Discovery of Potent Quinone Oxidoreductase 2 inhibitors to Overcome TRAIL Resistance of non-small cell lung cancer

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 288, P. 117382 - 117382

Published: Feb. 16, 2025

Language: Английский

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Targeting estrogen metabolism in high-grade serous ovarian cancer shows promise to overcome platinum resistance

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117069 - 117069

Published: July 4, 2024

The high mortality rate due to chemoresistance in patients with high-grade ovarian cancer (HGSOC) emphasizes the urgent need determine optimal treatment strategies for advanced and recurrent cases. Our study investigates interplay between estrogens HGSOC shows clear differences platinum-sensitive -resistant tumors. Through comprehensive transcriptome analyzes, we uncover expression of genes estrogen biosynthesis, metabolism, transport action underlying platinum resistance different tissues subtypes six cell lines. Furthermore, identify involved biosynthesis metabolism as prognostic biomarkers HGSOC. Additionally, our elucidates patterns formation/metabolism their effects on proliferation lines sensitivity. These results emphasize dynamic chemoresistance. In particular, targeting activity steroid sulfatase (STS) proves be a promising therapeutic approach potential efficacy limiting estrogen-driven proliferation. reveals markers well identifies novel targets that show promise overcoming improving outcomes

Language: Английский

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1,2,4-Triazolo[4,3-b]pyridazine analogues: synthesis, evaluation of cytotoxicity, anticancer activity and computational analysis

Journal of the Iranian Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Language: Английский

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Melatonin Receptor Expression in Primary Uveal Melanoma

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8711 - 8711

Published: Aug. 9, 2024

Melatonin, noted for its anti-cancer properties in various malignancies, including cutaneous melanoma, shows promise Uveal melanoma (UM) treatment. This study aimed to evaluate melatonin receptor expression primary UM and association with UM-related mortality prognostic factors. Immunohistochemical analysis of 47 tissues showed low 1A (MTNR1A) 1B (MTNR1B), MTNR1A significantly higher patients who succumbed UM. Analysis TCGA data from 80 revealed RNA MTNR1A, retinoic acid-related orphan alpha (RORα), N-ribosyldihydronicotinamide:quinone oxidoreductase (NQO2), but not MTNR1B or G protein-coupled 50 (GPR50). Higher levels were observed a BRCA1 Associated Protein 1 (BAP1) mutation, NQO2 the epithelioid tumor cell type. However, Kaplan-Meier did show distinct survival probabilities based on expression. concludes that clinical samples express receptors, suggesting potential mechanism melatonin's effects. Despite finding died UM, no differences observed.

Language: Английский

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Evolutionary analysis of Quinone Reductases 1 and 2 suggests that NQO2 evolved to function as a pseudoenzyme

Protein Science, Journal Year: 2024, Volume and Issue: 33(12)

Published: Nov. 25, 2024

Abstract Quinone reductases 1 and 2 (NQO1 NQO2) are paralogous FAD‐linked enzymes found in all amniotes. NQO1 NQO2 have similar structures, both catalyze the reduction of quinones other electrophiles; however, two differ their cosubstrate preference. While can use redox couples NADH NADPH, is almost inactive with these cosubstrates instead must dihydronicotinamide riboside (NRH) small synthetic such as N‐ benzyl‐dihydronicotinamide (BNAH) for efficient catalysis. We used ancestral sequence reconstruction to investigate catalytic properties a predicted common ancestor additional ancestors from each evolutionary pathways extant NQO2. In cases, nicotinamide NRH BNAH were good along lineages. contrast, cosubstrate, evolved efficiency 100 times higher than ancestor, while has 3000 lower ancestor. The analysis combined site‐directed mutagenesis revealed potential site interaction ADP portion NAD(P)H that altered charge structure results indicate greater NAD(P)H, befitting an enzymatic function cells, was under selective pressure acquire extremely low NAD(P)H. These divergent trajectories implications functions enzymes.

Language: Английский

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Pharmacogenomics: Challenges and Future

Genes, Journal Year: 2024, Volume and Issue: 15(6), P. 714 - 714

Published: May 30, 2024

Over the last few decades, implementation of pharmacogenomics (PGx) in clinical practice has improved tailored drug prescriptions [...]

Language: Английский

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