These findings support the further development of multi-target CDK inhibitors as promising candidates to overcome tumor progression and therapeutic resistance in lung cancer.

Moreover, the half-maximum inhibitory concentration (IC50) values for 85 drugs, such as roscovitine and embelin, were markedly distinct between the two risk groups...RT-qPCR results confirmed that TNF, PTPN6, FASN, and TFRC were upregulated in CESC, consistent with the Wilcoxon test findings. This study established an MCD-associated prognostic model for CESC, highlighting its link to the TME and its potential to enhance prognostic predictions.

This ADP-ribosylation-based prognostic model reliably predicts LUAD survival and identifies potential biomarkers for tailored therapy.

IBSP represents an independent prognostic biomarker associated with adverse outcomes in glioma. These findings provide insight into the molecular mechanisms underlying IBSP-associated glioma progression and highlight potential therapeutic targets that may contribute to improved clinical outcomes in patients with glioma.

Leads 12c, 12i, and 22 demonstrated potent kinase inhibition, with 22 yielding a CDK-2 IC₅₀ of 0.03 µM (seliciclib: 0.02 µM), and 12c delivering an EGFR IC₅₀ of 0.12 µM (erlotinib: 0.01 µM). Promising ADMET profiles and good drug likeness are evident in these leads. These data underscore the great potential of this scaffold for developing dual EGF/CDK-2 inhibitors aimed at resistance mechanisms in more aggressive cancers and can thus be pursued further in preclinical optimization.

In vitro experiments demonstrated that overexpression of NOTCH2NLA in breast cancer cells promoted cell growth and enhanced sensitivity to AT-7519 treatment. Collectively, our findings suggest that NOTCH2NLA amplification may be a new prognostic marker of BRCA and cell cycle inhibitors were more suitable for therapy on BRCA patients with NOTCH2NLA amplification.

Among the tested analogs, 6e, 6f, and 6 g exerted promising cytotoxicity toward HS 578 T cells where compound 6f exhibited significant antiproliferative activity with an IC50 of 3.06 µM, exceeding that of Lapatinib by 7.6 fold...The findings illustrated that analog 6f exerted the most potent CDK-2 inhibition with an IC50 equal to 0.277 µM, which is approximately threefold the activity of Roscovitine (0.833 µM). As well, compound 6f arrested HS 578 T cell cycle at both S and G2/M phases and stimulated apoptosis by increasing Bax and Caspase-3 expression with a concurrent decline in the expression of Bcl-2. Additionally, ADMET prediction and the binding interaction of the most active derivatives with CDK-2 have been studied in silico to evaluate their potential as important antitumor agents.

We establish NNMT as a central metabolic-immune hub that orchestrates TGF-β-mediated CD8⁺ T cell dysfunction and endothelial reprogramming in ccRCC.

To our knowledge, this is the first demonstration of a SL interaction that exploits a heterozygous disease state in HGSC. These findings highlight CDK2 inhibition as a promising precision medicine strategy for RBX1-deficient tumors, broaden the applicability of SL approaches beyond homozygous gene loss, and provide strong preclinical rationale for further therapeutic development.

P2, N=72, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

Exploratory drug-response modeling with pRRophetic suggested lower estimated half-maximal inhibitory concentration (IC50) values for agents including MS-275 (entinostat), PF-4708671, and roscovitine in the high-risk group. The TIDE algorithm carries prognostic information in NSCLC beyond immunotherapy settings. The proposed TIDE-informed gene signature reproduced prognostic stratification across cohorts, suggesting potential applicability to a broader NSCLC population and supporting future personalized risk stratification.

P1, N=40, Completed, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Unknown status --> Completed | N=30 --> 40