Dana-farber-cancer Institute Inc.

Yu J Zhang

Barrett J Rollins

The invention relates to a human MCP-1 derivative, and pharmaceutical compositions thereof, wherein human MCP-1 has been modified such that the protein inhibits monocyte chemoattractant activity. Successful inhibition of the activity is found where the MCP-1 is modified in one or more of the following: a) the 28-tyrosine is substituted by aspartate, b) the 24-arginine is substituted by phenylalanine, c) the 3-aspartate is substituted by alanine, and/or d) the 2-8 amino acid sequence is deleted. The claimed MCP-1 derivatives can be administered to a patient in need of inhibiting MCP-1 monocyte chemoattractant activity. For example, the derivatives can be used to prevent restenosis, such as that which is common in a patient undergoing coronary artery angioplasty. The invention further relates to compositions and methods of inhibiting monocyte chemoattractant activity of MCP-1 employing the derivatives described.

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Brookline, MA, United States of America

Yu J Zhang