Ribociclib inhibits P-gp-mediated multidrug resistance in human epidermoid carcinoma cells was written by Zhang, Lei;Ye, Biwei;Lin, Yunfeng;Li, Yi-Dong;Wang, Jing-Quan;Chen, Zhuo;Ping, Feng-Feng;Chen, Zhe-Sheng. And the article was included in Frontiers in Pharmacology in 2022.Synthetic Route of C23H30N8O This article mentions the following:
The efficacy of cancer chemotherapy can be attenuated or abrogated by multidrug resistance (MDR) in cancer cells. In this study, we determined the effect of the CDK4/6 inhibitor, ribociclib (or LEE011), on P-glycoprotein (P-gp)-mediated MDR in the human epidermoid carcinoma MDR cell line, KB-C2, which is widely used for studying P-gpmediated MDR in cancers. The incubation of KB-C2 cells with ribociclib (3-9μM) increased the efficacy of colchicine, a substrate for P-gp. The cell expression of P-gp was downregulated at both translation and transcription levels. Furthermore, ribociclib produced a 3.5-fold increase in the basal activity of P-gp ATPase, and the concentration required to increase basal activity by 50% (EC50) was 0.04μM. Docking studies indicated that ribociclib interacted with the drug-substrate binding site of P-gp. The short-term and long-term intracellular accumulation of doxorubicin greatly increased in the KB-C2 cells cocultured with ribociclib, indicating ribociclib inhibited the drug efflux activity of P-gp. The results of our study indicate that LEE011 may be a potential agent for combined therapy of the cancers with P-gp mediated MDR. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Synthetic Route of C23H30N8O).
7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Synthetic Route of C23H30N8O
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics