:54-85-3
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Isoniazid/异烟肼 生物活性

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.

Isoniazid/异烟肼 细胞实验

Cell Line
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.

Isoniazid/异烟肼 动物实验

Species
Animal Model
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.

Isoniazid/异烟肼 动物研究

Dose Rat: 0.05 g/kg[3] (s.c.)
Administration s.c.

Isoniazid/异烟肼 临床研究

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 <<

Isoniazid/异烟肼 参考文献

[1]Suarez, J., et al., An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG). J Biol Chem, 2009. 284(11): p. 7017-29.

[2]Timmins, G.S., et al., Nitric oxide generated from isoniazid activation by KatG: source of nitric oxide and activity against Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2004. 48(8): p. 3006-9.

[3]Singh, R., et al., PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science, 2008. 322(5906): p. 1392-5.

[4]Ahmad, Z., et al., Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant, Mycobacterium tuberculosis in the guinea pig. J Infect Dis, 2009. 200(7): p. 1136-43.

Isoniazid/异烟肼 实验方案

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

Isoniazid/异烟肼 技术信息

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

请根据您的动物给药指南选择适当的溶解方案。
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
方案 一
方案 二
方案 三
配制的工作液建议现用现配,短期内尽快用完。 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
方案 一
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