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Compound Detail

CHEMBL64

ISONIAZID
💊 Approved Drug
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💊 Approved Drug
NNC(=O)c1ccncc1

Basic Information

ChEMBL ID CHEMBL64
Name ISONIAZID
Phase Approved
Structure Type MOL
InChI Key QRXWMOHMRWLFEY-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Armazid Armazide Atcotibine Cedin Cotinazin Dianicotyl Dow-isoniazid Eralon Ertuban Hidrasonil Hydrazid Hyzyd +18 more
15
Targets
70
Activities
3
Assay Types
30
PK Parameters
20
Publications
30
Known Names
12
Indications
1
Mechanisms

Molecular Properties

137.1
MW (Da)
-0.31
ALogP
3
HBA
2
HBD
68.0
PSA (Ų)
0.32
QED
0
Ro5 Violations
1
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1952
Availability Prescription
Chirality Achiral

Routes of Administration

Oral Parenteral

Flags

Black Box Warning Natural Product

Extended Properties

Molecular Formula C6H7N3O
MW 137.14
Aromatic Rings 1
Heavy Atoms 10
NP-Likeness -1.62

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Enoyl-[acyl-carrier-protein] reductase inhibitor INHIBITOR Enoyl-[acyl-carrier-protein] reductase [NADH]

Indications

HIV Infections Silicosis Tuberculosis Tuberculosis, Pulmonary Meningitis Acquired Immunodeficiency Syndrome Diabetic Foot Tuberculosis, Multidrug-Resistant Tuberculosis, Multidrug-Resistant Ulcer Melanoma Osteomyelitis

ATC Classification

J04AC01
isoniazid
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIMYCOBACTERIALS
J04AC51
isoniazid, combinations
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIMYCOBACTERIALS

Drug Warnings

Black Box Warning
hepatotoxicity
Country: United States
Black Box Warning
gastrointestinal toxicity
Country: United States

Activity Summary

IC50 58 meas. best 7.4
Ki 9 meas. best 9.12
EC50 3 meas. best 6.89

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Enoyl-[acyl-carrier-protein] reductase [NADH]
CHEMBL1849
Ki 9.12 8.46 0.8 2
Dihydrofolate reductase
CHEMBL6065
Ki 9.0 9.0 1.0 1
Mycobacterium tuberculosis
CHEMBL360
IC50 7.4 6.6433 40.0 27
Mycobacterium tuberculosis
CHEMBL360
EC50 6.89 6.7867 130.0 3
NON-PROTEIN TARGET
CHEMBL3879801
IC50 5.58 5.58 2600.0 1
Mycobacterium tuberculosis variant bovis
CHEMBL613086
IC50 5.52 5.52 3000.0 1
Unchecked
CHEMBL612545
IC50 5.41 4.942 3900.0 5
Myeloperoxidase
CHEMBL2439
IC50 5.33 5.315 4700.0 2
Mycolicibacterium smegmatis
CHEMBL613088
IC50 5.11 4.8325 7800.0 4
Enoyl-[acyl-carrier-protein] reductase [NADH]
CHEMBL1849
IC50 5.08 5.08 8290.0 1
Cytochrome P450 2C19
CHEMBL3622
Ki 5.0 5.0 10000.0 1
No relevant target
CHEMBL2362975
IC50 4.64 4.64 22900.0 1
Cytochrome P450 3A4
CHEMBL340
Ki 4.44 4.44 36000.0 1
Vero
CHEMBL391
IC50 4.4 4.4 39800.0 1
Cytochrome P450 1A2
CHEMBL3356
Ki 4.25 4.25 56000.0 1
Cytochrome P450 2A6
CHEMBL5282
Ki 4.22 4.22 60000.0 1
THP-1
CHEMBL614245
IC50 4.0 4.0 100000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 22900.0 ng.hr.mL-1 Homo sapiens
AUC 4550.0 ng.hr.mL-1 Mus musculus
AUC 18.22 - Cavia porcellus
AUC 16640.0 ng.hr.mL-1 Mus musculus
AUC 55340.0 ng.hr.mL-1 Mus musculus
AUC 197090.0 ng.hr.mL-1 Rattus norvegicus
AUC 684000.0 ng.hr.mL-1 Rattus norvegicus
AUC 10520.0 ng.hr.mL-1 Mycobacterium tuberculosis
AUC 19780.0 ng.hr.mL-1 Homo sapiens
AUC 42240.0 ng.hr.mL-1 Homo sapiens
AUC 42190.0 ng.hr.mL-1 Homo sapiens
AUC 10350.0 ng.hr.mL-1 Homo sapiens
AUC 38050.0 ng.hr.mL-1 Homo sapiens
AUC 16340.0 ng.hr.mL-1 Homo sapiens
CL 7.4 mL.min-1.kg-1 Homo sapiens
CL 4.43 ml/hr Mus musculus
CL 63.9 ml/hr Mus musculus
CL 0.21 mL.min-1.kg-1 Rattus norvegicus
CL 16.07 L/hr Homo sapiens
CL 7.79 L/hr Homo sapiens
CL 7.4 L/hr Homo sapiens
CL 30.05 L/hr Homo sapiens
CL 8.03 L/hr Homo sapiens
CL 19.17 L/hr Homo sapiens
Cmax 280005833.45 nM Mus musculus
Cmax 32813.18 nM Homo sapiens
Cmax 22312.96 nM Mus musculus
Cmax 1.09 ug/10^6 cells Homo sapiens
Cmax 1.31 ug/10^6 cells Homo sapiens
Cmax 0.56 ug Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Enoyl-[acyl-carrier-protein] reductase [NADH] Ki = 0.75 nM 9.12 Binding affinity to wild type Mycobacterium tuberculosis InhA assessed as inhibi... 36435016
Dihydrofolate reductase Ki = 1.0 nM 9.0 Inhibition of Mycobacterium tuberculosis dihydrofolate reductase 20566771
Enoyl-[acyl-carrier-protein] reductase [NADH] Ki = 16.0 nM 7.8 Binding affinity to wild type Mycobacterium tuberculosis InhA assessed as inhibi... 36435016
Mycobacterium tuberculosis IC50 = 40.0 nM 7.4 Antimycobacterial activity against Mycobacterium tuberculosis H37Rv after 6 days... 24631899
Mycobacterium tuberculosis IC50 = 70.0 nM 7.16 Antimicrobial activity against Mycobacterium tuberculosis H37Rv in GASTD medium ... 21940166
Mycobacterium tuberculosis IC50 = 90.0 nM 7.05 Antimicrobial activity against Mycobacterium tuberculosis H37Rv in GASTD medium ... 21940166
Mycobacterium tuberculosis IC50 = 100.0 nM 7.0 Antimicrobial activity against Mycobacterium tuberculosis H37Rv ATCC 27294 incub... 27025343
Mycobacterium tuberculosis IC50 = 100.0 nM 7.0 Antimycobacterial activity activity against Mycobacterium tuberculosis H37Rv aft... 31703818
Mycobacterium tuberculosis IC50 = 100.0 nM 7.0 Antibacterial activity against Mycobacterium tuberculosis H37Ra ATCC2517 assesse... 33248851
Mycobacterium tuberculosis IC50 = 110.0 nM 6.96 Antimycobacterial activity against Mycobacterium tuberculosis H37Ra lux incubate... 31376569
Mycobacterium tuberculosis IC50 = 120.0 nM 6.92 Antimycobacterial activity against Mycobacterium tuberculosis H37Rv 29202408
Mycobacterium tuberculosis EC50 = 130.0 nM 6.89 Antitubercular activity against Mycobacterium tuberculosis H37Rv by BacTiter-Gl ... 23352268
Mycobacterium tuberculosis IC50 = 131.0 nM 6.88 Antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 afte... 28993106
Mycobacterium tuberculosis IC50 = 150.0 nM 6.82 Antitubercular activity against Mycobacterium tuberculosis H37Rv RIF-R1 harborin... 27437078
Mycobacterium tuberculosis IC50 = 180.0 nM 6.75 Antimicrobial activity against Mycobacterium tuberculosis H37Rv by Alamar blue a... 28552337
Mycobacterium tuberculosis IC50 = 180.0 nM 6.75 Antimycobacterial activity against Mycobacterium tuberculosis H37Rv assessed as ... 27687968
Mycobacterium tuberculosis EC50 = 180.0 nM 6.75 Antimycobacterial activity against Mycobacterium tuberculosis H37Rv assessed as ... 24472146
Mycobacterium tuberculosis IC50 = 180.0 nM 6.75 Antimycobacterial activity against Mycobacterium tuberculosis H37Rv assessed as ... 25129868
Mycobacterium tuberculosis IC50 = 180.0 nM 6.75 Antimicrobial activity against Mycobacterium tuberculosis H37Rv after 7 days by ... 24412719
Mycobacterium tuberculosis EC50 = 190.0 nM 6.72 Antitubercular activity against Mycobacterium tuberculosis H37Rv by microdilutio... 23352268

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 1398
- 10.6019/CHEMBL3885881 Rattus norvegicus 555
4851320 10.1002/jps.2600630804 ADMET 104
17438054 10.1128/aac.00086-07 Mycobacterium tuberculosis 37
33826327 10.1021/acs.jmedchem.0c01833 Mycobacterium tuberculosis 36
21980963 10.1515/dmdi.2011.016 Homo sapiens 30
20566771 10.1128/aac.00453-10 Mycolicibacterium smegmatis 28
18378710 10.1128/aac.01486-07 Mycobacterium tuberculosis 23
20516287 10.1128/aac.00287-10 Mycobacterium tuberculosis 21
22088956 10.1016/j.ejmech.2011.10.054 Mycobacterium tuberculosis 20
24967731 10.1021/jm500833f Mycobacterium tuberculosis 20
26280920 10.1016/j.ejmech.2015.07.039 Mycobacterium tuberculosis 20
24224794 10.1021/np400145u Mycobacterium tuberculosis 19
26900657 10.1016/j.ejmech.2016.02.008 Mycobacterium tuberculosis 18
29407978 10.1016/j.ejmech.2018.01.071 Salmonella typhimurium 18
16472241 10.2174/1570163043334794 Hepatotoxicity 18
- 10.1039/C5MD00178A Mycobacterium tuberculosis 17
20008778 10.1128/aac.00964-09 Mycobacterium tuberculosis 16
10879539 10.1038/35016103 Mycobacterium tuberculosis 16
17132069 10.1371/journal.pmed.0030466 Mycobacterium tuberculosis 16

Data from ChEMBL 36 via Core Engine