Lu, Xiaoxiao; Guan, Anqi; Chen, Xi; Xiao, Jian; Xie, Mingxuan; Yang, Baishuang; He, Shuya; You, Shaojin; Li, Wei; Chen, Qiong published an article in 2020, the title of the article was mPRa mediates P4/Org OD02-0 to improve the sensitivity of lung adenocarcinoma to EGFR-TKIs via the EGFR-SRC-ERK1/2 pathway.Synthetic Route of 380843-75-4 And the article contains the following content:
The discovery of epidermal growth factor receptor (EGFR) mutations has made EGFR tyrosine kinase inhibitors (EGFR-TKIs) a milestone in the treatment for advanced non-small cell lung cancer (NSCLC). However, patients lacking EGFR mutations are not sensitive to EGFR-TKI treatment and the emergence of secondary resistance poses new challenges for the targeted therapy of lung cancer. In this study, we identified that the expression of membrane progesterone receptor a (mPRa) was associated with EGFR mutations in lung adenocarcinoma patients and subsequently affected the efficacy of EGFR-TKIs. Progesterone (P4) or its derivative Org OD02-0 (Org), which is mediated by mPRa, increases the function of EGFR-TKIs to suppress the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. In addition, the mPRa pathway triggers delayed resistance to EGFR-TKIs. Mechanistic investigations demonstrated that the mPRa pathway can crosstalk with the EGFR pathway by activating nongenomic effects to inhibit the EGFR-SRC-ERK1/2 pathway, thereby promoting antitumorigenic effects. In conclusion, our data describe an essential role for mPRa in improving sensitivity to EGFR-TKIs, thus rationalizing its potential as a therapeutic target for lung adenocarcinomas. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Synthetic Route of 380843-75-4
The Article related to lung adenocarcinoma membrane progesterone receptor a egfr mutation, egfr mutations, egfr-tkis, lung adenocarcinoma, mprα, sensitivity, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Synthetic Route of 380843-75-4
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics