Xu, Zhixiang; Xu, Xiangxiang; O’Laoi, Ruadhan; Ma, Haikuo; Zheng, Jiyue; Chen, Shuaishuai; Luo, Lusong; Hu, Zhilin; He, Sudan; Li, Jiajun; Zhang, Hongjian; Zhang, Xiaohu published the artcile< Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold>, Formula: C12H18BNO2, the main research area is Wnt3A inhibitor amide scaffold; Antagonist; Cancer therapy; Porcupine; Scaffold hybridization; Wnt signaling pathway.
The Wnt signaling pathway is an essential signal transduction pathway which leads to the regulation of cellular processes such as proliferation, differentiation and migration. Aberrant Wnt signaling is known to have an association with multiple cancers. Porcupine is an enzyme that catalyzes the addition of palmitoleate to a serine residue in Wnt proteins, a process which is required for the secretion of Wnt proteins. Here the authors report the synthesis and structure-activity-relationship of the novel porcupine inhibitors based on a ‘reversed’ amide scaffold. The leading compound I was as potent as the clin. compound LGK974 in a cell based STF reporter gene assay. Compound I potently inhibited the secretion of Wnt3A, therefore was confirmed to be a porcupine inhibitor. Furthermore, compound I showed excellent chem. and plasma stabilities. However, the clearance of compound I in liver microsomal tests was moderate to high, and the solubility of compound I was suboptimal. Collective efforts toward further optimization of this novel tricyclic template to develop better porcupine inhibitors will be subsequently undertaken and reported in due course.
Bioorganic & Medicinal Chemistry published new progress about Homo sapiens. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Formula: C12H18BNO2.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts