Investigation of binding proteins for anti-platelet agent K-134 by Drug-Western method |
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Authors: | Ikenoya Mami Doi Takeshi Miura Toru Sawanobori Kimio Nishio Masahiro Hidaka Hiroyoshi |
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Institution: | Tokyo New Drug Research Laboratories I, Kowa Company, Ltd., Noguchi-cho, Higashimurayama, Tokyo 189-0022, Japan. |
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Abstract: | K-134 ((-)-6-3-3-cyclopropyl-3-(1R, 2R)-2-hydroxycyclohexyl]ureido]-propoxy]-2(1H)-quinolinone) is a novel anti-platelet agent with anti-hyperplastic activities. We found previously that K-134 is a potent phosphodiesterase-3 (PDE3) inhibitor. In the present study, we found other K-134-binding proteins by Drug-Western method. We isolated two clones that can bind directly to K-134, cofilin-2, and CD36 in vitro. Comparison of their amino acid sequences showed similarity over a short stretch KxxxxVxIxWxxE] in part in the collagen-binding region of CD36. K-134 inhibited binding between CD36 and collagen type-I; however, other PDE3 inhibitors, cilostazol, amrinone, and an inactive derivative of K-134, 4S-OH-K-134, showed little or no effect on binding. It was strongly suggested that the direct binding between K-134 and CD36 is a characteristic effect of K-134, and the homologous stretch may be necessary for binding to K-134. These results also suggested that these interactions are involved in the mechanisms of the anti-platelet and anti-hyperplastic effects of K-134. |
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Keywords: | K-134 Cofilin-2 CD36 GPIV Anti-platelet agent Anti-hyperplastic effects Phosphodiesterase-3 Cilostazol |
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