CXCR4 Antagonists for the Treatment of Cancer


Small molecules containing either the piperidine or piperazine core which act as antagonists to C-X-C chemokine receptor type 4 (CXCR4) and may be orally administered.

Key Benefits

  • Orally administered CXCR4 antagonists with diverse clinical applications in oncology.
  • Mobilize white blood cells in mice in a dose-dependent manner.
  • Cause apoptosis-cell death in CXCR4 expressing breast cancer cells.
  • Non-toxic to normal immune cells (T-cells, macrophages).

Market Summary

The CXCR4 receptor is expressed in more than 20 types of cancers, making it the most prevalent chemokine receptor in the oncology area. This receptor is directly responsible for cancer metastasis in many of these cases and is correlated with lower cancer survival rates. The receptor facilitates tumor angiogenesis by recruitment of endothelial cells to the cancerous tissues and controls cancer immunosuppression by recruiting T-regulatory cells (Tregs) to the tumor area restricting lymphocyte responses. The chemokine receptor CXCR4 is also broadly expressed on most hematopoietic cell types. Hematopoietic stem cell transplantation (HSCT) is a common treatment in patients with hematologic malignancies and nonmalignant hematologic disorders. Successful HSCT depends on the ability to mobilize stem cells from the bone marrow into the blood stream to be collected for therapeutic use.

Technical Summary

The targeted disruption of the CXCR4 receptor assists in the mobilization of stem cells for autologous transplantation therapy in patients with blood cancer. Researchers at Emory University have developed two series of small molecules, containing either a piperidine or piperazine ring structure, which act as antagonists to CXCR4 promoting hematopoietic cell mobilization. This technology can be used for adult stem cell transplantation in cases of non-Hodgkins lymphoma and multiple myeloma, especially in cases where patients have inadequate cell mobilization. Results also indicate this technology can be applied in the treatment of breast cancer and in controlling the spread of many types of cancers through blocking metastasis. Due to the complex nature of CXCR4 involvement in cancer, these molecules may have a wide applicability in various areas of oncology. These compounds may play a role in reducing metastasis, tumor angiogenesis, and resistance to chemotherapy, as well as regulating immune system responses in cancer.

Development Stage

Over 250 compounds have been profiled in multiple assays. Lead compounds identified.


Truax et al. ACS Med Chem Lett. 2013 Nov 14; 4(11): 1025–1030. doi: 10.1021/ml400183q
Zhao et al. Bioorg Med Chem Lett. 2015 Nov 1;25(21):4950-5. doi: 10.1016/j.bmcl.2015.04.036

Patent Information

App Type Country Serial No. Patent No. File Date Issued Date Patent Status
EP Registered Country France 11844404.1 2646430 12/2/2011 9/21/2016 Issued
EP Registered Country Germany 11844404.1 2646430 12/2/2011 9/21/2016 Issued
EP Registered Country Ireland 11844404.1 2646430 12/2/2011 9/21/2016 Issued
EP Registered Country Spain 11844404.1 2646430 12/2/2011 9/21/2016 Issued
EP Registered Country United Kingdom 11844404.1 2646430 12/2/2011 9/21/2016 Issued
Nationalized PCT - United States United States 13/879,809 8,969,381 4/17/2013 3/3/2015 Issued
Nationalized PCT - Foreign Australia 2011336397 2011336397 5/16/2013 3/30/2017 Issued
Nationalized PCT - Foreign EP 11844404.1 2646430 5/21/2013 9/21/2016 Issued
Nationalized PCT - Foreign Canada 2,819,468 2,819,468 5/30/2013 1/29/2019 Issued
Continuation United States 14/623,772 9,545,403 2/17/2015 1/17/2017 Issued
Divisional France 16183063.3 3153510 8/5/2016 5/6/2020 Issued
Divisional Germany 16183063.3 3153510 8/5/2016 5/6/2020 Issued
Divisional United Kingdom 16183063.3 3153510 8/5/2016 5/6/2020 Issued
Divisional EP 16183063.3 3153510 8/5/2016 5/6/2020 Issued
Continuation United States 15/370,611 10,016,408 12/6/2016 7/10/2018 Issued
Tech ID: 11014
Published: 4/27/2017