Acetylisoniazid (INH-Ac) is a prodrug of isoniazid (INH), a first-line anti-tuberculosis drug. It was synthesized in the 1950s and is produced by acetylation of isoniazid. INH-Ac is more lipophilic than INH, which allows it to better penetrate the mycobacterial cell wall. Once inside the cell, it is hydrolyzed to INH, which inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall. INH-Ac has been investigated for its potential to improve the pharmacokinetic properties of INH, including its bioavailability, half-life, and tissue distribution. It has also been studied for its potential to reduce the side effects of INH, such as hepatotoxicity. However, INH-Ac has shown limited clinical efficacy compared to INH, and it is not currently used as a standard treatment for tuberculosis.'
acetylisoniazid: Antitubercular Agent [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
N'-acetylisoniazid : A carbohydrazide resulting from the formal condensation of the carboxy group of isonicotinic acid with hydrazine and subsequent acetylation of the monosubstituted nitrogen atom. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 71602 |
| CHEMBL ID | 1442231 |
| CHEBI ID | 7207 |
| SCHEMBL ID | 1415953 |
| MeSH ID | M0498795 |
| Synonym |
|---|
| MLS000526155 |
| smr000116629 |
| 4-pyridinecarboxylicacid, 2-acetylhydrazide |
| n'-acetylisoniazid |
| CHEBI:7207 , |
| acetyl isoniazid |
| n-acetylisonicotinylhydrazide |
| 1-acetyl-2-isonicotinoylhydrazine |
| acetylisoniazid |
| n-acetyl-n'-isonicotinoylhydrazine |
| 4-pyridinecarboxylic acid, 2-acetylhydrazide |
| n'-acetylisonicotinohydrazide |
| hydrazine, 1-acetyl-2-isonicotinoyl- |
| brn 0154108 |
| CBDIVE_005562 |
| (n)1-acetylisoniazid |
| n-acetylisoniazid |
| 1078-38-2 |
| C07585 |
| 1-acetyl-2-isonicotinoyl-hydrazine |
| n'-acetylpyridine-4-carbohydrazide |
| isonicotinic acid n'-acetyl-hydrazide |
| AKOS001586427 |
| FT-0661273 |
| NCGC00245164-01 |
| HMS2469P12 |
| j42942uvun , |
| 4-22-00-00606 (beilstein handbook reference) |
| unii-j42942uvun |
| 2-acetylhydrazide-4-pyridinecarboxylic acid |
| CHEMBL1442231 |
| SCHEMBL1415953 |
| acetylisoniazide;n-monoacetylisoniazid; nsc 36084 |
| DTXSID1020013 |
| n-[(pyridin-4-yl)carbonyl]ethanehydrazonic acid |
| J-002022 |
| sr-01000389726 |
| SR-01000389726-1 |
| n-isonicotinoyl-n'-acetyl-hydrazin |
| Q27107456 |
| 4-ethylcatechol 100 microg/ml in acetonitrile |
| BS-25514 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " The anti-TB drugs of first choice were developed more than 4 decades ago and present several adverse effects, making the treatment of TB even more complicated and the development of new chemotherapeutics for this disease imperative." | ( New hydrazides derivatives of isoniazid against Mycobacterium tuberculosis: Higher potency and lower hepatocytotoxicity. Aiub, CAF; Araujo-Lima, CF; Boechat, N; Castelo-Branco, FS; Costa, TEMM; Costa-Lima, MM; de Lima, EC; Domingos, JLO; Felzenszwalb, I; Gomes, KM; Henriques, MG; Lourenço, MCS; Penido, C; Pinto, AC, 2018) | 0.48 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " The results suggested that the pharmacokinetic behavior of Iso in rats belonged to a 2-compartment model." | ( Effects of rifampicin on pharmacokinetics of isoniazid and its metabolite acetylhydrazine in rats. Cheng, WB; Li, D; Wang, ZY; Zhang, RL, 1992) | 0.28 |
| " No significant modification of the plasma pharmacokinetic profiles of isoniazid and acetylisoniazid was found." | ( A study of the effects of rifabutin on isoniazid pharmacokinetics and metabolism in healthy volunteers. Breda, M; Carpentieri, M; Efthymiopoulos, C; Pianezzola, E; Rimoldi, R; Sassella, D; Strolin Benedetti, M, 1992) | 0.51 |
| " This pharmacokinetic analysis, however, also shows that the apparent plasma half-life of acetylhydrazine is about five times longer than the plasma half-life of isoniazid, and thus repeated doses of isoniazid should lead to an accumulation of acetylhydrazine in the slowest acetylators in which the plasma half-life of acetylhydrazine is 20-plus hr." | ( Pharmacokinetics of the toxic hydrazino metabolites formed from isoniazid in humans. Lauterburg, BH; Mitchell, JR; Smith, CV; Todd, EL, 1985) | 0.27 |
| " There was a good linear relationship between pharmacokinetic parameters and the number of active NAT2 genes." | ( Gene dose effect of NAT2 variants on the pharmacokinetics of isoniazid and acetylisoniazid in healthy Chinese subjects. Bing, C; Jinhenga, L; Xiaomeia, C, 2011) | 0.6 |
| "Genetic variants in NAT2 are associated with pharmacokinetic variation of isoniazid, the cornerstone of antituberculosis treatment." | ( Full-gene sequencing analysis of NAT2 and its relationship with isoniazid pharmacokinetics in Venezuelan children with tuberculosis. Aarnoutse, RE; Coenen, MJ; de Waard, JH; García, JF; Hermans, PW; López, D; Schijvenaars, MM; Verhagen, LM, 2014) | 0.4 |
| "In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults." | ( Population pharmacokinetic analysis of isoniazid, acetylisoniazid, and isonicotinic acid in healthy volunteers. Chew, N; Hee, KH; Khoo, SH; Lee, LS; Seng, KY; Soon, GH, 2015) | 0.67 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "In order to solve the problem of poor patient compliance, attempts were made to prolong the bioavailability of antimycobacterial drugs after a single administration." | ( Sustained release of isoniazid in vivo from a single implant of a biodegradable polymer. Ashtekar, DR; Farhi, DC; Gangadharam, PR; Wise, DL, 1991) | 0.28 |
| "3 ml/hr/kg), bioavailability (0." | ( Temporal variations in the pharmacokinetics of isoniazid and N-acetylisoniazid in rats. Belanger, PM; Dore, FM; Labrecque, G; Lalande, M, ) | 0.37 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " INH and AINH plasma levels of 109 patients aged between four months to 87 years were measured, allowing dosage individualization." | ( [Application of a method of analysis using high performance liquid chromatography of isoniazid and acetylisoniazid to determine the phenotype of acetylation]. Leneveu, A; Miscoria, G; Roux, A; Walle, C, 1988) | 0.49 |
| "Male rats and rabbits were singly dosed with either 1-[14C]acetyl isoniazid (acetylisonicotinoylhydrazine, acetyl-INH, 200 mg/kg po) or 1-[14C]acetylhydrazine (50 or 100 mg/kg ip)." | ( Metabolism of [14C]acetylisoniazid and [14C]acetylhydrazine by the rat and rabbit. Thomas, BH; Whitehouse, LW; Zeitz, W, 1984) | 0.6 |
| " More extensive studies showed that over 99% of the urine samples collected within 18h of dosage with 6 mg INH would give positive results when tested for the presence of INA and INAG, and that doses of 2-6 mg INH could readily by incorporated into capsules or tablets and used as markers for monitoring the ingestion of the antituberculosis or antileprosy drugs dapsone, thiacetazone, ethionamide or prothionamide, or the antihypertensive oxprenolol." | ( An evaluation of the potential use of isoniazid, acetylisoniazid and isonicotinic acid for monitoring the self-administration of drugs. Downs, PA; Ellard, GA; Jenner, PJ, 1980) | 0.52 |
| " Clinically it is important to know to which genetic group the patient belongs because we may have to increase the dosage for the rapid acetylators to achieve the desired therapeutic effect, while we may have to reduce the dosage for slow acetylators in whom the incidence of side effect is high." | ( [Testing for heterogeneity in genetic polymorphism of N-acetylation using isoniazid by metameters--probit, logit, and arcsine transformation]. Katayama, T; Kohno, H; Mori, M, 1993) | 0.29 |
| " We determined peak concentration ranges for each drug and acetylisoniazid/isoniazid and 25-desacetylrifampicin/rifampicin ratios by analyzing 2-h post-dose samples in patients treated with standard dosing as a first-line treatment." | ( Simultaneous determination of first-line anti-tuberculosis drugs and their major metabolic ratios by liquid chromatography/tandem mass spectrometry. Jun, SH; Kim, JQ; Lee, JH; Park, KU; Song, J; Song, SH; Yoon, Y, 2007) | 0.58 |
| " Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤ Cmax ≤ 6 mg/liter) irrespective of the acetylator class." | ( Population pharmacokinetic analysis of isoniazid, acetylisoniazid, and isonicotinic acid in healthy volunteers. Chew, N; Hee, KH; Khoo, SH; Lee, LS; Seng, KY; Soon, GH, 2015) | 0.67 |
| Role | Description |
|---|---|
| metabolite | Any intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| carbohydrazide | A hydrazide consisting of hydrazine carrying one or more carboacyl groups. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Chain A, Beta-lactamase | Escherichia coli K-12 | Potency | 0.7079 | 0.0447 | 17.8581 | 100.0000 | AID485294 |
| cellular tumor antigen p53 isoform a | Homo sapiens (human) | Potency | 0.0891 | 0.3162 | 12.4435 | 31.6228 | AID904 |
| chromobox protein homolog 1 | Homo sapiens (human) | Potency | 89.1251 | 0.0060 | 26.1688 | 89.1251 | AID540317 |
| peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 | Homo sapiens (human) | Potency | 84.9214 | 0.4256 | 12.0591 | 28.1838 | AID504891 |
| Guanine nucleotide-binding protein G | Homo sapiens (human) | Potency | 31.6228 | 1.9953 | 25.5327 | 50.1187 | AID624287 |
| Inositol monophosphatase 1 | Rattus norvegicus (Norway rat) | Potency | 0.3981 | 1.0000 | 10.4756 | 28.1838 | AID901 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| negative regulation of inflammatory response to antigenic stimulus | Guanine nucleotide-binding protein G | Homo sapiens (human) |
| renal water homeostasis | Guanine nucleotide-binding protein G | Homo sapiens (human) |
| G protein-coupled receptor signaling pathway | Guanine nucleotide-binding protein G | Homo sapiens (human) |
| regulation of insulin secretion | Guanine nucleotide-binding protein G | Homo sapiens (human) |
| cellular response to glucagon stimulus | Guanine nucleotide-binding protein G | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| G protein activity | Guanine nucleotide-binding protein G | Homo sapiens (human) |
| adenylate cyclase activator activity | Guanine nucleotide-binding protein G | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| plasma membrane | Guanine nucleotide-binding protein G | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID1745845 | Primary qHTS for Inhibitors of ATXN expression | |||
| AID504810 | Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign | 2010 | Endocrinology, Jul, Volume: 151, Issue:7 | A small molecule inverse agonist for the human thyroid-stimulating hormone receptor. |
| AID504812 | Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign | 2010 | Endocrinology, Jul, Volume: 151, Issue:7 | A small molecule inverse agonist for the human thyroid-stimulating hormone receptor. |
| AID651635 | Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression | |||
| AID1143485 | Antitubercular activity against katG-deficient isoniazid-resistant Mycobacterium tuberculosis H37Rv ATCC 27294 by BACTEC 960 assay | 2014 | European journal of medicinal chemistry, Jun-23, Volume: 81 | Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity. |
| AID1059231 | Antitubercular activity against Mycobacterium tuberculosis | 2013 | European journal of medicinal chemistry, , Volume: 70 | Comparison of Multiple Linear Regressions and Neural Networks based QSAR models for the design of new antitubercular compounds. |
| AID1143484 | Antitubercular activity against Mycobacterium tuberculosis H37Rv clinical isolate harboring katG S315T mutant by BACTEC 960 assay | 2014 | European journal of medicinal chemistry, Jun-23, Volume: 81 | Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity. |
| AID1143488 | Cytotoxicity against african green monkey Vero cells after 48 hrs by MTT assay | 2014 | European journal of medicinal chemistry, Jun-23, Volume: 81 | Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity. |
| AID1143489 | Selectivity index, ratio of IC50 for african green monkey Vero cells to MIC for Mycobacterium tuberculosis H37Rv ATCC 27294 | 2014 | European journal of medicinal chemistry, Jun-23, Volume: 81 | Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity. |
| AID1381931 | Antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 after 5 days by microplate alamar blue assay | 2018 | European journal of medicinal chemistry, Feb-25, Volume: 146 | New hydrazides derivatives of isoniazid against Mycobacterium tuberculosis: Higher potency and lower hepatocytotoxicity. |
| AID1143483 | Antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 by BACTEC 960 assay | 2014 | European journal of medicinal chemistry, Jun-23, Volume: 81 | Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity. |
| AID1059234 | Lipophilicity, log P of the compound | 2013 | European journal of medicinal chemistry, , Volume: 70 | Comparison of Multiple Linear Regressions and Neural Networks based QSAR models for the design of new antitubercular compounds. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 25 (44.64) | 18.7374 |
| 1990's | 10 (17.86) | 18.2507 |
| 2000's | 6 (10.71) | 29.6817 |
| 2010's | 14 (25.00) | 24.3611 |
| 2020's | 1 (1.79) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.
| This Compound (23.49) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 3 (4.84%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 59 (95.16%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||