Disease relevance of AT-4140

• In vitro activity of AT-4140 against quinolone- and methicillin-resistant Staphylococcus aureus [1].
• AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli [2].
• We tested the activity of the new fluoroquinolone sparfloxacin (CI-978; AT 4140) against 30 strains of Mycobacterium avium complex (MAC) isolated from patients with acquired immune deficiency syndrome [3].
• AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis [2].
• AT-4140 showed good oral efficacy against systemic infections with Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa in mice [4].

High impact information on AT-4140

• Compound 36k [named sparfloxacin, originally AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-7-(cis-3,5-dimethyl-1-piperazinyl)- 4(1H)-oxoquinoline-3-carboxylic acid] was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent [5].
• The pharmacokinetics of AT-4140 may be characterized by its good tissue penetration and its long half-life in plasma and tissues [6].
• The oral bioavailability of AT-4140 calculated from the ratio of the areas under the concentration-time curve after oral and intravenous administration was 77% in dogs [6].
• However, a number of newer fluoroquinolones (AT-4140, OPC-17100, OPC-17066, PD-117596, PD-124816, PD-127391, and WIN-57273), all containing a cyclopropyl group at R-1 and, with the exception of WIN-57273, either a halogen or methyl group at R-8, were more active than ofloxacin in vitro [7].
• The potencies of AT-4140 against gram-positive organisms, glucose nonfermenters, anaerobes, Mycoplasma spp., Chlamydia spp., and Mycobacterium spp. were generally higher than those of the quinolones with which AT-4140 was compared [4].

Chemical compound and disease context of AT-4140

• AM-1091, AT-4140 and T-3262 are still in early phases of development and show improved activity against Gram-positive bacteria [8].

Biological context of AT-4140

• Pharmacokinetics of a novel quinolone, AT-4140, in animals [6].

Associations of AT-4140 with other chemical compounds

• Comparative in vitro activities of sparfloxacin (CI-978; AT-4140) and other antimicrobial agents against staphylococci, enterococci, and respiratory tract pathogens [9].

Analytical, diagnostic and therapeutic context of AT-4140

• Disposition and metabolism of [carbonyl-14C]sparfloxacin SPFX, 5-amino-1-cyclopropyl-7-(cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro- 1,4-dihydro-4-oxoquinoline-3-carboxylic acid, AT-4140; CAS 110871-86-8), a novel antimicrobial quinolone, were studied in rats mainly after oral administration at 10 mg/kg [10].

References