Description
RO-3306 (872573-93-8) is a selective inhibitor of CDK1 (IC50?= 35 nM versus CDK2 IC50?= 340nM).1,2?It 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.3,4?It has also been demonstrated to overcome apoptotic resistance in BRAFV600E?human colorectal cancer cells.5
Uses
RO-3306 is an ATP-competitive and selective CDK1 inhibitor used against a diverse panel of human kinases. Used in the treatment of malignant tumors in conjunction with PARP inhibitors.
Uses
RO-3306 has been used:
- To study the significance of CA4-mediated cytotoxicity in mitotic arrest
- In cell cycle synchronization to conduct a study on proteomics
- As a CDK1 inhibitor, to prevent early mitotic entry
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) Vassilev?et al.?(2006),?Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1; Proc. Nat. Acad. Sci. USA?103?10660
2) Krasinska?et al.?(2008),?Selective chemical inhibition as a tool to study Cdk1 and Cdk2 functions in the cell cycle; Cell Cycle?7?1702
3) Pierce?et al.?(2013),?Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines; Cancer Biol. Ther.?14?537
4) Xia?et al.?(2014),?The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition;?Int. J. Oncol.?44?735
5) Zhang?et al.?(2018),?Targeting CDK1 and MEK/ERK Overcomes Apoptotic Resistance in BRAF-Mutant Human Colorectal Cancer; Mol. Cancer Res.?16?378
