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J Drug Target. 2018 Oct 30:1-9. doi: 10.1080/1061186X.2018.1533964. [Epub ahead of print]

GZD2202, a novel TrkB inhibitor, suppresses BDNF-mediated proliferation and metastasis in neuroblastoma models.

Zou J1, Zhang Z2,3, Xu F2,3, Cui S4,5, Qi C6, Luo J5, Wang Z4,5, Lu X2,3, Tu Z1,5, Ren X2,3, Song L1, Ding K2,3.

Author information

1
a School of Pharmacy , Jinan University , Guangzhou , China.
2
b International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), School of Pharmacy , Jinan University , Guangzhou , China.
3
c Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy , Jinan University , Guangzhou , China.
4
d University of Chinese Academy of Sciences , Beijing , China.
5
e Guangzhou Institutes of Biomedicine and Health , Chinese Academy of Sciences , Guangzhou , China.
6
f Insititute of Laboratory Animal Science , Jinan University , Guangzhou , China.

Abstract

Collective data suggest tropomyosin-related kinase B (TrkB), which is correlated with the growth, migration and poor prognosis of neuroblastoma (NB), is a potential target for NB target therapy. Several Phase I/II pan-Trk inhibitors display impressive clinical outcomes but still no drug has been approved for general use. In this paper, we report a novel structural TrkB inhibitor GZD2202, a structural derivative of our previously identified DDR1 antagonists. GZD2202 demonstrates a moderate selectivity between Trk B/C and TrkA. GZD2202 suppresses the brain-derived neurotrophic factor (BDNF) -mediated TrkB signalling pathway, proliferation, migration and invasion in SH-SY5Y-TrkB neuroblastoma cells, and causes about 36.1% growth inhibition in a SH-SY5Y-TrkB neuroblastoma xenograft model.

KEYWORDS:

BDNF; GZD2202; Tropomyosin receptor kinase B; neuroblastoma

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