Identification of structurally diverse growth hormone secretagogue agonists by virtual screening and structure-activity relationship analysis of 2-formylaminoacetamide derivatives.
Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays. These compounds were structurally diverse and significantly differed from known GHS agonists. The most active compound was subjected to SAR evaluation, which slightly increased its potency and identified molecular regions important for specific GHS agonist activity.
Shoda
Miyuki
M
Laboratory for Medicinal Chemistry, Institute for Life Science Research, Asahi Kasei Pharma, 632-1 Mifuku, Ohito, Tagata, Shizuoka, Japan.
Harada
Takeo
T
Kogami
Yuji
Y
Tsujita
Ryuichi
R
Akashi
Hirotada
H
Kouji
Hiroyuki
H
Stahura
Florence L
FL
Xue
Ling
L
Bajorath
Jürgen
J
D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003198:Computer Simulation; D005559:Formamides / Q000737:chemistry* / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000819:agonists* / Q000737:chemistry; D006801:Humans; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
D000081:Acetamides; D005559:Formamides; D013007:Growth Hormone-Releasing Hormone; D002118:Calcium