Maraviroc | CCR5 Antagonist

Maraviroc (376348-65-1) is a potent and selective CCR5 antagonist with potent anti-HIV activity. It prevents HIV-1 gp120 binding to CCR5 preventing cell-cell fusion. Maraviroc inhibited MIP-1a (IC₅₀ = 3.3 nM), MIP-1b (IC₅₀ = 7.2 nM), and RANTES (IC₅₀ = 5.2 nM) binding to CCR5-expressing HEK-293.¹ Clinically useful antiretroviral drug. Many cancer cells express CCR5: Maraviroc blocked metastasis of basal breast² and pancreatic cancer³ cells, induced cytotoxic and apoptotic effects in colorectal cancer cells⁴, reduced metastatic tumor growth in lungs⁵, and suppresses growth in acute ALL cells⁶. CCR5 inhibition with maraviroc induced macrophage repolarization with anti-tumoral effects.⁷

References/Citations:

1) Dorr et al. (2005), Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity; Antimicrob.Agents Chemother. 49 4721
2) Velasco-Velazquez et al. (2012), CCR5 antagonist blocks metastasis of basal breast cancer cells; Cancer Res. 72 3839
3) Singh et al. (2018), CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells; Sci.Rep. 8 1323
4) Pervaiz et al. (2015), CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells; Med.Oncol. 32 158
5) Halvorsen et al. (2016), Maraviroc decreases CCL8-mediated migration of CCR5(+) regulatory T cells and reduces metastatic tumor growth in the lungs; Oncoimmunology 5 e1150398
6) Zi et al. (2017), Treatment with the C-C chemokine receptor type 5(CCR5)-inhibitor maraviroc suppresses growth and induces apoptosis of acute lymphoblastic leukemia cells; Am.J.Cancer Res. 7 869
7) Halama et al. (2016), Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be targeted Effectively by Anti-CCR5 Therapy in Cancer Patients; Cancer Cell 29 587