Using a high-throughput screening campaign, we identified the 4,6-bis anilino pyrimidines as inhibitors of the cyclin-dependent kinase, CDK4. Herein we describe the further chemical modification and use of X-ray crystallography to develop potent and selective in vitro inhibitors of CDK4.
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http://dx.doi.org/10.1016/s0960-894x(03)00202-6 | DOI Listing |
Cell Biochem Biophys
December 2024
Biology Department, Université de Moncton, Moncton, NB, Canada.
Targeting more than one in nine men before age 70, prostate cancer is the most common type of cancer in men. The increased levels of cyclins, leading to activation of cyclin-dependent kinases (CDKs), play a critical role in the increased proliferation of prostate cancer cells. In this study, the regulation of the cyclin D1 (CCND1) promoter activity by activator protein-1 (AP-1) and SRY-related HMG-box (SOX) transcription factors has been characterized in PC3 prostate cancer cells.
View Article and Find Full Text PDFCurr Oncol
November 2024
Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, Turkey.
Background/objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort.
Methods: This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey.
Biogerontology
December 2024
Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Chronic kidney diseases (CKD) are a group of multi-factorial disorders that markedly impair kidney functions with progressive renal deterioration. Aging contributes to age-specific phenotypes in kidneys, which undergo several structural and functional alterations, such as a decline in regenerative capacity and increased fibrosis, inflammation, and tubular atrophy, all predisposing them to disease and increasing their susceptibility to injury while impeding their recovery. A central feature of these age-related processes is the activation of the p53/p21 pathway signaling.
View Article and Find Full Text PDFCell Biol Toxicol
December 2024
Department of General Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China.
The prevalence of breast cancer (BRCA) is notable in the female population, being a commonly diagnosed malignancy, where the management of copper levels is crucial for treatment success. This research aims to explore the influence of copper homeostasis on BRCA therapy, with a specific focus on the role of Cyclin-Dependent Kinase 1 (CDK1) and its relationship to copper regulation. A novel thermosensitive hydrogel incorporating nanoparticles (NPs) was engineered to synergize with the chemotherapy drug vincristine (VCR) in inhibiting tumor growth and metastasis.
View Article and Find Full Text PDFChem Pharm Bull (Tokyo)
December 2024
Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
Osteoporosis is treated with oral and parenteral resorption inhibitors and parenteral osteogenic drugs. However, orally active small-molecule osteogenic drugs are not clinically available. Natural coumarin derivatives, such as osthole, exert osteoblastogenic effects.
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