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Molecular pharmacology of immunosuppressive agents in relation to their clinical use

Kung, Lina BSc; Gourishankar, Sita MD; Halloran, Philip F. MD, PhD

Current Opinion in Organ Transplantation: September 2000 - Volume 5 - Issue 3 - p 268-275

As the molecular basis of the immune response is elucidated, the opportunities for intervention with agents with established sites of action increase. With conventional small molecular drugs, major sites of action have been identified, such as inhibition of calcineurin, target of rapapmycin, and inosine monophosphate dehydrogenase. However, relating these effects to the actions and toxicities of the drugs remains incomplete. The focus now is on further characterizing these important signaling pathways. The proteins targeting surface molecules such as CD3, CD40L, B7, and others are better understood. The accumulated experience with these interventions furthers our understanding of these agents and the human immune response. The failure of a promising agent in some trials may reveal an incomplete understanding of the targeted biologic process in vivo. Studies with gene knockout mice also help us better understand the roles of these molecules and the molecular basis of how these agents might work. Curr Opin Organ Transplant 2000, 5:268–275 © 2000 Lippincott Williams & Wilkins, Inc.

Department of Medicine, Division of Nephrology & Immunology, University of Alberta, Edmonton, Alberta, Canada

Correspondence to Philip F. Halloran, Department of Medicine, Division of Nephrology & Immunology, University of Alberta, 250 Heritage Medical Research Centre, Edmonton, Alberta T6G 2S2, Canada

© 2000 Lippincott Williams & Wilkins, Inc.