Targeting CXCR1/2: The medicinal potential as cancer immunotherapy agents, antagonists research highlights and challenges ahead

Eur J Med Chem. 2020 Jan 1:185:111853. doi: 10.1016/j.ejmech.2019.111853.

Jinxin Che ¹, Rui Song ², Binhui Chen ³, Xiaowu Dong ⁴

Affiliations

1 ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
2 Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
3 ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address: achenbinhui@hotmail.com.
4 ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address: dongxw@zju.edu.cn.

PMID: 31732253 DOI: 10.1016/j.ejmech.2019.111853

Abstract

Immune suppression in the tumor microenvironment (TME) is an intractable issue in anti-cancer immunotherapy. The chemokine receptors CXCR1 and CXCR2 recruit immune suppressive cells such as the myeloid derived suppressor cells (MDSCs) to the TME. Therefore, CXCR1/2 antagonists have aroused pharmaceutical interest in recent years. In this review, the medicinal chemistry of CXCR1/2 antagonists and their relevance in Cancer Immunotherapy have been summarized. The development of the drug candidates, along with their design rationale, clinical status and current challenges have also been discussed.

Keywords

CXCR1/2 antagonists; Cancer; Classifications; Clinical development; Immunotherapy.

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