title: A novel camptothecin analog with enhanced antitumor activity.
abstract: BACKGROUND
  The use of camptothecin (CPT) derivatives is limited by severe toxicity associated with the instability of their chemical structure. We have developed a stable CPT derivative (CPT417) and have investigated its biological activity in comparison to the currently used CPT analogs.
  
  
  METHODS
  The anticancer effects of CPT417 were assessed in vitro, with glioblastoma and colon cancer cell lines, and in vivo with mice bearing mammary adenocarcinoma tumors implanted subcutaneously in the flank. Cytotoxicity was assessed using vital dye exclusion, timelapse microscopy and colony formation.
  
  
  RESULTS
  CPT417 and topotecan inhibited glioblastoma cell growth at comparable levels and both compounds inhibited clonogenicity of colon cancer cells more effectively than irinotecan. CPT417 showed a much greater inhibition of mammary tumor growth compared to topotecan, both by intraperitoneal and oral administration.
  
  
  CONCLUSIONS
  CPT417 shows dramatically reduced toxicity and an enhanced antitumor activity compared to topotecan.
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Garret
authors.initials: G
authors.lastname: Yount
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Brian
authors.initials: B
authors.lastname: Wong
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Wang
authors.forename: Li-Xi
authors.initials: LX
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D019772:Topotecan / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C524373:CPT417; D019772:Topotecan; D002166:Camptothecin