characterisation of a tip60 specific inhibitor, nu9056, in prostate cancer描述一个特定抑制剂tip60 nu9056,前列腺癌.pdfVIP

Characterisation of a Tip60 Specific Inhibitor, NU9056, in Prostate Cancer 1 2,4 1 2,4 2,4 Kelly Coffey , Timothy J. Blackburn , Susan Cook , Bernard T. Golding , Roger J. Griffin , 2,4 1 3 1 2 Ian R. Hardcastle , Lorraine Hewitt , Kety Huberman , Hesta V. McNeill , David R. Newell , 2,4 1 2,4 1 Celine Roche , Claudia A. Ryan-Munden , Anna Watson , Craig N. Robson * 1 Solid Tumour Target Discovery Laboratory, Newcastle Cancer Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom, 2 Drug Discovery and Imaging Group, Newcastle Cancer Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom, 3 OSI Pharmaceuticals, Inc, Farmingdale, New York, United States of America, 4 Research and School of Chemistry, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom Abstract Tip60 (KAT5) is a histone acetyltransferase (HAT enzyme) involved in multiple cellular processes including transcriptional regulation, DNA damage repair and cell signalling. In prostate cancer, aggressive cases over-express Tip60 which functions as an androgen receptor co-activator via direct acetylation of lysine residues within the KLKK motif of the receptor hinge region. The purpose of this study was to identify and characterise a Tip60 acetylase inhibitor. High-throughput screening revealed an isothiazole that inhibite