4KZC

Structure of PI3K gamma with Imidazopyridine inhibitors

4KZC の概要

• エントリーDOI: 10.2210/pdb4kzc/pdb
• 関連するPDBエントリー: 4KZ0
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, N-{6-[6-amino-5-(trifluoromethyl)pyridin-3-yl]imidazo[1,2-a]pyridin-2-yl}acetamide, SULFATE ION (3 entities in total)
• 機能のキーワード: lipid kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P48736
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 111187.51

構造登録者

Knapp, M.S.,Elling, E.A. (登録日: 2013-05-29, 公開日: 2013-07-17, 最終更新日: 2024-02-28)

主引用文献

Pecchi, S.,Ni, Z.J.,Han, W.,Smith, A.,Lan, J.,Burger, M.,Merritt, H.,Wiesmann, M.,Chan, J.,Kaufman, S.,Knapp, M.S.,Janssen, J.,Huh, K.,Voliva, C.F.
Structure guided optimization of a fragment hit to imidazopyridine inhibitors of PI3K.
Bioorg.Med.Chem.Lett., 23:4652-4656, 2013

PubMed Abstract: PI3 kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation. The PI3 Kinase pathway is often de-regulated in cancer through PI3Kα overexpression, gene amplification, mutations and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe how the potency of a benzothiazole fragment hit was quickly improved based on structural information and how this early chemotype was further optimized through scaffold hopping. This effort led to the identification of a series of 2-acetamido-5-heteroaryl imidazopyridines showing potent in vitro activity against all class I PI3Ks and attractive pharmacokinetic properties.

PubMed: 23820386
DOI: 10.1016/j.bmcl.2013.06.010

実験手法

X-RAY DIFFRACTION (3.25 Å)