Sorafenib, Salubrinal, and Roscovitine were positively correlated with the risk score, whereas WO2009093972 was negatively correlated. Additionally, this study identified several target genes such as FBXO25 with TINAG, CCDC28A with EPHB2, and SH2D6 with FCN3, with subsequent validation achieved through qPCR and western blotting. In conclusion, this study identifies three prognostic genes, providing new insights into CRC pathogenesis and potential therapeutic strategies.

P2, N=124, Recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Jan 2026 --> Jan 2027

Among the tested compounds, 7-(4-bromophenyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidine-3‑carbonitrile (13 g), 7-(2,4-dichlorophenyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidine-3‑carbonitrile (13j), 7-[1-(4-fluorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl)-2-(methylthio)pyrazolo[1,5-a] pyrimidine-3‑carbonitrile (21c), and 7-(6-bromo-2-oxo-2H-chromen-3-yl)-2-(methylthio)pyrazolo[1,5-a] pyrimidine-3‑carbonitrile (26b) exhibited strong growth inhibition in HCT-116 cells, comparable to the reference drug roscovitine...Molecular docking studies supported these results, showing favorable interactions of compound 21c within the CDK2 active site. Overall, compound 21c emerges as a promising lead candidate for the development of selective CDK2 inhibitors exhibiting potent anti-cancer activity and low toxicity toward normal cells.

THBS3-high breast cancer patients exhibited resistance to Dinaciclib, Daporinad, and Rapamycin. THBS3 may promote breast cancer progression through immune regulation, ECM remodeling, and drug resistance mechanisms, suggesting its potential as a therapeutic target. These findings support enhanced breast cancer screening in IBD patients.

AS601245, AP.24534 and roscovitine were the top three chemotherapeutic agents showing the highest sensitivity differences between the risk groups. The RT-qPCR results indicated that the expression of electron transfer flavoprotein subunit α, rap guanine nucleotide exchange factor-like 1, keratin 7, cluster of differentiation 24, proline rich 15-like, arachidonate 15-lipoxygenase type B, ELOVL fatty acid elongase 2 and C-X-C motif chemokine ligand 9 was consistent with the results of bioinformatic analysis. In conclusion, the HER2-related risk model and nomogram developed in the present study demonstrated high accuracy in predicting patient survival.

However, they displayed a dose-dependent inhibition of CDK2 kinase activity in in-vitro ADP-Glo™ assay with IC50 values of 23.47 and 82.04 nM, respectively, compared to 0.51 and 700 nM for Dinaciclib and Roscovitine, respectively. Compound 6 downregulated CDK2 protein targets involved in DNA replication process; Polα, MCM7, ORC2, and ORC4 in CRC cell lines. Subjected to cell cycle analysis, HCT-116 and HT-29 treated with compound 6 demonstrated pre-G1 phase arrest with no similar observation in S phase.

A HB patient-derived xenograft (PDX) model was treated with placebo, vincristine + irinotecan (VI), dinaciclib, or VI + dinaciclib to evaluate tumor growth and response to therapy. In our PDX model, treatment with VI + dinaciclib resulted in decreased tumor volume, viability and HB cell proliferation. Given these findings, combination treatment with VI and dinaciclib should be investigated further as a treatment for chemoresistant HB.

Compounds 4, 7, and 10 revealed significant CDK2 inhibitory activities with comparable potencies (IC50 = 0.75, 0.77 and 0.85 µM, respectively) to that of roscovitine (IC50 = 0.99 µM)...Further investigation on the mechanism demonstrated that 5 induced apoptosis, increased the proapoptotic protein Bax level, and reduced the antiapoptotic Bcl-2 level in the cells of MCF-7. Finally, the molecular docking study showed bioactive analogues that fit well in the CDK2 active site via various interactions.

The 4 MRGs may contribute to the understanding on UPRmt in LUAD and the development of relevant medicine in clinical practice.

Drug sensitivity analysis identified four promising therapeutic compounds-PD-0325901, Bryostatin-1, ATRA, and Roscovitine-with potential clinical utility for ESCC treatment. The findings of this study offer clinically relevant insights for prognostic stratification and characterization of the immune microenvironment in ESCC patients. Moreover, these results provide novel perspectives that may contribute to the development of more effective prognostic tools and targeted therapeutic strategies for ESCC management.

The hexokinase activity of HKDC1 is also insensitive to Dinaciclib, a pan cyclin-dependent kinase inhibitor that reportedly disrupts the ability of nuclear localized HKDC1 to phosphorylate retinoblastoma-binding protein 5...An HKDC1 variant associated with retinitis pigmentosa, T58M, displays a modest, but statistically significant 2-fold decrease in catalytic efficiency (kcat/Km,glucose) compared to the wild-type enzyme. Together, our results provide a detailed functional characterization of recombinant HKDC1 and set the stage for investigating the link between HKDC1 catalysis and human disease.

Additionally, extended 200 ns molecular dynamics simulations further validated the complexes, revealing stable RMSD, reduced SASA, favorable hydrogen bonding, and strong MM-GBSA binding free energies (△G_bind = -42.6 kcal·mol-1 for sarcorine C vs -40.8 kcal·mol-1 for roscovitine). These findings establish S. saligna as a promising source of anticancer steroidal alkaloids and report, for the first time, the selective cytotoxic activity of sarcorine C and salonine C against colon cancer cells, supported by integrated experimental and computational evidence.