The stress-responsive kinase DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress.

To survive proteotoxic stress, cancer cells activate the proteotoxic-stress response pathway, which is controlled by the transcription factor heat shock factor 1 (HSF1). This pathway supports cancer initiation, cancer progression and chemoresistance and thus is an attractive therapeutic target. As developing inhibitors against transcriptional regulators, such as HSF1 is challenging, the identification and targeting of upstream regulators of HSF1 present a tractable alternative strategy.

The role of neutral Rh(PONOP)H, free NMeH, boronium and ammonium salts in the dehydrocoupling of dimethylamine-borane using the cationic pincer [Rh(PONOP)(η-H)] catalyst.

The σ-amine-borane pincer complex [Rh(PONOP)(η1-H3B·NMe3)][BArF4] [2, PONOP = κ3-NC5H3-2,6-(OPtBu2)2] is prepared by addition of H3B·NMe3 to the dihydrogen precursor [Rh(PONOP)(η2-H2)][BArF4], 1. In a similar way the related H3B·NMe2H complex [Rh(PONOP)(η1-H3B·NMe2H)][BArF4], 3, can be made in situ, but this undergoes dehydrocoupling to reform 1 and give the aminoborane dimer [H2BNMe2]2. NMR studies on this system reveal an intermediate neutral hydride forms, Rh(PONOP)H, 4, that has been prepared independently.