4XHK

PIM1 kinase in complex with Compound 1s

4XHK の概要

• エントリーDOI: 10.2210/pdb4xhk/pdb
• 関連するPDBエントリー: 4X7Q
• 分子名称: Serine/threonine-protein kinase pim-1, 2-(2,6-difluorophenyl)-N-{4-[(3S)-pyrrolidin-3-yloxy]pyridin-3-yl}-1,3-thiazole-4-carboxamide (3 entities in total)
• 機能のキーワード: transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36369.31

構造登録者

Marcotte, D.J.,Silvian, L.F. (登録日: 2015-01-05, 公開日: 2015-02-11, 最終更新日: 2024-10-16)

主引用文献

Ishchenko, A.,Zhang, L.,Le Brazidec, J.Y.,Fan, J.,Chong, J.H.,Hingway, A.,Raditsis, A.,Singh, L.,Elenbaas, B.,Hong, V.S.,Marcotte, D.,Silvian, L.,Enyedy, I.,Chao, J.
Structure-based design of low-nanomolar PIM kinase inhibitors.
Bioorg.Med.Chem.Lett., 25:474-480, 2015

PubMed Abstract: PIM kinases are implicated in variety of cancers by promoting cell survival and proliferation and are targets of interest for therapeutic intervention. We have identified a low-nanomolar pan-PIM inhibitor (PIM1/2/3 potency 5:14:2nM) using structure based modeling. The crystal structure of this compound with PIM1 confirmed the predicted binding mode and protein-ligand interactions except those in the acidic ribose pocket. We show the SAR suggesting the importance of having a hydrogen bond donor in this pocket for inhibiting PIM2; however, this interaction is not important for inhibiting PIM1 or PIM3. In addition, we report the discovery of a new class of PIM inhibitors by using computational de novo design tool implemented in MOE software (Chemical Computing Group). These inhibitors have a different interaction profile.

PubMed: 25575657
DOI: 10.1016/j.bmcl.2014.12.041

実験手法

X-RAY DIFFRACTION (1.9 Å)