Fabimycin

Fabimycin is a FabI inhibitor with potent antibacterial activity against gram-negative bacteria. Fabimycin is effective against drug-resistant gram-negative Infections in vivo[1].

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> Bacterial

Fabimycin shows outstanding activity against S. aureus (MIC: 4 ng/mL), E. coli MG1655 (MIC: 2 μg/mL)[1]. Fabimycin (4 μg/mL) inhibits 90% of the strainsagainst a panel of 100 K. pneumoniae clinical isolates[1]. Fabimycin enhances the stability of the enzyme-inhibitor complex significantly more than the less active enantiomer in both E. coli and A. baumannii versions of FabI[1].

Fabimycin (Intramuscular injection, 5 mg/kg, 2 and 7 h postinfection) shows significant great reduction of bacterial burden in Neutropenic mouse thigh infection initiated in CD-1 mice with S. aureus[1]. Fabimycin (intraperitoneal injection) is tolerated in mice with an MTD of >200 mg/kg[1]. Animal Model: Acute pneumonia murine or neutropenic mouse thigh infection model, initiated in CD-1 mice with A. baumannii[1] Dosage: 50 mg/kg Administration: Intramuscular injection, 4, 23, and 41 h postinfection (pneumonia model), or 2, 6, and 11 h postinfection (thigh infection) Result: Achieved a >3‑fold decrease in log(CFU/lung) and >2-fold decrease log(CFU/thigh) relative to the vehicle. Animal Model: Urinary tract infections (UTIs) model (C3H/HeJ mice)[1] Dosage: 33.3 mg/kg Administration: Intravenous injection, three times a day, Result: Achieved 3.0, 2.8, 2.9, and 1.9 log10 reductions in bacterial load relative to the vehicle in the spleen, bladder, liver, and kidney tissues, respectively. Animal Model: Neutropenic female BALB/c mice infected with drug-resistant A. baumannii (pharmacokinetic assay)[1] Dosage: 20, 50, 75, 100 mg/kg Administration: Intravenous injection, for a single dose Result: Pharmacokinetic profile of Fabimycin. pharmacokinetic property AUClast (h•μg/mL) T1/2 (h) CL (mL/min/kg) Cmax (μg/mL) 100 mg/kg 69.8 1.4 23.5 47.3 75 mg/kg 45.4 1.4 26.9 34.6

[1]. Erica N. Parker, et al. An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections. DOI: 10.1021/acscentsci.2c00598.