6530-41-2Relevant academic research and scientific papers
Design, Synthesis, and Evaluation of Small Molecule Gαq/11 Protein Inhibitors for the Treatment of Uveal Melanoma
Ge, Yang,Shi, Shuo,Deng, Jun-Jie,Chen, Xue-Ping,Song, Zhendong,Liu, Lu,Lou, Linlin,Zhang, Xiaolei,Xiong, Xiao-Feng
, p. 3131 - 3152 (2021/04/12)
Uveal melanoma is the ocular malignancy and mainly driven by oncogenic mutations of Gαq/11 proteins. Previous targeted therapy for melanoma treatment was limited to specific downstream signaling pathway, and inhibiting the "molecular switches"G proteins for melanoma treatment therapy was rarely described. We herein report the discovery of imidazopiperazine derivatives as Gαq/11 protein inhibitors. The most promising compound GQ127 showed good efficacy and safety in inositol monophosphate (IP1) assay by directly inhibiting Gαq/11 proteins. GQ127 induced uveal melanoma cells apoptosis and displayed potent antitumor activities in uveal melanoma cells viability, migration, and invasion. The effects of GQ127 on Gαq/11 signaling pathway were confirmed by analyzing the downstream effectors yes-associated protein (YAP) and extracellular signal-regulated kinase (ERK). More importantly, GQ127 significantly suppressed UM xenograft growth in mouse model without severe toxicity at the testing dose. These findings provide a lead compound that directly targets the Gαq/11 proteins for uveal melanoma treatment.
Broadening of the substrate tolerance of α-chymotrypsin by using the carbamoylmethyl ester as an acyl donor in kinetically controlled peptide synthesis
Miyazawa, Toshifumi,Tanaka, Kayoko,Ensatsu, Eiichi,Yanagihara, Ryoji,Yamada, Takashi
, p. 87 - 93 (2007/10/03)
In the kinetically controlled approach of peptide synthesis mediated by α-chymotrypsin, the broadening of the protease's substrate tolerance is achieved by switching the acyl donor from the conventional methyl ester to the carbamoylmethyl ester. Thus, as a typical example, the extremely low coupling efficiency obtained by employing the methyl ester of an inherently poor amino acid substrate, Ala, is significantly improved by the use of this particular ester. Its ameliorating effect is observed also in the couplings of other amino acid residues such as Gly and Ser as carboxy components.
Etude de la stereochimie de la reaction de cycloaddition dipolaire-1,3 de quelques 5-phenyl-3,6-dihydro-2H-1,4-oxazin-2-ones avec les N-methyl et N-phenylmaleimides
Monnier, Karin,Schmitt, Gerard,Laude, Bernard,Mercier, Marie-France,Kubicki, Marek M.,Jannin, Michel
, p. 181 - 190 (2007/10/02)
Six derivatives of 5-phenyl-3,4-dihydro-2H-1,4-oxazin-2-ones 1 were synthetized from α-amino acids.These compounds are precursors of six-membered cyclic azomethine ylids involving one stereocenter.The 1,3-dipolar species react with N-methyl and N-phenylma
