In Search for Inhibitors of Human Aldo-Keto Reductase 1B10 (AKR1B10) as Novel Agents to Fight Cancer and Chemoresistance: Current State-of-the-Art and Prospects

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

Aldo-keto reductase 1B10 (AKR1B10) is a human enzyme that catalyzes the NADPH-dependent reduction of several different carbonyl compounds to corresponding alcohols. Under physiological conditions, AKR1B10 expressed mainly in gastrointestinal tract, where it can detoxify reactive derived from dietary sources and xenobiotics. highly cancers precancerous proving be crucially implicated carcinogenesis function as prognostic indicator tumor development. Moreover, up-regulation strictly related acquired resistance known anticancer drugs. High levels this are also correlated pathogenesis noncancerous diseases, such skin pathologies COVID-19 complications. Therefore, last two decades, has attracted interest novel target for agents able fight both cancer chemoresistance, here, explored medicinal chemistry perspective.

Язык: Английский

The Role of Claudin-1 in Enhancing Pancreatic Cancer Aggressiveness and Drug Resistance via Metabolic Pathway Modulation

Cancers, Год журнала: 2025, Номер 17(9), С. 1469 - 1469

Опубликована: Апрель 27, 2025

Background/Objectives: Pancreatic ductal adenocarcinoma is a lethal malignancy, necessitating an understanding of its molecular mechanisms for the development new therapeutic strategies. The tight junction protein claudin-1, known to influence cellular functions in various cancers and considered target, remains unclear pancreatic cancer. Methods: This study assessed claudin-1 expression resected cancer samples, public databases, cell lines. Claudin-1 knockout with CRISPR/Cas9 on poorly differentiated lines proteome analysis were performed investigate intracellular claudin-1. Results: was markedly overexpressed intraepithelial neoplasia compared normal ducts, high levels independent predictor poor prognosis. diminished proliferation, migration, invasion, chemoresistance adenocarcinoma. Proteome revealed significant downregulation aldo-keto reductase family proteins (AKR1C2, AKR1C3, AKR1B1) cells, which are linked metabolic pathways. Aldo-keto knockdown reduced chemoresistance, invasion these Conclusions: These findings indicate that abnormal promotes tumor progression drug resistance through interaction proteins, highlighting as potential biomarkers targets

Язык: Английский

Multi-target anticancer activity of compounds isolated from galls of Pistacia chinensis subsp. integerrima: A mechanistic investigation

Phytochemistry Letters, Год журнала: 2024, Номер 64, С. 6 - 12

Опубликована: Сен. 19, 2024

Язык: Английский