CDK4/6 inhibitors downregulate the ubiquitin-conjugating enzymes UBE2C/S/T involved in the ubiquitin-proteasome pathway in ER + breast cancer was written by Lin, Chih-Yi;Yu, Chung-Jen;Liu, Chun-Yu;Chao, Ta-Chung;Huang, Chi-Cheng;Tseng, Ling-Ming;Lai, Jiun-I.. And the article was included in Clinical and Translational Oncology in 2022.Related Products of 1211441-98-3 This article mentions the following:
Abstract: Despite significant improvement in therapeutic development in the past decades, breast cancer remains a formidable cause of death for women worldwide. The hormone pos. subtype (HR( +)) (also known as luminal type) is the most prevalent category of breast cancer, comprising 鈭?70% of patients. The clin. success of the three CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib has revolutionized the treatment of choice for metastatic HR( +) breast cancer. Accumulating evidence demonstrate that the properties of CDK4/6 inhibitors extend beyond inhibition of the cell cycle, including modulation of immune function, sensitizing PI3K inhibitors, metabolism reprogramming, kinome rewiring, modulation of the proteasome, and many others. The ubiquitin-proteasome pathway (UPP) is a crucial cellular proteolytic system that maintains the homeostasis and turnover of proteins. By transcriptional profiling of the HR( +) breast cancer cell lines MCF7 and T47D treated with Palbociclib, we have uncovered a novel mechanism that demonstrates that the CDK4/6 inhibitors suppress the expression of three ubiquitin-conjugating enzymes UBE2C, UBE2S, UBE2T. Further validation in the HR( +) cell lines show that Palbociclib and ribociclib decrease UBE2C at both the mRNA and protein level, but this phenomenon was not shared with abemaciclib. These three E2 enzymes modulate several E3 ubiquitin ligases, including the APC/C complex which plays a role in G1/S progression. We further demonstrate that the UBE2C/UBE2T expression levels are associated with breast cancer survival, and HR( +) breast cancer cells demonstrate dependence on the UBE2C. Our study suggests a novel link between CDK4/6 inhibitor and UPP pathway, adding to the potential mechanisms of their clin. efficacy in cancer. 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: 1211441-98-3Related Products of 1211441-98-3).
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. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 掳C and boils at 125鈥?30 掳C. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Related Products of 1211441-98-3
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Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics