1312692-95-7Relevant academic research and scientific papers
Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK)
Lam, Betty,Arikawa, Yasuyoshi,Cramlett, Joshua,Dong, Qing,de Jong, Ron,Feher, Victoria,Grimshaw, Charles E.,Farrell, Pamela J.,Hoffman, Isaac D.,Jennings, Andy,Jones, Benjamin,Matuszkiewicz, Jennifer,Miura, Joanne,Miyake, Hiroshi,Natala, Srinivasa Reddy,Shi, Lihong,Takahashi, Masashi,Taylor, Ewan,Wyrick, Corey,Yano, Jason,Zalevsky, Jonathan,Nie, Zhe
supporting information, p. 5947 - 5950 (2016/12/06)
Spleen Tyrosine Kinase (SYK) is a non-receptor cytoplasmic tyrosine kinase that is primarily expressed in hematopoietic cells. SYK is a key mediator for a variety of inflammatory cells, including B cells, mast cells, macrophages and neutrophils and therefore, an attractive approach for treatment of both inflammatory diseases and oncology indications. Using in house co-crystal structure information, and structure-based drug design, we designed and optimized a novel series of heteroaromatic pyrrolidinone SYK inhibitors resulting in the selection of the development candidate TAK-659. TAK-659 is currently undergoing Phase I clinical trials for advanced solid tumor and lymphoma malignancies, a Phase Ib study in advanced solid tumors in combination with nivolumab, and PhIb/II trials for relapsed/refractory AML.
