Chemoproteomics of Marine Natural Product Naamidine J Unveils CSE1L as a Therapeutic Target in Acute Lung Injury

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Acute lung injury is a devastating illness characterized by severe inflammation mediated aberrant activation of macrophages, resulting in significant morbidity and mortality, highlighting the urgent need for novel pharmacological targets drug candidates. In this study, we identified target regulating macrophages acute via chemical proteomics genetics based on marine alkaloid, naamidine J (NJ). The structures NJ-related alkaloids were first confirmed or revised combination quantum calculations X-ray diffraction analysis. NJ was found as potential anti-inflammatory agent screening our compound library, CSE1L chemoproteomics main cellular to inhibit protect against injury. Mechanistically, demonstrated that directly interacted with sites His745 Phe903 then inhibited nuclear translocation transcriptional activity transcription factor SP1, thereby suppressing ameliorating Taken together, these findings have uncovered treatment also provided druggable pocket lead an available tool from sources investigating function developing candidates

Язык: Английский

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Glochodpurnoid B from Glochidion puberum Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Colorectal Cancer Cells

Molecules, Год журнала: 2023, Номер 28(2), С. 511 - 511

Опубликована: Янв. 4, 2023

Glochidpurnoids A and B (1 2), two new coumaroyl or feruloyl oleananes, along with 17 known triterpenoids (3-19) were obtained from the stems twigs of Glochidion puberum. Their structures elucidated by extensive spectroscopic data analyses, chemical methods, single crystal X-ray diffraction. All compounds screened for cytotoxicity against colorectal cancer cell line HCT-116, 2, 3, 5, 6, 11, showed remarkable inhibitory activities (IC50: 0.80-2.99 μM), being more active than positive control 5-fluorouracil (5-FU). The mechanistic study most potent compound, that it could induce endoplasmic reticulum (ER) stress-mediated apoptosis improve sensitivity HCT-116 cells to 5-FU.

Язык: Английский

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Antiproliferative effects of resorcylic acid lactones from the Beibu Gulf coral-derived fungus Curvularia lunata GXIMD 02512 on prostate cancer cells

RSC Advances, Год журнала: 2024, Номер 14(52), С. 38697 - 38705

Опубликована: Янв. 1, 2024

Four novel resorcylic acid lactones (RALs), curvulomycins A-D (1-4), and six known congeners were isolated from the Beibu Gulf coral-derived fungus

Язык: Английский

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DHODH inhibition represents a therapeutic strategy and improves abiraterone treatment in castration-resistant prostate cancer

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 25, 2023

Abstract Castration-resistant prostate cancer (CRPC) is an aggressive disease with poor prognosis, and there urgent need for more effective therapeutic targets to address this challenge. Here, we showed that Dihydroorotate dehydrogenase (DHODH), enzyme crucial in the pyrimidine biosynthesis pathway, a promising target CRPC. The transcript levels of DHODH were significantly elevated tumors negatively correlated prognosis patients cancer. inhibition effectively suppressed CRPC progression by blocking cell cycle inducing apoptosis. Notably, treatment BAY2402234 activated androgen signaling cells. However, combination abiraterone decreased intratumoral testosterone induced apoptosis, which inhibited growth CWR22Rv1 xenograft patient-derived organoids. Taken together, these results establish as key player potential advanced

Язык: Английский

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Discovery of a Potent Importin Inhibitor for Cancer Treatment

Synfacts, Год журнала: 2022, Номер 18(12), С. 1369 - 1369

Опубликована: Ноя. 17, 2022

Key words importin inhibitors - castration-resistant prostate cancer (CRPC) daphnane diterpenoids (DDs)

Язык: Английский

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