Vertex Pharmaceuticals, Inc.

Wanjung Tsai

William Markland

David A Newsome

Marina S Penney

Diane M Boucher

Brian J Hare

Shawn M Hillier

Mark Willem Ledeboer

Ales Medek

Valdas Jurkauskas

Yi Shi

Michael Waldo

Praveen Mudunuri

Randal Byrn

Kwame Wiredu Nti-Addae

Steven Jones

Sarah Robertson

Mohammed Asmal

Simon Adam O'Neil

John Gregg Van Alsten

Dainius Macikenas

Sarah Marie Robertson

Described herein are methods of treating a proliferative disease in a subject by administering a DNA-damaging agent and between about 8 and about 48 hours later administering to the subject a DNA-PK inhibitor. Exemplary DNA-PK inhibitors are represented by Formula (B-I): and by pharmaceutically acceptable salts thereof, wherein R, Q, Ring A, and Ring B are as defined herein.

Method for treating cancer using a combination of DNA-damaging agents and DNA-PK inhibitors

Described herein are methods of treating a proliferative disease in a subject by administering a DNA-damaging agent and between about 8 and about 48 hours later administering to the subject a DNA-PK inhibitor. Exemplary DNA-PK inhibitors are represented by Formula (B-I): and by pharmaceutically acceptable salts thereof, wherein R, Q, Ring A, and Ring B are as defined herein. 

Polymorphic forms of Compound (1) or a pharmaceutically acceptable salt thereof, wherein Compound (1) is represented by the following structural formula: are Form A of HCl salt of Compound (1).&#xbd;HO, Form F of HCl salt of Compound (1).3HO, Form D of HCl salt of Compound (1), Form A of Compound (1), and Form A of tosylate salt of Compound (1). Such polymorphic forms are employed for treating influenza, inhibiting the replication of influenza viruses, or reducing the amount of influenza viruses in a biological sample or in a subject.

Inhibitors of influenza viruses replication

Growing community of inventors

Boston, MA, United States of America

Wanjung Tsai