| Structural highlights
Function
MDM2_XENLA E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).
Publication Abstract from PubMed
The field of small-molecule inhibitors of protein-protein interactions is rapidly advancing and the specific area of inhibitors of the p53/MDM2 interaction is a prime example. Several groups have published on this topic and multiple compounds are in various stages of clinical development. Building on the strength of the discovery of RG7112, a Nutlin imidazoline-based compound, and RG7388, a pyrrolidine-based compound, we have developed additional scaffolds that provide opportunities for future development. Here, we report the discovery and optimization of a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitors, culminating in RO8994.
Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy.,Zhang Z, Ding Q, Liu JJ, Zhang J, Jiang N, Chu XJ, Bartkovitz D, Luk KC, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B Bioorg Med Chem. 2014 Jun 11. pii: S0968-0896(14)00431-3. doi:, 10.1016/j.bmc.2014.05.072. PMID:24997575[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Z, Ding Q, Liu JJ, Zhang J, Jiang N, Chu XJ, Bartkovitz D, Luk KC, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B. Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy. Bioorg Med Chem. 2014 Jun 11. pii: S0968-0896(14)00431-3. doi:, 10.1016/j.bmc.2014.05.072. PMID:24997575 doi:http://dx.doi.org/10.1016/j.bmc.2014.05.072
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