3HDM

Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 1

3HDM の概要

• エントリーDOI: 10.2210/pdb3hdm/pdb
• 関連するPDBエントリー: 3HDN
• 分子名称: Serine/threonine-protein kinase Sgk1, 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (3 entities in total)
• 機能のキーワード: agc protein kinase, apoptosis, atp-binding, endoplasmic reticulum, nucleotide-binding, nucleus, phosphorylation, serine/threonine-protein kinase, transferase, kinase, phosphoprotein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 2: Cell membrane. Cytoplasm: O00141
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42617.66

構造登録者

Zhao, B.,Hammond, M. (登録日: 2009-05-07, 公開日: 2009-06-30, 最終更新日: 2024-11-06)

主引用文献

Hammond, M.,Washburn, D.G.,Hoang, H.T.,Manns, S.,Frazee, J.S.,Nakamura, H.,Patterson, J.R.,Trizna, W.,Wu, C.,Azzarano, L.M.,Nagilla, R.,Nord, M.,Trejo, R.,Head, M.S.,Zhao, B.,Smallwood, A.M.,Hightower, K.,Laping, N.J.,Schnackenberg, C.G.,Thompson, S.K.
Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors.
Bioorg.Med.Chem.Lett., 19:4441-4445, 2009

PubMed Abstract: The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing.

PubMed: 19497745
DOI: 10.1016/j.bmcl.2009.05.051

実験手法

X-RAY DIFFRACTION (2.6 Å)