**Background**
The C-X-C chemokine receptor type 4 (CXCR4) and its ligand, CXCL12, play a critical role in the homing, retention, and mobilization of hematopoietic stem/progenitor cells (HSPCs) within the bone marrow niche. The CXCR4/CXCL12 axis is a primary regulator of the bone marrow microenvironment, and its disruption is essential for the mobilization of stem cells into the peripheral blood. This process is clinically vital for autologous hematopoietic stem cell transplantation (ASCT), particularly in patients with multiple myeloma and lymphoma. By antagonizing this pathway, researchers can enhance the collection of CD34+ cells for therapeutic use. In this context, we will introduce a potent CXCR4 antagonist – Burixafor.
**Definition**
Burixafor (TG-0054) hydrobromide is a potent CXCR4 antagonist and inverse agonist with a pIC50 of 7.4.
**In Vitro and In Vivo Studies**
According to the Burixafor description, this compound inhibits the binding of CXCL12 to CXCR4, antagonizes the recruitment of Gαᵢ and β-arrestin2, and blocks downstream Gαᵢ-mediated inhibitory effects on cAMP signal transduction. In terms of Burixafor in vitro activity, the compound potently displaces CXCL12 from CXCR4 on HEK293 cells stably expressing SNAP-CXCR4 (pIC50 = 7.4). In transiently transfected HEK293 cells, it inhibits CXCL12-induced recruitment of miniGαᵢ (pIC50 = 7.7) and β-arrestin2 (pIC50 = 8.0). Furthermore, it reverses CXCR4-dependent inhibition of cAMP in HEK293 cells (pIC50 = 7.9) and acts as a potent inverse agonist on the constitutively active CXCR4 N119S mutant (pIC50 = 7.5).
Regarding Burixafor in vivo efficacy, the compound has demonstrated the ability to mobilize mesenchymal stem cells, reduce inflammation, and maintain cardiac systolic function in porcine myocardial infarction models. In a Mycophenolate-treated swine heart transplant model, it suppressed cardiac allograft vasculopathy and decreased the incidence of acute rejection. Additionally, Burixafor mobilizes HSPCs in mice, showing enhanced efficacy when co-administered with Propranolol. In conclusion, Burixafor is a potent CXCR4 antagonist that facilitates the mobilization of hematopoietic stem/progenitor cells and holds significant potential for research in ASCT and inflammatory cardiac conditions.
Keywords
Burixafor, 1191450-19-7, TG-0054, TG0054, TG 0054, CXCR, CXC chemokine receptors, C-X-C motif chemokine receptors, Inhibitor, inhibitor, inhibit
References
[1] Pan KS, et al. Pharmacological characterization of a clinical candidate, TG-0054, a small molecule inverse agonist targeting CXCR4. Mol Pharmacol. 2025;107(4):100015.
[2] Sukhtankar DD, et al. Burixafor, a CXCR4 inhibitor with a differentiated kinetics profile: results of a phase 2 study for rapid cell mobilization in multiple myeloma and lymphoma patients undergoing transplant. Ann Hematol. 2026;105(3):86. Published 2026 Feb 4.