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lüll Small molecule-mediated anti-cancer therapy via hypoxia-inducible factor-1 blockade Macpherson GR; Figg WDCancer Biol Ther 2004[Jun]; 3 (6): 503-4Despite reservations regarding potential toxicities, small molecule-mediated blockade of the hypoxia-inducible factor-1 transcription factor has emerged as a viable anti-cancer strategy in vivo. Recent experiments by Welsh et al. revealed unprecedented anti-tumor responses of various aggressive solid tumors to the HIF-1-inhibitory small molecule drug PX-478. Compared with other anti-cancer drugs, PX-478 had markedly improved regression, growth delay and log10 cell kill profiles, particularly against large tumors that are normally refractory to small molecule drug therapy. Importantly, pharmacokinetic and toxicity profiles were within acceptable limits, providing rationale for the clinical development of HIF-1 inhibitors in general. Though the mechanism of action for PX-478 is not completely understood, inhibition of glycolysis rather than angiogenesis appeared to be the primary mode of anti-cancer activity.|Animals[MESH]|Antineoplastic Agents/*therapeutic use[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1, alpha Subunit[MESH]|Mustard Compounds/*therapeutic use[MESH]|Neoplasms/*drug therapy[MESH]|Phenylpropionates/*therapeutic use[MESH]|Transcription Factors/*antagonists & inhibitors[MESH] |