CXCR4 Platform

CXCR4, or C-X-C receptor type 4, is the receptor for the chemokine CXCL12 (also known as stromal derived factor-1, or SDF-1). The CXCR4/CXCL12 pathway has been shown to play an essential role in the normal trafficking of key immune cells to direct immune surveillance throughout the body. Aberrant ligand-receptor signaling causes immune suppression, blocking normal immune function.

  • In certain rare primary immunodeficiency diseases, genetic mutations in the CXCR4 gene result in over-active signaling, causing severely abnormal immune function.
  • In certain rare lymphomas, the somatic mutations in CXCR4 and/or over-expression of CXCL12 play key roles in cancer cell survival signaling within the bone marrow niche, contributing to the resistance of lymphoma cells to standard treatments.
  • In cancer, CXCL12 is over-produced in the tumor microenvironment which promotes multiple mechanisms including resistance, tumor growth, progression and reduced immune surveillance.

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The X4 team has combined its drug development expertise, as well as its insights into CXCR4 biology, to establish a proprietary platform for the discovery and advancement of best-in-class CXCR4 inhibitors. Our platform includes:

  • Intellectual property that includes a portfolio of issued patents and pending applications related to a family of small molecules that antagonize CXCR4
  • Fundamental knowledge of CXCR4 structure and function to identify molecules that demonstrate an allosteric mechanism of inhibition that may result in a prolonged biological effect
  • Deep understanding of the clinical applications of CXCR4 inhibition within multi-drug cancer treatment regimens


CXCR4 is a chemokine receptor belonging to the large superfamily of G protein-coupled receptors. It is directly involved in a number of biological processes including hematopoetic stem cell regulation and immune response. CXCR4 was initially studied in the context of the HIV infection of immune cells, leading to immune deficiency. Its role in hematopoetic stem cell regulation has been exploited in the development of plerixafor, a short-term use, injectable CXCR4 inhibitor approved by the FDA for stem cell mobilization. CXCR4 has been implicated in many cancers and certain rare primary immunodeficiency diseases.