2. Academic Validation
  3. Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development

Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development

  • ACS Med Chem Lett. 2013 Dec 29;5(2):124-7. doi: 10.1021/ml400359z.
Zhuming Zhang 1,  Xin-Jie Chu 1,  Jin-Jun Liu 1,  Qingjie Ding 1,  Jing Zhang 1,  David Bartkovitz 1,  Nan Jiang 1,  Prabha Karnachi 1,  Sung-Sau So 1,  Christian Tovar 1,  Zoran M Filipovic 1,  Brian Higgins 1,  Kelli Glenn 1,  Kathryn Packman 1,  Lyubomir Vassilev 1,  Bradford Graves 1
Affiliations

Affiliation

  • 1 Discovery Chemistry, Discovery Technologies, Discovery Oncology, and Non-Clinical Development, Roche Pharma Research, Hoffmann-La Roche, Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
PMID: 24900784 DOI: 10.1021/ml400359z
Abstract

The 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.

Keywords

MDM2; apoptosis; cancer; p53; small molecule; wild-type.

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