title: Azatyrosinamides: novel RAS-related anticancer agents.
abstract: BACKGROUND
  We previously reported on the design and synthesis of novel azatyrosinamide derivatives selective for ras-transformed NIH3T3 cells and with improved toxicity over azatyrosine. This study was aimed at investigating the mechanism of action and the antitumour activity of these compounds in ras-transformed cells.
  
  
  METHODS
  Nine azatyrosinamides were previously screened for anticancer activity in both wild-type and ras-transformed NIH3T3 cells; the most active compounds were further tested in vitro and in vivo.
  
  
  RESULTS
  HPW98-1 and HPW98-2 induced formation of apoptotic bodies in ras-transformed NIH3T3 cells in vitro and inhibited anchorage-independent growth. Excess tyrosine reduced the cytotoxic effect of azatyrosine, but not of HPW98-1 and HPW98-2. HPW98-1 reduced vascular endothelial growth factor-mediated angiogenesis in a Matrigel plug assay and attenuated growth of a ras-transformed NIH3T3 xenograft and a human SW620 xenograft.
  
  
  CONCLUSIONS
  Our results support the continued study of HPW98-1 for its potential use in the treatment of RAS-related cancers.
authors: Professor of Taipei Medical University College of Pharmacy. 250 Wu-Hsing St., Taipei, Taiwan 110, ROC.
authors: Chun-Li
authors: CL
authors: Wang
authors: On
authors: O
authors: Lee
authors: Chiu-Fen
authors: CF
authors: Huang
authors: Eric I-Chian
authors: EI
authors: Li
authors: Che-Ming
authors: CM
authors: Teng
authors: Shiow-Lin
authors: SL
authors: Pan
authors: Jang-Feng
authors: JF
authors: Lian
authors: Feng-Shou
authors: FS
authors: Chang
authors: Jing-Ping
authors: JP
authors: Liou
authors: Hui-Po
authors: HP
authors: Wang
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C011870:beta-(5-hydroxy-2-pyridyl)alanine; D000409:Alanine