Small molecule and peptide-based CXCR4 modulators as therapeutic agents. A patent review for the period from 2010 to 2018

Introduction: The chemokine receptor CXCR4 has been under intense study due to the central role it plays in immune system regulation and the pathology of many human diseases. The FDA approval of the first CXCR4 antagonist drug Plerixafor (i.e. AMD3100, Mozobil (R)) ushered in an increase in patent activity covering CXCR4 based therapeutic agents over the past decade. Areas covered: This article describes patent documents published during the period of 2010 through 2018 for both small molecules and peptide-based CXCR4 modulators as therapeutic agents. There is an expansion of intellectual property (IP) around existing and new small molecules of clinical interest, including new chemotypes featuring aromatic and aliphatic heterocycles. There is also significant IP covering peptide-based therapeutics, although about half as many in number as those covering small molecules. Expert opinion: In the last decade there has been significant interest in modulators of the CXCR4 receptor, as gauged by the number of patent filings and clinical investigations targeting this receptor for human disease intervention. Seven of the many CXCR4 modulators described herein, that are currently in human clinical trials, are likely to spur the creation of other FDA approved therapeutics in the near future, most likely as immune and oncology drugs.