1286264-27-4Relevant academic research and scientific papers
Discovery of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs
Nakao, Akira,Suzuki, Hiroko,Ueno, Hiroaki,Iwasaki, Hiroshi,Setsuta, Tomofumi
, p. 4336 - 4340 (2014)
High throughput screening using Automated Ligand Identification System (ALIS) resulted in the discovery of a new series of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs. The optimization campaign led to very potent and competitive compound 39 with a Ki value of 1.5 nM. Compound 39 could be a promising lead compound for research to reduce elevated homocysteine levels.
Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs
Nakao, Akira,Suzuki, Hiroko,Ueno, Hiroaki,Iwasaki, Hiroshi,Setsuta, Tomofumi,Kashima, Akiko,Sunada, Shinji
, p. 4952 - 4969 (2015/08/03)
Optimization of a new series of S-adenosyl-l-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 ± 3, 5.0 ± 2.0, and 8.5 ± 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD+ and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction.
