4,4'-Dihydroxybenzophenone- 2,4-dinitrophenylhydrazone (A-007) has demonstrated antiestrogenic and cytotoxic activities in vitro and in vivo. The long term objectives of this project are to obtain the necessary preclinical information to file an IND and initiate clinical studies with A-007 in advanced breast cancer. In this application, murine tumor models (B-16, mammary 16/C and human MDA-MB-435 breast cancer xenograft) and African green monkey studies will address animal sensitivities and toxicities. Pharmacokinetic and chronic dosing studies for oral A-007 in rats will be completed. All A-007 metabolites will be evaluated in vitro (cancer cell lines and GM-CFC) and in vivo (immature rat). Extensive quality control validations of all analytical and preparative procedures necessary to register an IND will be finalized. In the second year of the study, an IND will be submitted and a Phase I study for topical A-007 in advanced cutaneous metastasis from breast cancer will be initiated.
| Morgan, L R; Rodgers, A H; Fan, D et al. (1997) Comparative preclinical toxicology and pharmacology of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) in vitro and in rodents and primates. In Vivo 11:29-37 |
| Rodgers, A H; Subramanian, S; Morgan Jr, L R (1995) High-performance liquid chromatographic determination of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone in plasma. J Chromatogr B Biomed Appl 670:365-8 |
