Academic Journal
Discovery of Novel Aminobutanoic Acid-Based ASCT2 Inhibitors for the Treatment of Non-Small-Cell Lung Cancer
| العنوان: | Discovery of Novel Aminobutanoic Acid-Based ASCT2 Inhibitors for the Treatment of Non-Small-Cell Lung Cancer |
|---|---|
| المؤلفون: | Lian Qin, Xinying Cheng, Shijiao Wang, Guangyue Gong, Huiyan Su, Huidan Huang, Tian Chen, Davaadagva Damdinjav, Buyankhishig Dorjsuren, Zhiyu Li, Zhixia Qiu, Jinlei Bian |
| سنة النشر: | 1753 |
| مصطلحات موضوعية: | Biochemistry, Medicine, Microbiology, Cell Biology, Molecular Biology, Pharmacology, Biotechnology, Cancer, Hematology, Infectious Diseases, Space Science, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, suppressed mtor signaling, promising therapeutic agents, effectively blocking glutamine, cysteine transporter 2, could potentially lead, v9302 , potent asct2 inhibitors, based asct2 inhibitors, asct2 inhibitors based, 25e , 20k , tumor growth inhibition, suppressed tumor growth, cell lung cancer, a549 xenograft model, 50 , novel aminobutanoic acid |
| الوصف: | Alanine-serine-cysteine transporter 2 (ASCT2) is up-regulated in lung cancers, and inhibiting it could potentially lead to nutrient deprivation, making it a viable strategy for cancer treatment. In this study, we present a series of ASCT2 inhibitors based on aminobutanoic acids, which exhibit potent inhibitory activity. Two compounds, 20k and 25e , were identified as novel and potent ASCT2 inhibitors, with IC 50 values at the micromolar level in both A549 and HEK293 cells, effectively blocking glutamine (Gln) uptake. Additionally, these compounds regulated amino acid metabolism, suppressed mTOR signaling, inhibited non-small-cell lung cancer (NSCLC) growth, and induced apoptosis. In vivo, experiments showed that 20k and 25e suppressed tumor growth in an A549 xenograft model, with tumor growth inhibition (TGI) values of 65 and 70% at 25 mg/kg, respectively, while V9302 only achieved a TGI value of 29%. Furthermore, both compounds demonstrated promising therapeutic potential in patient-derived organoids. Therefore, these ASCT2 inhibitors based on aminobutanoic acids are promising therapeutic agents for treating NSCLC by targeting cancer Gln metabolism. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/journal_contribution/Discovery_of_Novel_Aminobutanoic_Acid-Based_ASCT2_Inhibitors_for_the_Treatment_of_Non-Small-Cell_Lung_Cancer/24994546 |
| DOI: | 10.1021/acs.jmedchem.3c01093.s001 |
| الاتاحة: | https://doi.org/10.1021/acs.jmedchem.3c01093.s001 https://figshare.com/articles/journal_contribution/Discovery_of_Novel_Aminobutanoic_Acid-Based_ASCT2_Inhibitors_for_the_Treatment_of_Non-Small-Cell_Lung_Cancer/24994546 |
| Rights: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.523383C0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.3c01093.s001 |
|---|