Pretreatment with diltiazem and nicardipine increased lapatinib exposure, whereas pretreatment with verapamil reduced it. These findings from preclinical models suggest the potential for drug-drug interactions between lapatinib and calcium channel blockers, warranting further clinical investigation.

No obvious toxic reaction was observed. By activating STING/TBK1/IRF3 signaling, TET enhanced CD8+ T cell-mediated anti-tumor immunity, thereby markedly enhancing anti-PD-1 therapy efficacy in HCC.

P2, N=309, Active, not recruiting, Global Alliance for TB Drug Development | Trial completion date: Jun 2026 --> Feb 2027

By utilising gene-edited HIOs derived from the same donor, we reveal epithelial cell-intrinsic mechanisms downstream of CFTR loss. These findings, enabled by our experimental approach, offer important insights into the role of the intestinal epithelium in CF, independent of immune cells, the microbiome, and inflammation. They also lend support for therapeutic targeting of calcium signalling to reverse disease-associated transcriptomic changes.

In addition, five prediction software tools were used to estimate pharmacokinetic parameters relevant to the BBB penetration of the two compounds. Finally, the method was applied in preclinical pharmacokinetic studies using elacridar, an efflux transporter inhibitor.

P4, N=100, Recruiting, Weill Medical College of Cornell University | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

This study emphasizes the significant association of ABCB1 genotype (TT at rs1045642) with vincristine-associated neuropathy and highlights the relevance of higher average doses of vincristine in causing neurotoxicity.

TET and TMZ significantly reduced pro-MMP-2 levels in M010b cells under both conditions and in U87 cells under normoxia. In conclusion, given the limited therapeutic potential of TMZ, our findings suggest that TET could be a viable alternative treatment option for GBM.

Compound 17 exhibited the strongest cytotoxic effect against HepG2 cells with an IC50 value of 2.09 μM and a satisfactory SI value of 11.5, which was 5.3- and 6.4-fold higher than the activity of parental tetrandrine and adriamycin, respectively. Moreover, it indicates a potent in vivo killing effect against liver cancers, orthotopically transplanted HCC in an AKT1-dependent manner, with a safety profile. Taken together, compound 17 shows therapeutic potential as a safe anticancer agent through apoptosis induction, worthy of further development.

Compound 3 (3α-dihydrocadambine) effectively revealed strong vasodilatory activity with EC50 values of 2.4 μM and 2.1 μM, respectively, similar levels comparable to the positive control (verapamil)...Moreover, network pharmacology and molecular docking predicted compound 1 to correlate with the p53-Hippo-TGF-β antitumor signalling pathway and compound 3 with the cAMP/cGMP-PKG cardiovascular signalling pathway. This work provides preliminary experimental data for the development of potential lead compounds from U. gambir.

Bulk and single-cell transcriptomic analyses further revealed complement-associated activation, extracellular-matrix remodeling, and enrichment of antigen-presenting and inflammatory macrophage programs. Thus, TETNPs@Gel functions as an in situ nanovaccine rather than a conventional cytotoxic formulation, in which controlled tetrandrine release couples direct tumor-cell killing with vascular and immune re-education, offering a potentially generalizable platform for localized immunochemotherapy in solid tumors.

Abcb1a/1b-mediated transport of daraxonrasib across the BBB was validated by oral co-administration of the ABCB1/ABCG2 inhibitor elacridar, resulting in 20-fold increased brain penetration in wild-type mice (P < 0.01). ABCB1 function could limit brain penetration and possibly efficacy of daraxonrasib against brain metastases. Collectively, these preclinical findings may help in optimizing the application of daraxonrasib in clinical settings.