Small-molecule binding of the axin RGS domain promotes β-catenin and Ras degradation

• Published in: Nature chemical biology Vol. 12; no. 8; pp. 593 - 600
• Main Authors: Cha, Pu-Hyeon, Cho, Yong-Hee, Lee, Sang-Kyu, Lee, JaeHeon, Jeong, Woo-Jeong, Moon, Byoung-San, Yun, Ji-Hye, Yang, Jee Sun, Choi, Sooho, Yoon, Juyong, Kim, Hyun-Yi, Kim, Mi-Yeon, Kaduwal, Saluja, Lee, Weontae, Min, Do Sik, Kim, Hoguen, Han, Gyoonhee, Choi, Kang-Yell
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2016
• Subjects: 49/47; 631/67/1059; 631/80/86; 631/92/507; 631/92/613; Animals; Axin Protein - chemistry; Axin Protein - metabolism; beta Catenin - chemistry; beta Catenin - metabolism; Binding Sites; Biochemical Engineering; Biochemistry; Bioorganic Chemistry; Cell Biology; Cell Proliferation - drug effects; Chemistry; Chemistry/Food Science; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Genes, APC; Genes, ras; Humans; Mice; Mice, Transgenic; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - genetics; Neoplasms, Experimental - pathology; Protein Stability - drug effects; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; RGS Proteins - chemistry; RGS Proteins - metabolism; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Thiohydantoins - chemical synthesis; Thiohydantoins - chemistry; Thiohydantoins - pharmacology; Wnt Signaling Pathway - drug effects

A small-molecule compound binds to the RGS domain of axin, promotes the degradation of β-catenin and Ras through the GSK3β-mediated destruction complex, and reduces the growth of KRAS and APC mutant colorectal cancer cell lines. Both the Wnt/β-catenin and Ras pathways are aberrantly activated in mos...