A novel orally available Syk/Src/Jak2 inhibitor, SKLB-850, showed potent anti-tumor activities in B cell lymphoma (BCL) models
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Nannan Zhang1,*, Guo Zhang3,*, Ning Liu1,*, Wanting Lin1, Sen Ji1, Mingwu Zheng1, Kai Chen1, Xiao Liang1, Guobo Li1, Yu Ma4, Jun Zhu1, Ting Niu2, Lin-Li Li3, Jiong Li1, Yu-Quan Wei1 and Sheng-Yong Yang1
1National Center for Birth Defect Monitoring, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, West China Second University Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, 610041, China
2Department of Hematology & Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
3Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610041, China
4Department of Obstetric & Gynecologic, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
*These authors contributed equally to this work
Sheng-Yong Yang, email: firstname.lastname@example.org
Keywords: SKLB-850; B cell lymphoma; multikinase inhibitor
Received: September 19, 2017 Accepted: November 13, 2017 Published: December 01, 2017
B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as potential targets for the treatment of BCL. We have recently developed a multikinase inhibitor, SKLB-850, which potently inhibits Syk, Src, and JAK2. The aim of this study is to investigate the anti-BCL activities and mechanisms of action of SKLB-850 both in vitro and in vivo. Our results showed that SKLB-850 significantly inhibited BCL cell proliferation, and induced apoptosis of BCL cells. It could considerably decrease the secretion of chemokines CCL3, CCL4, and CXCL12. Oral administration of SKLB-850 considerably suppressed the tumor growth in BCL xenograft models (Ramos and HBL-1) in a dose-dependent manner. Immunohistochemistry of tumor tissues showed that SKLB-850 efficiently inhibited the activation of Syk/ERK, Src/FAK and JAK2/Stat3 pathways. Collectively, SKLB-850 could be a promising agent for the treatment of BCL, hence deserving further study.
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