Principe, Daniel R.’s team published research in Proceedings of the National Academy of Sciences of the United States of America in 119 | CAS: 21829-25-4

Proceedings of the National Academy of Sciences of the United States of America published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Principe, Daniel R. published the artcileCalcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Proceedings of the National Academy of Sciences of the United States of America (2022), 119(18), e2200143119, database is CAplus and MEDLINE.

There is currently no effective treatment for pancreatic ductal adenocarcinoma (PDAC). While palliative chemotherapy offers a survival benefit to most patients, nearly all will eventually progress on treatment and long-term survivability remains poor. Given the lack of subsequent line treatment options, in this study, we sought to identify novel strategies to prevent, delay, or overcome resistance to gemcitabine, one of the most widely used medications in PDAC. Using a combination of single-cell RNA sequencing and high-throughput proteomic anal., we identified a subset of gemcitabine-resistant tumor cells enriched for calcium/calmodulin signaling. Pharmacol. inhibition of calcium-dependent calmodulin activation led to the rapid loss of drug-resistant phenotypes in vitro, which addnl. single-cell RNA sequencing identified was due to impaired activation of the RAS/ERK signaling pathway. Consistent with these observations, calcium chelation or depletion of calcium in the culture media also impaired ERK activation in gemcitabine-resistant cells, and restored therapeutic responses to gemcitabine in vitro. We observed similar results using calcium channel blockers (CCBs) such as amlodipine, which inhibited prosurvival ERK signaling in vitro and markedly enhanced therapeutic responses to gemcitabine in both orthotopic xenografts and transgenic models of PDAC. Combined, these results offer insight into a potential means of gemcitabine resistance and suggest that select CCBs may provide a clin. benefit to PDAC patients receiving gemcitabine-based chemotherapy.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem