Development of low molecular weight CXCR4 antagonists by exploratory structural tuning of cyclic tetra- and pentapeptide-scaffolds towards the treatment of HIV infection, cancer metastasis and rheumatoid arthritis. Export

@article{citeulike:3878385, abstract = {The chemokine receptor, CXCR4, is a GPCR that transduces signals of its endogenous ligand, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 system plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, etc. This system has recently been proven to be involved in several problematic diseases, including HIV infection, cancer cell metastasis, leukemia cell progression, rheumatoid arthritis (RA) and pulmonary fibrosis. Thus, CXCR4 is thought to be an important therapeutic target to overcome the above diseases. Fourteen-mer peptides, T140 and its analogs, were previously found to be specific CXCR4 antagonists that were characterized as HIV-entry inhibitors, anti-cancer-metastatic agents, anti-chronic lymphocytic/acute lymphoblastic leukemia agents and anti-RA agents. Based on our knowledge of pharmacophores of T140, CXCR4 antagonists, such as FC131, were previously found by the efficient utilization of cyclic pentapeptide libraries. This review article focuses on our recent research on the development of low molecular weight CXCR4 antagonists including FC131 analogs, in which structural tuning of the cyclic peptide ring and chemical modifications were performed for an increase in potency and a reduction of the peptide character.}, author = {Tamamura, H. and Tsutsumi, H. and Masuno, H. and Fujii, N.}, citeulike-article-id = {3878385}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/17266570}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=17266570}, issn = {0929-8673}, journal = {Current medicinal chemistry}, keywords = {antagonist, cancer, chemokine, disease, drug}, number = {1}, pages = {93--102}, posted-at = {2009-01-12 15:53:35}, priority = {2}, title = {Development of low molecular weight CXCR4 antagonists by exploratory structural tuning of cyclic tetra- and pentapeptide-scaffolds towards the treatment of HIV infection, cancer metastasis and rheumatoid arthritis.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/17266570}, volume = {14}, year = {2007} }

TY - JOUR ID - citeulike:3878385 L3 - citeulike-article-id:3878385 N2 - The chemokine receptor, CXCR4, is a GPCR that transduces signals of its endogenous ligand, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 system plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, etc. This system has recently been proven to be involved in several problematic diseases, including HIV infection, cancer cell metastasis, leukemia cell progression, rheumatoid arthritis (RA) and pulmonary fibrosis. Thus, CXCR4 is thought to be an important therapeutic target to overcome the above diseases. Fourteen-mer peptides, T140 and its analogs, were previously found to be specific CXCR4 antagonists that were characterized as HIV-entry inhibitors, anti-cancer-metastatic agents, anti-chronic lymphocytic/acute lymphoblastic leukemia agents and anti-RA agents. Based on our knowledge of pharmacophores of T140, CXCR4 antagonists, such as FC131, were previously found by the efficient utilization of cyclic pentapeptide libraries. This review article focuses on our recent research on the development of low molecular weight CXCR4 antagonists including FC131 analogs, in which structural tuning of the cyclic peptide ring and chemical modifications were performed for an increase in potency and a reduction of the peptide character. IS - 1 JF - Current medicinal chemistry SN - 0929-8673 EP - 102 TI - Development of low molecular weight CXCR4 antagonists by exploratory structural tuning of cyclic tetra- and pentapeptide-scaffolds towards the treatment of HIV infection, cancer metastasis and rheumatoid arthritis. VL - 14 SP - 93 KW - antagonist KW - cancer KW - chemokine KW - disease KW - drug AU - Tamamura, H AU - Tsutsumi, H AU - Masuno, H AU - Fujii, N PY - 2007/// UR - http://view.ncbi.nlm.nih.gov/pubmed/17266570 ER -