| Literature DB >> 23164706 |
Long Ye1, Tiffany Dickerson, Handeep Kaur, Yoko K Takada, Masaaki Fujita, Ruiwu Liu, John M Knapp, Kit S Lam, Neil E Schore, Mark J Kurth, Yoshikazu Takada.
Abstract
Increased concentrations of secreted phospholipase A2 type IIA (sPLA2-IIA), have been found in the synovial fluid of patients with rheumatoid arthritis. It has been shown that sPLA2-IIA specifically binds to integrin αvβ3, and initiates a signaling pathway that leads to cell proliferation and inflammation. Therefore, the interaction between integrin and sPLA2-IIA could be a potential therapeutic target for the treatment of proliferation or inflammation-related diseases. Two one-bead-one-compound peptide libraries were constructed and screened, and seven target hits were identified. Herein we report the identification, synthesis, and biological testing of two pyrazolylthiazole-tethered peptide hits and their analogs. Biological assays showed that these compounds were able to suppress the sPLA2-IIA-integrin interaction and sPLA2-IIA-induced migration of monocytic cells and that the blockade of the sPLA2-IIA-integrin binding was specific to sPLA2-IIA and not to the integrin.Entities:
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Year: 2012 PMID： 23164706 PMCID： PMC4570851 DOI： 10.1016/j.bmcl.2012.10.080
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823