CXCR4 antagonist AMD3100 (plerixafor): From an impurity to a therapeutic agent

Jingzhe Wang; Bakhos A Tannous; Mark C Poznansky; Huabiao Chen

doi:10.1016/j.phrs.2020.105010

CXCR4 antagonist AMD3100 (plerixafor): From an impurity to a therapeutic agent

Pharmacol Res. 2020 Sep:159:105010. doi: 10.1016/j.phrs.2020.105010. Epub 2020 Jun 13.

Authors

Jingzhe Wang¹, Bakhos A Tannous², Mark C Poznansky³, Huabiao Chen⁴

Affiliations

¹ Jiangsu Key Laboratory of Clinical Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.
² Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA; Harvard Medical School, Boston, MA, 02115, USA.
³ Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Harvard Medical School, Boston, MA, 02115, USA.
⁴ Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA; Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Harvard Medical School, Boston, MA, 02115, USA. Electronic address: Huabiao.Chen@mgh.harvard.edu.

PMID: 32544428
DOI: 10.1016/j.phrs.2020.105010

Abstract

AMD3100 (plerixafor), a CXCR4 antagonist, has opened a variety of avenues for potential therapeutic approaches in different refractory diseases. The CXCL12/CXCR4 axis and its signaling pathways are involved in diverse disorders including HIV-1 infection, tumor development, non-Hodgkin lymphoma, multiple myeloma, WHIM Syndrome, and so on. The mechanisms of action of AMD3100 may relate to mobilizing hematopoietic stem cells, blocking infection of X4 HIV-1, increasing circulating neutrophils, lymphocytes and monocytes, reducing myeloid-derived suppressor cells, and enhancing cytotoxic T-cell infiltration in tumors. Here, we first revisit the pharmacological discovery of AMD3100. We then review monotherapy of AMD3100 and combination use of AMD3100 with other agents in various diseases. Among those, we highlight the perspective of AMD3100 as an immunomodulator to regulate immune responses particularly in the tumor microenvironment and synergize with other therapeutics. All the pre-clinical studies support the clinical testing of the monotherapy and combination therapies with AMD3100 and further development for use in humans.

Keywords: AMD3100; CXCR4; Combination therapy; Monotherapy.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Anti-HIV Agents / adverse effects
Anti-HIV Agents / therapeutic use*
Antineoplastic Agents / adverse effects
Antineoplastic Agents / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols
Autoimmune Diseases / drug therapy
Autoimmune Diseases / immunology
Autoimmune Diseases / metabolism
Benzylamines / adverse effects
Benzylamines / therapeutic use*
Cyclams / adverse effects
Cyclams / therapeutic use*
Drug Contamination
HIV Infections / drug therapy*
HIV Infections / immunology
HIV Infections / metabolism
HIV Infections / virology
Humans
Neoplasms / drug therapy*
Neoplasms / immunology
Neoplasms / metabolism
Primary Immunodeficiency Diseases / drug therapy
Primary Immunodeficiency Diseases / immunology
Primary Immunodeficiency Diseases / metabolism
Receptors, CXCR4 / antagonists & inhibitors*
Receptors, CXCR4 / metabolism
Signal Transduction
Tumor Microenvironment
Warts / drug therapy
Warts / immunology
Warts / metabolism

Substances

Anti-HIV Agents
Antineoplastic Agents
Benzylamines
CXCR4 protein, human
Cyclams
Receptors, CXCR4
plerixafor

Supplementary concepts

WHIM syndrome