Description
RO-3306 (872573-93-8) is a selective inhibitor of CDK1 (IC50= 35 nM versus CDK2 IC50= 340nM).1,2It induces G2/M phase cell cycle arrest and apoptosis. Inhibition of CDK1 with RO-3306 has been shown to have synergistic effects with PARP inhibitors in treating various breast cancers.3,4It has also been demonstrated to overcome apoptotic resistance in BRAFV600Ehuman colorectal cancer cells.5
Biochem/physiol Actions
RO-3306 is a selective ATP-competitive inhibitor of CDK1. It inhibites CDK1 cyclin B1 activity with Ki of 35 nM, nearly 10-fold selectivity relative to CDK2/cyclin E and over 50-fold relative to CDK4/cyclin D. RO-3306 has been used to cause cell cycle arrest at the G2/M boundary.
References
[1] LYUBOMIR T VASSILEV. Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2006: 10660-10665. DOI:
10.1073/pnas.0600447103[2] LILIANA KRASINSKA Daniel F Emilie Cot. Selective chemical inhibition as a tool to study Cdk1 and Cdk2 functions in the cell cycle.[J]. Cell Cycle, 2008: 1702-1708. DOI:
10.4161/cc.7.12.6101[3] AISLING PIERCE. Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines.[J]. Cancer Biology & Therapy, 2013, 14 6: 537-545. DOI:
10.4161/cbt.24349[4] QING XIA. The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition.[J]. International journal of oncology, 2014, 44 3: 735-744. DOI:
10.3892/ijo.2013.2240[5] PENG ZHANG. Targeting CDK1 and MEK/ERK Overcomes Apoptotic Resistance in BRAF-Mutant Human Colorectal Cancer.[J]. Molecular Cancer Research, 2018, 16 3: 378-389. DOI:
10.1158/1541-7786.mcr-17-0404
