The therapeutic potential of CXCR4 antagonists in the treatment of HIV infection, cancer metastasis and rheumatoid arthritis.
CXCR4 is the receptor of the chemokine CXCL12, which is involved in progression and metastasis of several types of cancer cells, HIV infection and rheumatoid arthritis. The authors developed selective CXCR4 antagonists, T22 and T140, initially as anti-HIV agents, which inhibit T cell line-tropic (X4-) HIV-1 infection through their specific binding to CXCR4. Recently, T140 analogues have also been shown to inhibit CXCL12-induced migration of breast cancer cells, leukaemia T cells, pancreatic cancer cells, small cell lung cancer cells, chronic lymphocytic leukaemia B cells, pre-B acute lymphoblastic leukaemia cells and so on in vitro. Biostable T140 analogues significantly suppressed pulmonary metastasis of breast cancer cells and melanoma cells in mice. Furthermore, these compounds significantly suppressed the delayed-type hypersensitivity response induced by sheep red blood cells and collagen-induced arthritis, which represent in vivo mouse models of arthritis. Thus, T140 analogues proved to be attractive lead compounds for chemotherapy of these problematic diseases. This article reviews recent research on T140 analogues, referring to several other CXCR4 antagonists.
Tamamura
Hirokazu
H
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan. tamamura.mr@tmd.ac.jp
Fujii
Nobutaka
N
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002464:Cell Migration Inhibition; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000276:immunology / Q000517:prevention & control*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000502:physiology
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D019718:Receptors, CXCR4