Download MendeleyATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines.
Zask, A., Verheijen, J.C., Curran, K., Kaplan, J., Richard, D.J., Nowak, P., Malwitz, D.J., Brooijmans, N., Bard, J., Svenson, K., Lucas, J., Toral-Barza, L., Zhang, W.G., Hollander, I., Gibbons, J.J., Abraham, R.T., Ayral-Kaloustian, S., Mansour, T.S., Yu, K.(2009) J Med Chem 52: 5013-5016
- PubMed: 19645448
- DOI: https://doi.org/10.1021/jm900851f
- Primary Citation of Related Structures:
3IBE - PubMed Abstract:
The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.
Organizational Affiliation:
Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. zaska@wyeth.com
