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The 2.3A Crystal Structure of Humanized Xenopus MDM2 with RO5545353The 2.3A Crystal Structure of Humanized Xenopus MDM2 with RO5545353
Structural highlights
FunctionMDM2_XENLA E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity). Publication Abstract from PubMedThe development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents a novel approach for cancer treatment. In a previous communication, the efforts leading to the identification of a non-imidazoline MDM2 inhibitor, RG7388, was disclosed and revealed the desirable in vitro and in vivo pharmacological properties that this class of pyrrolidine-based inhibitors possesses. Given this richness and the critical need for a wide variety of chemical structures to ensure success in the clinic, research was expanded to evaluate additional derivatives. Here we report two new potent, selective, and orally active p53-MDM2 antagonists, RO5353 and RO2468, as follow-ups with promising potential for clinical development. Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development.,Zhang Z, Chu XJ, Liu JJ, Ding Q, Zhang J, Bartkovitz D, Jiang N, Karnachi P, So SS, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev L, Graves B ACS Med Chem Lett. 2013 Dec 29;5(2):124-7. doi: 10.1021/ml400359z. eCollection, 2014 Feb 13. PMID:24900784[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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