Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Cancer

Cancer

BET bromodomain proteins; smoothened (SMO)

Mouse and cell culture studies suggest BET bromodomain inhibitors could be useful for treating drug-resistant, hedgehog pathway-driven cancers. In hedgehog pathway-driven mouse medulloblastoma cell lines, the BET bromodomain antagonist JQ1 inhibited proliferation with IC50 values of 50 to 150 nM. In multiple mouse allograft models of hedgehog pathway-driven cancers that are resistant to SMO inhibitors, JQ1 decreased tumor growth compared with vehicle. Next steps include testing therapeutic combinations for BET inhibitors in SMO inhibitor-resistant cancers.

At least five companies have BET bromodomain inhibitors in Phase I testing or preclinical development for various cancers.
Tensha Therapeutics Inc. has the JQ1-derived small molecule BET bromodomain inhibitor TEN-010 in Phase I testing to treat solid tumors.

At least four other companies have BET bromodomain inhibitors in Phase I testing or preclinical development for various cancers.

SciBX 7(28); doi:10.1038/scibx.2014.822
Published online July 24, 2014

Patent application covering JQ1 and related analogs filed by Dana-Farber Cancer Institute; licensed to Tensha Therapeutics

Tang, Y. et al. Nat. Med.; published online June 29, 2014;
doi:10.1038/nm.3613
Contact: Yoon-Jae Cho, Stanford University School of Medicine, Stanford, Calif.
e-mail:

yjcho1@stanford.edu