Next Article in Journal
α-Difluoromethylornithine-Induced Cytostasis is Reversed by Exogenous Polyamines, Not by Thymidine Supplementation
Next Article in Special Issue
Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin
Previous Article in Journal
Salicylic Acid Biosynthesis and Metabolism: A Divergent Pathway for Plants and Bacteria
Previous Article in Special Issue
Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies
Article

Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy

1
Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, China
2
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China
3
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Stephan M. Huber
Biomolecules 2021, 11(5), 706; https://doi.org/10.3390/biom11050706
Received: 14 March 2021 / Revised: 3 May 2021 / Accepted: 7 May 2021 / Published: 10 May 2021
(This article belongs to the Special Issue Repurposing Drugs for Anti-Cancer Therapy)
Strategies boosting both innate and adaptive immunity have great application prospects in cancer immunotherapy. Antibodies dual blocking the innate checkpoint CD47 and adaptive checkpoint PD-L1 or TIGIT could achieve durable anti-tumor effects. However, a small molecule dual blockade of CD47/SIRPα and TIGIT/PVR pathways has not been investigated. Here, an elevated expression of CD47 and PVR was observed in tumor tissues and cell lines analyzed with the GEO datasets and by flow cytometry, respectively. Compounds approved by the FDA were screened with the software MOE by docking to the potential binding pockets of SIRPα and PVR identified with the corresponding structural analysis. The candidate compounds were screened by blocking and MST binding assays. Azelnidipine was found to dual block CD47/SIRPα and TIGIT/PVR pathways by co-targeting SIRPα and PVR. In vitro, azelnidipine could enhance the macrophage phagocytosis when co-cultured with tumor cells. In vivo, azelnidipine alone or combined with irradiation could significantly inhibit the growth of MC38 tumors. Azelnidipine also significantly inhibits the growth of CT26 tumors, by enhancing the infiltration and function of CD8+ T cell in tumor and systematic immune response in the tumor-draining lymph node and spleen in a CD8+ T cell dependent manner. Our research suggests that the anti-hypertensive drug azelnidipine could be repositioned for cancer immunotherapy. View Full-Text
Keywords: CD47/SIRPα; TIGIT/PVR; drug-repositioning; small molecule inhibitor; azelnidipine; cancer immunotherapy CD47/SIRPα; TIGIT/PVR; drug-repositioning; small molecule inhibitor; azelnidipine; cancer immunotherapy
Show Figures

Figure 1

MDPI and ACS Style

Zhou, X.; Jiao, L.; Qian, Y.; Dong, Q.; Sun, Y.; Zheng, W.V.; Zhao, W.; Zhai, W.; Qiu, L.; Wu, Y.; Wang, H.; Gao, Y.; Chen, J. Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy. Biomolecules 2021, 11, 706. https://doi.org/10.3390/biom11050706

AMA Style

Zhou X, Jiao L, Qian Y, Dong Q, Sun Y, Zheng WV, Zhao W, Zhai W, Qiu L, Wu Y, Wang H, Gao Y, Chen J. Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy. Biomolecules. 2021; 11(5):706. https://doi.org/10.3390/biom11050706

Chicago/Turabian Style

Zhou, Xiuman, Ling Jiao, Yuzhen Qian, Qingyu Dong, Yixuan Sun, Wei V. Zheng, Wenshan Zhao, Wenjie Zhai, Lu Qiu, Yahong Wu, Hongfei Wang, Yanfeng Gao, and Junhui Chen. 2021. "Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy" Biomolecules 11, no. 5: 706. https://doi.org/10.3390/biom11050706

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop