ORCID Profile
0000-0003-3600-0400
Current Organisations
Addis Ababa University
,
Jimma University
,
Mekelle University
,
University of Tasmania
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Publisher: Springer International Publishing
Date: 2021
Publisher: Edith Cowan University
Date: 2013
Publisher: Informa UK Limited
Date: 10-07-2018
Publisher: Informa UK Limited
Date: 28-02-2018
Publisher: Informa UK Limited
Date: 28-10-2023
Publisher: Informa UK Limited
Date: 04-2013
Publisher: Informa UK Limited
Date: 20-06-2020
Publisher: Informa UK Limited
Date: 05-05-2017
Publisher: MDPI AG
Date: 25-03-2023
DOI: 10.3390/MOLECULES28072951
Abstract: Cyclin-dependent kinase 2 (CDK2) has been garnering considerable interest as a target to develop new cancer treatments and to ameliorate resistance to CDK4/6 inhibitors. However, a selective CDK2 inhibitor has yet to be clinically approved. With the desire to discover novel, potent, and selective CDK2 inhibitors, the phenylsulfonamide moiety of our previous lead compound 1 was bioisosterically replaced with pyrazole derivatives, affording a novel series of N,4-di(1H-pyrazol-4-yl)pyrimidin-2-amines that exhibited potent CDK2 inhibitory activity. Among them, 15 was the most potent CDK2 inhibitor (Ki = 0.005 µM) with a degree of selectivity over other CDKs tested. Meanwhile, this compound displayed sub-micromolar antiproliferative activity against a panel of 13 cancer cell lines (GI50 = 0.127–0.560 μM). Mechanistic studies in ovarian cancer cells revealed that 15 reduced the phosphorylation of retinoblastoma at Thr821, arrested cells at the S and G2/M phases, and induced apoptosis. These results accentuate the potential of the N,4-di(1H-pyrazol-4-yl)pyrimidin-2-amine scaffold to be developed into potent and selective CDK2 inhibitors for the treatment of cancer.
Publisher: Informa UK Limited
Date: 27-02-2018
Publisher: Edith Cowan University
Date: 30-04-2018
Publisher: Edith Cowan University
Date: 05-2019
No related grants have been discovered for Jillian Downing.