6NO9

PIM1 in complex with Cpd16 (5-amino-N-(5-((4R,5R)-4-amino-5-fluoroazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide)

6NO9 の概要

• エントリーDOI: 10.2210/pdb6no9/pdb
• 分子名称: Serine/threonine-protein kinase pim-1, GLYCEROL, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32265.33

構造登録者

Murray, J.M.,Noland, C. (登録日: 2019-01-15, 公開日: 2019-02-27, 最終更新日: 2023-10-11)

主引用文献

Wang, X.,Blackaby, W.,Allen, V.,Chan, G.K.Y.,Chang, J.H.,Chiang, P.C.,Diene, C.,Drummond, J.,Do, S.,Fan, E.,Harstad, E.B.,Hodges, A.,Hu, H.,Jia, W.,Kofie, W.,Kolesnikov, A.,Lyssikatos, J.P.,Ly, J.,Matteucci, M.,Moffat, J.G.,Munugalavadla, V.,Murray, J.,Nash, D.,Noland, C.L.,Del Rosario, G.,Ross, L.,Rouse, C.,Sharpe, A.,Slaga, D.,Sun, M.,Tsui, V.,Wallweber, H.,Yu, S.F.,Ebens, A.J.
Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma.
J. Med. Chem., 62:2140-2153, 2019

PubMed Abstract: Pim kinases have been targets of interest for a number of therapeutic areas. Evidence of durable single-agent efficacy in human clinical trials validated Pim kinase inhibition as a promising therapeutic approach for multiple myeloma patients. Here, we report the compound optimization leading to GDC-0339 (16), a potent, orally bioavailable, and well tolerated pan-Pim kinase inhibitor that proved efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models and has been evaluated as an early development candidate.

PubMed: 30715878
DOI: 10.1021/acs.jmedchem.8b01857

実験手法

X-RAY DIFFRACTION (1.712 Å)