Molecular docking and dynamics based approach for the identification of kinase inhibitors targeting PI3Kα against non-small cell lung cancer: a computational study

RSC Advances, Год журнала: 2022, Номер 12(33), С. 21452 - 21467

Опубликована: Янв. 1, 2022

Non-small cell lung cancer (NSCLC) is an obscure disease whose incidence increasing worldwide day by day, and PI3Kα one of the major targets for proliferation due to mutation. Since PI3K a class kinase enzyme, no in silico research has been performed on inhibition mutation small molecules, we have selected protein inhibitor database energy minimization process ligand preparation. The key objective this identify potential hits from library further perform lead optimization molecular docking dynamics approach. And so, was (PDB ID: 4JPS), having unique specific binding pocket with amino acid residue activity. After protocol validation, structure-based virtual screening MMGBSA affinity calculations were total ten reported. Detailed analysis best scoring molecules ADMET analysis, induced fit (IFD) (MD) simulation. Two - 6943 34100 considered showed better results than Copanlisib assessment, Furthermore, synthetic accessibility two compounds investigated using SwissADME, are easier synthesize Copanlisib. Computational drug discovery tools used identification inhibitors as anti-cancer agents NSCLC present research.

Язык: Английский

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Enhanced Chemoprevention of Prostate Cancer by Combining Arctigenin with Green Tea and Quercetin in Prostate-Specific Phosphatase and Tensin Homolog Knockout Mice

Biomolecules, Год журнала: 2024, Номер 14(1), С. 105 - 105

Опубликована: Янв. 14, 2024

The low bioavailability of most phytochemicals limits their anticancer effects in humans. present study was designed to test whether combining arctigenin (Arc), a lignan mainly from the seed Arctium lappa, with green tea (GT) and quercetin (Q) enhances chemopreventive effect on prostate cancer. We performed vitro proliferation studies different cell lines. observed strong synergistic anti-proliferative GT+Q+Arc exposing androgen-sensitive human cancer LNCaP cells. pre-malignant WPE1-NA22 line more sensitive this combination. No cytotoxicity normal epithelial PrEC For an vivo study, 3-week-old, prostate-specific PTEN (phosphatase tensin homolog) knockout mice were treated GT+Q, Arc, GT+Q+Arc, or control daily until 16 weeks age. In imaging using membrane antigen (PSMA) probes demonstrated that tumorigenesis significantly inhibited by 40% (GT+Q), 60% (Arc at 30 mg/kg bw), 90% (GT+Q+Arc) compared control. A pathological examination showed all developed invasive adenocarcinoma. contrast, primary lesion GT+Q Arc alone groups high-grade prostatic intraepithelial neoplasia (PIN), low-grade PIN group. combined associated increased inhibition androgen receptor, PI3K/Akt pathway, Ki67 expression, angiogenesis. This demonstrates GT Q highly effective chemoprevention. These results warrant clinical trials confirm efficacy combination

Язык: Английский

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Emerging biomarkers and molecular targets for precision medicine in cervical cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(3), С. 189106 - 189106

Опубликована: Май 1, 2024

Язык: Английский

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Ferroptosis and circular RNAs: new horizons in cancer therapy.

PubMed, Год журнала: 2024, Номер 23, С. 570 - 599

Опубликована: Янв. 1, 2024

Cancer poses intricate challenges to treatment due its complexity and diversity. Ferroptosis circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators pivotal influencers ferroptosis in cell lines. The results underscore significance modulating pathways that impact crucial aspects development, including survival, proliferation, metastasis. A detailed analysis delineates these pathways, shedding light on mechanisms through which influence ferroptosis. Building upon recent experimental findings, study evaluates potential targeting induce By identifying specific associated with etiology cancer, this paves way for development targeted therapeutics exploit vulnerabilities cells. This review consolidates existing understanding circRNAs, emphasizing role therapy providing impetus ongoing research dynamic field. See also graphical abstract(Fig. 1).

Язык: Английский

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer: Current Use and Future Prospects

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 10008 - 10008

Опубликована: Сен. 17, 2024

Tyrosine kinase inhibitors (TKIs) have emerged as a leading targeted cancer therapy, reducing the side effects often seen with non-targeted treatments, especially damage to healthy cells. To tackle resistance, typically caused by epidermal growth factor receptor (EGFR) mutations, four generations of TKIs been developed. Each generation has shown improved effectiveness and fewer effects, resulting in better patient outcomes. For example, patients on gefitinib, first-generation TKI, experienced progression-free survival (PFS) 10 months compared 5 conventional chemotherapy. Second-generation TKI afatinib outperformed erlotinib extended PFS 11.1 6.9 cisplatin. Third-generation further increased 38.6 months, 31.8 TKIs. This progress demonstrates ability newer overcome particularly T790M mutation, while adverse effects. Ongoing research focuses overcoming resistance from mutations like C797S improve survival. These developments highlight significant therapy continued effort refine treatment. Recent South Korea shows that third-generation are ineffective against non-small cell lung (NSCLC) mutation. Several trials started showing promising vitro vivo results, but more needed before clinical approval. review underscores notable advancements field EGFR TKIs, offering comprehensive analysis their mechanisms action progression various response resistance.

Язык: Английский

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