| Autor: |
Grasberger, B. L., Lu, T., Schubert, C., Parks, D. J., Carver, T. E., Koblish, H. K., Cummings, M. D., LaFrance, L. V., Milkiewicz, K. L., Calvo, R. R., Maguire, D., Lattanze, J., Franks, C. F., Zhao, S., Ramachandren, K., Bylebyl, G. R., Zhang, M., Manthey, C. L., Petrella, E. C., Pantoliano, M. W., Deckman, I. C., Spurlino, J. C., Maroney, A. C., Tomczuk, B. E., Molloy, C. J., Bone, R. F. |
| Zdroj: |
Journal of Medicinal Chemistry; February 2005, Vol. 48 Issue: 4 p909-912, 4p |
| Abstrakt: |
HDM2 binds to an α-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2−p53 interaction. The X-ray crystal structure of improved antagonists bound to HDM2 reveals their α-helix mimetic properties. These optimized molecules increase the transcription of p53 target genes and decrease proliferation of tumor cells expressing wild-type p53. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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