Johns Hopkins University

Venu Raman

Ramachandra S Hosmane

Guus Martinus Bol

Paul Joannes Van Diest

Phuoc Tran

Raj Kumar

The invention encompasses methods for treating or preventing diseases and disorders associated abnormal cell growth, for example, treating or preventing cancer or tumor growth, by administering to a subject in need thereof a composition comprising a therapeutically or prophylactically effective amount of a compound that downregulates DDX3, for example a fused diimidazodiazepine ring compound or a pharmaceutically acceptable salt thereof. The invention also encompasses the use of DDX3 as a biomarker for diagnostic and treatment purposes, for example, to identify a hyperproliferative disorder susceptible to treatment by down regulation of DDX3.

DDX3 as a biomarker for cancer and methods related thereto

Provided herein is the compound RK-33, or a salt, solvate, stereoisomer, or derivative thereof, which is shown to be an inhibitor if the DEAD box helicase DDX3, in mammalian cells. RK-33 is also provided herein for use as a radiation dose sensitizer in a subject suffering from a proliferative disease and undergoing radiation therapy. Methods of treatment of proliferative diseases, such as cancer with a combination of RK-33 and radiotherapy methods such as stereotactic ablative radiotherapy (SABR) are also provided.

Compounds and methods of use in ablative radiotherapy

The invention encompasses novel compounds and pharmaceutically acceptable salts thereof and compositions including therapeutically or prophylactically effective amounts of such compounds or pharmaceutically acceptable salts thereof. The invention also encompasses methods for treating or preventing diseases and disorders associated abnormal cell growth, for example, treating or preventing cancer or tumor growth, which methods include administering to a mammal in need thereof a composition comprising a therapeutically or prophylactically effective amount of a compound of the invention or a pharmaceutically acceptable salt thereof.

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Ellicott City, MD, United States of America

Venu Raman