A brain-penetrant CDK4/6 inhibitor - AU3-14 shows robust anti-tumor efficacy against glioblastoma.

The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in glioblastoma (GBM), the most aggressive and poorly prognosed brain malignancy. Despite extensive research, advances in GBM treatment have seen limited progress, with current therapy largely reliant on temozolomide (TMZ), underscoring the need for novel therapeutic strategies. This study explores the therapeutic potential of AU3-14, a potent and selective CDK4/6 inhibitor, for GBM.

A novel CDK4 inhibitor for myeloid protection in chemotherapy-treated triple-negative breast Cancer.

Background: Despite advances in cancer treatment, chemotherapy remains a cornerstone of clinical practice. However, its efficacy is often compromised by dose-limiting haematologic toxicities. Recent strategies aim to enhance chemotherapy tolerability while preserving its effectiveness.

Discovery of CDK5 Inhibitors through Structure-Guided Approach.

Specific abrogation of cyclin-dependent kinase 5 (CDK5) activity has been validated as a viable approach for the development of anticancer agents. However, no selective CDK5 inhibitor has been reported to date. Herein, a structure-based screening was employed to identify novel scaffolds from a library of compounds to identify potential CDK5 inhibitors that would be relevant for drug discovery.

Discovery of N-Phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine Derivatives as Potent Mnk2 Inhibitors: Design, Synthesis, SAR Analysis, and Evaluation of in vitro Anti-leukaemic Activity.

Background: Aberrant expression of eukaryotic translation initiation factor 4E (eIF4E) is common in many types of cancer including acute myeloid leukaemia (AML). Phosphorylation of eIF4E by MAPK-interacting kinases (Mnks) is essential for the eIF4E-mediated oncogenic activity. As such, the pharmacological inhibition of Mnks can be an effective strategy for the treatment of cancer.

A novel series of N-(pyridin-2-yl)-4-(thiazol-5-yl)pyrimidin-2-amines as highly potent CDK4/6 inhibitors.

Aim: 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.

Results: 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.

Highly Potent, Selective, and Orally Bioavailable 4-Thiazol-N-(pyridin-2-yl)pyrimidin-2-amine Cyclin-Dependent Kinases 4 and 6 Inhibitors as Anticancer Drug Candidates: Design, Synthesis, and Evaluation.

Cyclin D dependent kinases (CDK4 and CDK6) regulate entry into S phase of the cell cycle and are validated targets for anticancer drug discovery. Herein we detail the discovery of a novel series of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives as highly potent and selective inhibitors of CDK4 and CDK6. Medicinal chemistry optimization resulted in 83, an orally bioavailable inhibitor molecule with remarkable selectivity.

Targeting CDK9: a promising therapeutic opportunity in prostate cancer.

Cyclin-dependent kinase 9 (CDK9) is a key transcriptional regulator and a lucrative target for cancer treatment. Targeting CDK9 can effectively confine the hyperactivity of androgen receptor and the constitutive expression of anti-apoptotic proteins; both being main causes of prostate cancer (PCa) development and progression. In castrate-resistant PCa, traditional therapies that only target androgen receptor (AR) have become obsolete due to reprograming in AR activity to make the cells independent of androgen.

Knowledge, Attitude, and Utilization of Traditional Medicine among the Communities of Merawi Town, Northwest Ethiopia: A Cross-Sectional Study.

Background. In Ethiopia, up to 80% of the population use traditional medicine for primary health care. Studies on the current knowledge and practices of communities in the era of modern health care expansion are lacking.

In vivo antimalarial activity of the crude root and fruit extracts of Croton macrostachyus (Euphorbiaceae) against Plasmodium berghei in mice.

Euphorbiaceae (Croton macrostachyus H.; bā dòu) is used in Ethiopian folklore medicine for the treatment of malaria, gonorrhea, diabetes, wounds, fungal infections, and helminths. No scientific investigations have been performed to substantiate these claims.