St. Jude Children's Research Hospital

Leiden University Medical Center

Flanders Interuniversity Institute for Biotechnology

Universiteit Gent

Vib Vzw and Universiteit Gent

Michael Dyer

Jaeki Min

Jean-Christophe Marine

Nagakumar Bharatham

Brandon M Young

R Kiplin Guy

Richard Kriwacki

Antonio Ferreira

Yiqun Zhang

Lie Min

Kristin Finch

Donald Bashford

Aart Gerrit Jochemsen

Grace Roy-Appa

R Kip Guy

Fangyi Zhu

Grace Royappa

Anthony Ferreira

The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Aryl-substituted imidazoles

It has now been found that the p53 pathway is inactivated in ocular cancers such as retinoblastoma. As such, the present invention is a method for inducing ocular cancer cell death using a p53 activator. In particular embodiments, the p53 activator blocks the interaction between DM2 or DMX and p53. As the p53 activator induces ocular cancer cell death, a method for preventing or treating ocular cancer is also provided.

Method for treating ocular cancer

Compositions and methods for treating ocular cancer are provided. The composition is a subconjunctival formulation of nutlin-3 and its analogs. The composition provides for methods of treating ocular cancer, including retinoblastoma. The formulation has high penetration into ocular tissue with low toxicity.

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Memphis, TN, United States of America

Michael Dyer