On November 30, 2021, Liu, Zhen-zhen; Liu, Xiao-ning; Fan, Rui-cheng; Jia, Yu-ping; Zhang, Qing-ke; Gao, Xin-qing; Wang, Yu-qing; Yang, Meng-qing; Ji, Li-zhen; Zhou, Yong-qing; Li, Hong-li; Li, Ping; Tang, Bo published an article.Recommanded Product: 73590-85-9 The title of the article was Identification of pimavanserin tartrate as a potent Ca2+-calcineurin-NFAT pathway inhibitor for glioblastoma therapy. And the article contained the following:
Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor, and 95% of patients die within 2 years after diagnosis. In this study, aiming to overcome chemoresistance to the first-line drug temozolomide (TMZ), we carried out research to discover a novel alternative drug targeting the oncogenic NFAT signaling pathway for GBM therapy. To accelerate the drug鈥瞫 clin. application, we took advantage of a drug repurposing strategy to identify novel NFAT signaling pathway inhibitors. After screening a set of 93 FDA-approved drugs with simple structures, we identified pimavanserin tartrate (PIM), an effective 5-HT2A receptor inverse agonist used for the treatment of Parkinson鈥瞫 disease-associated psychiatric symptoms, as having the most potent inhibitory activity against the NFAT signaling pathway. Further study revealed that PIM suppressed STIM1 puncta formation to inhibit store-operated calcium entry (SOCE) and subsequent NFAT activity. In cellula, PIM significantly suppressed the proliferation, migration, division, and motility of U87 glioblastoma cells, induced G1/S phase arrest and promoted apoptosis. In vivo, the growth of s.c. and orthotopic glioblastoma xenografts was markedly suppressed by PIM. Unbiased omics studies revealed the novel mol. mechanism of PIM鈥瞫 antitumor activity, which included suppression of the ATR/CDK2/E2F axis, MYC, and AuroraA/B signaling. Interestingly, the genes upregulated by PIM were largely associated with cholesterol homeostasis, which may contribute to PIM鈥瞫 side effects and should be given more attention. Our study identified store-operated calcium channels as novel targets of PIM and was the first to systematically highlight the therapeutic potential of pimavanserin tartrate for glioblastoma. The experimental process involved the reaction of 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]thio]benzimidazole(cas: 73590-85-9).Recommanded Product: 73590-85-9
The Article related to pimavanserin tartrate calcium calcineurin nfat inhibitor glioblastoma therapy, nfat signaling pathway, soce, drug repurposing, glioblastoma, pimavanserin tartrate, Placeholder for records without volume info and other aspects.Recommanded Product: 73590-85-9
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem