4N6Y

Pim1 Complexed with a phenylcarboxamide

4N6Y の概要

• エントリーDOI: 10.2210/pdb4n6y/pdb
• 関連するPDBエントリー: 4N6Z 4N70
• 分子名称: Serine/threonine-protein kinase pim-1, 2-(acetylamino)-N-[2-(piperidin-1-yl)phenyl]-1,3-thiazole-4-carboxamide (3 entities in total)
• 機能のキーワード: kinase, phosphorylation, 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: 37941.13

構造登録者

Bellamacina, C.R.,Le, V.,Shu, W.,Burger, M.T.,Bussiere, D. (登録日: 2013-10-14, 公開日: 2013-11-06, 最終更新日: 2024-11-06)

主引用文献

Burger, M.T.,Han, W.,Lan, J.,Nishiguchi, G.,Bellamacina, C.,Lindval, M.,Atallah, G.,Ding, Y.,Mathur, M.,McBride, C.,Beans, E.L.,Muller, K.,Tamez, V.,Zhang, Y.,Huh, K.,Feucht, P.,Zavorotinskaya, T.,Dai, Y.,Holash, J.,Castillo, J.,Langowski, J.,Wang, Y.,Chen, M.Y.,Garcia, P.D.
Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM Kinase Inhibitors.
ACS Med Chem Lett, 4:1193-1197, 2013

PubMed Abstract: Proviral insertion of Moloney virus (PIM) 1, 2, and 3 kinases are serine/threonine kinases that normally function in survival and proliferation of hematopoietic cells. As high expression of PIM1, 2, and 3 is frequently observed in many human malignancies, including multiple myeloma, non-Hodgkins lymphoma, and myeloid leukemias, there is interest in determining whether selective PIM inhibition can improve outcomes of these human cancers. Herein, we describe our efforts toward this goal. The structure guided optimization of a singleton high throughput screening hit in which the potency against all three PIM isoforms was increased >10,000-fold to yield compounds with pan PIM K is < 10 pM, nanomolar cellular potency, and in vivo activity in an acute myeloid leukemia Pim-dependent tumor model is described.

PubMed: 24900629
DOI: 10.1021/ml400307j

実験手法

X-RAY DIFFRACTION (2.6 Å)