Robert N Booher, Harold Hatch, Brian M Dolinski, Thi Nguyen, Lauren Harmonay, Ali-Samer Al-Assaad, Mark Ayers, Michael Nebozhyn, Andrey Loboda, Heather A Hirsch, Theresa Zhang, Bin Shi, Carrie E Merkel, Minilik H Angagaw, Yaolin Wang, Brian J Long, Xianlu Q Lennon, Nathan Miselis, Vincenzo Pucci, James W Monahan, Junghoon Lee, Anna Georgieva Kondic, Eun Kyung Im, David Mauro, Rebecca Blanchard, Gary Gilliland, Stephen E Fawell, Leigh Zawel, Alwin G Schuller, Peter Strack
Dinaciclib is a potent CDK1, 2, 5 and 9 inhibitor being developed for the treatment of cancer. Additional understanding of antitumor mechanisms and identification of predictive biomarkers are important for its clinical development. Here we demonstrate that while dinaciclib can effectively block cell cycle progression, in vitro and in vivo studies, coupled with mouse and human pharmacokinetics, support a model whereby induction of apoptosis is a main mechanism of dinaciclib's antitumor effect and relevant to the clinical duration of exposure...
2014: PloS One