title: Comparative preclinical toxicology and pharmacology of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) in vitro and in rodents and primates.
abstract: 4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) is being evaluated for its anticancer activities. Acute, subacute and chronic oral, dermal, opthalmic and dermal LD50 and acceptance studies in adult mice, rats, rabbits and monkeys demonstrated some vomiting at 5 g/kg doses in monkeys but otherwise no unacceptable toxicities. In vitro, T.I. for A-007 were calculated using murine bone marrow GM-CFC and human cancer cell lines. A relative oral bioavailability factor of 2% was calculated for rats and monkeys for plasma A-007. Non-compartmental pharmacokinetic analysis suggests enterohepatic circulation. Plasma A-007 could not be detected after applying a 0.25% gel topically. Generally, A-007 is well tolerated.
authors.affiliation: DEKK-TEC, Inc., New Orleans, Louisiana, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Morgan
authors.forename: A H
authors.initials: AH
authors.lastname: Rodgers
authors.forename: D
authors.initials: D
authors.lastname: Fan
authors.forename: K
authors.initials: K
authors.lastname: Soike
authors.forename: M
authors.initials: M
authors.lastname: Ratterree
authors.forename: B W
authors.initials: BW
authors.lastname: Sartin
authors.forename: T J
authors.initials: TJ
authors.lastname: Harrison
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D001854:Bone Marrow Cells; D001943:Breast Neoplasms; D015197:Carcinogenicity Tests; D002522:Chlorocebus aethiops; D003110:Colonic Neoplasms; D004305:Dose-Response Relationship, Drug; D015817:Eye Infections / Q000139:chemically induced; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000493:pharmacokinetics / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007680:Kidney Neoplasms; D008175:Lung Neoplasms; D008297:Male; D008545:Melanoma; D051379:Mice; D008815:Mice, Inbred Strains; D010636:Phenols / Q000493:pharmacokinetics / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D012871:Skin Diseases / Q000139:chemically induced; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: C097674:4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone; D000970:Antineoplastic Agents; D006835:Hydrazones; D010636:Phenols