City of Hope

California Institute of Technology

Binghui Shen

Li Zheng

Jun Xie

David A Horne

Judith L Campbell

Hongzhi Li

Kenneth Karanja

Ravi Salgia

Karen Reckamp

Disclosed herein, inter alia, are compositions and methods for inhibiting DNA2.

DNA2 inhibitors for cancer treatment

Provided herein, inter alia, are methods, compositions and kits for treating cancer in a subject. The methods include administration of one or more tyrosine kinase inhibitors and triptolide or an analog thereof to the subject. The methods, compositions and kits are effective for preventing resistance and/or increasing sensitivity to tyrosine kinase inhibitors.

Methods and compositions comprising tyrosine kinase inhibitor and triptolide for the treatment of cancer

FEN-1 is involved in processing HIV central DNA flap (CDF) and is a target for intervention of HIV-1 replication. Inhibition of HIV-1 CDF removal by expression of D181A FEN-1 mutant suppresses viral DNA replication, further demonstrating that FEN-1 is a target. Methods of identifying and using molecules that inhibit FEN-1 processing HIV-1 CDF and other methods of inhibiting FEN-1 processing are provided. Useful small molecules specifically suppress FEN-1 cleavage of HIV CDF but have little effect on FEN-1's function in RNA-DNA primer removal. Pentamidine inhibits HIV replication by suppressing FEN-1-mediated HIV-CDF processing.

Suppression of HIV-1 replication via inhibition of human flap endonuclease-1-mediated HIV-1 central DNA flap processing

Growing community of inventors

La Verne, CA, United States of America

Binghui Shen