| First Author | Kung AL | Year | 2004 |
| Journal | Cancer Cell | Volume | 6 |
| Issue | 1 | Pages | 33-43 |
| PubMed ID | 15261140 | Mgi Jnum | J:156233 |
| Mgi Id | MGI:4419081 | Doi | 10.1016/j.ccr.2004.06.009 |
| Citation | Kung AL, et al. (2004) Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell 6(1):33-43 |
| abstractText | Homeostasis under hypoxic conditions is maintained through a coordinated transcriptional response mediated by the hypoxia-inducible factor (HIF) pathway and requires coactivation by the CBP and p300 transcriptional coactivators. Through a target-based high-throughput screen, we identified chetomin as a disrupter of HIF binding to p300. At a molecular level, chetomin disrupts the structure of the CH1 domain of p300 and precludes its interaction with HIF, thereby attenuating hypoxia-inducible transcription. Systemic administration of chetomin inhibited hypoxia-inducible transcription within tumors and inhibited tumor growth. These results demonstrate a therapeutic window for pharmacological attenuation of HIF activity and further establish the feasibility of disrupting a signal transduction pathway by targeting the function of a transcriptional coactivator with a small molecule. |
