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Repositioning Candidate Details

Candidate ID: R0276
Source ID: DB00951
Source Type: approved; investigational
Compound Type: small molecule
Compound Name: Isoniazid
Synonyms:
Molecular Formula: C6H7N3O
SMILES: NNC(=O)C1=CC=NC=C1
Structure:
DrugBank Description: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.
CAS Number: 54-85-3
Molecular Weight: 137.1393
DrugBank Indication: For the treatment of all forms of tuberculosis in which organisms are susceptible.
DrugBank Pharmacology: Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically <i>M. tuberculosis</i>, <i>M. bovis</i> and <i>M. kansasii</i>. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal when mycobacteria grow rapidly and bacteriostatic when they grow slowly.
DrugBank MoA: Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular <i>Mycobacterium tuberculosis</i> organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from <i>Mycobacterium tuberculosis</i>, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.
Targets: Catalase-peroxidase; Enoyl-[acyl-carrier-protein] reductase [NADH]; Cytochrome P450 2C8; Cytochrome P450 1A2; Cytochrome P450 3A4; Cytochrome P450 2C19; Dihydrofolate reductase
Inclusion Criteria: