title: Optimization of naphthalimide-imidazoacridone with potent antitumor activity leading to clinical candidate (HKH40A, RTA 502).
abstract: Unsymmetrical bifunctional antitumor agent WMC79 was further optimized to generate compound 7b that not only inhibited the growth of many tumor cell lines, but caused rapid apoptosis. Unlike the parent compound, 7b is toxic to both p53 positive and negative cancer cells. It has potent in vivo activity against xenografts of human colon and pancreatic tumors in athymic mice.
authors.affiliation: Molecular Aspects of Drug Design Section, Structural Biophysics Laboratory, Center for Cancer Research, NCI-Frederick, Frederick, MD 21702, USA.
authors.forename: Humcha K
authors.initials: HK
authors.lastname: Hariprakasha
authors.forename: Teresa
authors.initials: T
authors.lastname: Kosakowska-Cholody
authors.forename: Colin
authors.initials: C
authors.lastname: Meyer
authors.forename: Wieslaw M
authors.initials: WM
authors.lastname: Cholody
authors.forename: Sherman F
authors.initials: SF
authors.lastname: Stinson
authors.forename: Nadya I
authors.initials: NI
authors.lastname: Tarasova
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Michejda
mesh_terms: D054831:Acridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053644:Naphthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D009368:Neoplasm Transplantation; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D054831:Acridones; D000970:Antineoplastic Agents; D053644:Naphthalimides; C525457:RTA 502; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53