دورية
Free–WilsonAnalysis of Comprehensive Dataon Phosphoinositide-3-kinase (PI3K) Inhibitors Reveals Importanceof N-Methylation for PI3Kd Activity
| العنوان: | Free–WilsonAnalysis of Comprehensive Dataon Phosphoinositide-3-kinase (PI3K) Inhibitors Reveals Importanceof N-Methylation for PI3Kd Activity |
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| المؤلفون: | Barnes, Lydia, Blaber, Hollie, Brooks, David T. K., Byers, Lewis, Buckley, Daniel, Byron, Zoe C., Chilvers, Richard G., Cochrane, Liam, Cooney, Edward, Damian, Heather A., Francis, Luke, Fu He, Daniel, Grace, Jack M. J., Green, Harley J., Hogarth, Edmund J. P., Jusu, Leyla, Killalea, C. Elizabeth, King, Oliver, Lambert, Joseph, Lee, Zoe J., Lima, Nuria S., Long, Christina L., Mackinnon, May-Li, Mahdy, Shusha, Matthews-Wright, Jolyon, Millward, Makenzie J., Meehan, Matthew F., Merrett, Christopher, Morrison, Lisa, Parke, Hal R. I., Payne, Charlotte, Payne, Lawrence, Pike, Craig, Seal, Alexander, Senior, Aaron J., Smith, Keenan M., Stanelyte, Kamile, Stillibrand, Joe, Szpara, Rachel, Taday, Freya F. H., Threadgould, Antony M., Trainor, Rohan J., Waters, Jordan, Williams, Oliver, Wong, Carrie K. W., Wood, Katherine, Barton, Nick, Gruszka, Anna, Henley, Zoe, Rowedder, James E., Cookson, Rosa, Jones, Katherine L., Nadin, Alan, Smith, Ian E., Macdonald, Simon J. F., Nortcliffe, Andrew |
| المصدر: | Journal of Medicinal Chemistry; January 2019, Vol. 62 Issue: 1 |
| مستخلص: | Phosphoinositide-3-kinase d (PI3Kd) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3Kd over the closely related isoforms. Interrogation through the Free–Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3Kd and provides a predictive model for the activity against the PI3K isoforms. |
| قاعدة البيانات: | Supplemental Index |
Find this issue from the American Chemical Society | تدمد: | 00222623 15204804 |
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| DOI: | 10.1021/acs.jmedchem.9b01499 |