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Type: Journal article
Title: A novel series of N-(pyridin-2-yl)-4-(thiazol-5-yl)pyrimidin-2-amines as highly potent CDK4/6 inhibitors
Author: Tadesse, S.
Zhu, G.
Mekonnen, L.
Lenjisa, J.
Yu, M.
Brown, M.
Wang, S.
Citation: Future Medicinal Chemistry, 2017; 9(13):1495-1506
Publisher: Future Science
Issue Date: 2017
ISSN: 1756-8919
Statement of
Solomon Tadesse, Ge Zhu, Laychiluh B Mekonnen, Jimma L Lenjisa, Mingfeng Yu, Michael P Brown, Shudong Wang
Abstract: Inhibitors of CDK4/6 have emerged as a powerful class of therapeutics for treatment of several malignancies. We herein describe the identification of a new series of molecules that demonstrated excellent selectivity for CDK4/6 over CDKs1, 7 and 9.Medicinal chemistry optimization led to the discovery of 58 and 69 that inhibited CDK4 and CDK4/6, respectively, with high potency and selectivity, and 58 and 69 exhibited potent antiproliferative activities in a panel of human cancer cell lines including leukemia, and cancers of the breast, colon, ovary, pancreas and prostate.Compounds 58 and 69 caused remarkable growth inhibition of melanoma cells, particularly the cells harboring multiple BRAF and NRAS mutations, via a CDK4/6-targeted mechanism of action. [Formula: see text].
Keywords: Cell Line, Tumor
GTP Phosphohydrolases
Proto-Oncogene Proteins B-raf
Retinoblastoma Protein
Membrane Proteins
Protein Kinase Inhibitors
Cell Proliferation
Binding Sites
Protein Structure, Tertiary
Protein Binding
Structure-Activity Relationship
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
G1 Phase Cell Cycle Checkpoints
Rights: © 2017 Future Science Ltd.
DOI: 10.4155/fmc-2017-0076
Appears in Collections:Aurora harvest 4
Biochemistry publications

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