Work

A novel orally available Syk/Src/Jak2 inhibitor, SKLB-850, showed potent anti-tumor activities in B cell lymphoma (BCL) models

Year: 2017

Type: article

Abstract: // Nannan Zhang 1, * , Guo Zhang 3, * , Ning Liu 1, * , Wanting Lin 1 , Sen Ji 1 , Mingwu Zheng 1 , Kai Chen 1 , Xiao Liang 1 , Guobo Li 1 , Yu Ma 4 , Jun Zhu 1 , Ting Niu 2 , Lin-Li Li 3 , Jiong Li 1 , Yu-Quan Wei 1 and Sheng-Yong Yang 1 1 National 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 2 Department of Hematology & Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China 3 Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610041, China 4 Department of Obstetric & Gynecologic, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China * These authors contributed equally to this work Correspondence to: Sheng-Yong Yang, email: [email protected] Keywords: SKLB-850; B cell lymphoma; multikinase inhibitor Received: September 19, 2017 Accepted: November 13, 2017 Published: December 01, 2017 ABSTRACT 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.22847