Research Papers:

Docking of THPDTPI: to explore P-selectin as a common target of anti-tumor, anti-thrombotic and anti-inflammatory agent

Haimei Zhu, Yuji Wang, Ce Song, Qiqi Feng, Jianhui Wu, Shurui Zhao, Lin Gui, Xiaoyi Zhang, Ming Zhao _ and Shiqi Peng

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Oncotarget. 2018; 9:268-281. https://doi.org/10.18632/oncotarget.19374

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Haimei Zhu1,2,3, Yuji Wang1,2,4, Ce Song6, Qiqi Feng1,2,3, Jianhui Wu1,2,4, Shurui Zhao1,2,3, Lin Gui1,2,4, Xiaoyi Zhang1,2,4, Ming Zhao1,2,4,5 and Shiqi Peng1,2,4

1College of Pharmaceutical Sciences of Capital Medical University, Beijing, China

2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, China

3Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, China

4Beijing Laboratory of Biomedical Materials, Beijing, China

5Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan

6Guangxi Pusen Biotechnology Co. Ltd., Guilin, China

Correspondence to:

Ming Zhao, email: [email protected]

Ce Song, email: [email protected]

Shiqi Peng, email: [email protected]

Keywords: P-selectin, anti-tumor, anti-thrombosis, anti-inflammation, target

Received: February 06, 2017     Accepted: July 06, 2017     Published: July 19, 2017


The impact of soluble P-selectin on tumor growth, thrombosis and inflammation has been individually documented. Whether the down-regulation of P-selectin expression can simultaneously slow the tumor growth, inhibit the thrombosis and attenuate the inflammatory response remains unknown. In this context, (2′S,5′S)- tetrahydropyrazino[1’,2’:1,6]-di{2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole}-1’,4’-dione (THPDTPI) was designed as an inhibitor of P-selectin. The suitable docking of THPDTPI towards the active site of P-selectin, the significant down-regulation of THPDTPI to P-selectin expression, and the direct action of THPDTPI on P-selectin suggest that P-selectin could be a target of THPDTPI. In vivo THPDTPI possesses the anti-tumor activity, the anti-thrombotic activity and the anti-inflammatory activity. This implies that targeting P-selectin is of essential importance for this triple activity. The minimal effective doses of THPDTPI inhibiting the tumor growth, the rat arterial thrombosis and the mouse ear edema are 0.01 μmol/kg, 0.1 μmol/kg and 0.001 μmol/kg, respectively. Atomic force microscopy images and FT-MS spectra showed that the adhesion of THPDTPI onto the surfaces of the platelets may be the first step of P-selectin targeting. Besides, the dependence of the triple action of THPDTPI inhibiting the tumor growth, the thrombosis and the inflammation on the decrease of the soluble P-selectin led to the correlation of the soluble P-selectin with the serum TNF-α and serum IL-8.

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