Name:	PF-04494700
Other Names:	TTP488
Therapeutic Applications:	Mild to moderate Alzheimer disease
Therapy Types:	Oral small molecule
Mechanisms:	Inhibitor of Receptor for Advanced Glycation Endproducts (RAGE)
Development Status:	investigational in U.S.
FDA Phase:	Discontinued
Primary Medical Role:	PF-04494700 inhibits the activation of RAGE, a member of the immunoglobulin superfamily, a multi-ligand, cell surface receptor expressed by neurons, microglia, astrocytes and cerebral endothelial cells.
Role in Alzheimer's Disease:	RAGE plays multiple roles in the pathogenesis of AD. RAGE mediates the effects of Aβ on microglia, blood-brain barrier (BBB) and neurons through activating different signaling pathways. The adverse consequences of RAGE interaction with Aβ include disruption of neuronal properties and functions, amplification of glial inflammatory responses, elevation of oxidative stress and amyloidosis, increased Aβ influx at the blood brain barrier and vascular dysfunction, and induction of autoantibodies. Data from autopsy brain tissues, in vitro cell cultures and transgenic mouse models suggest that Aβ-RAGE interaction exaggerates neuronal stress, accumulation of Aβ, impaired learning and memory, and neuroinflammation. Inhibition of RAGE protects against Aβ-mediated cellular disruption.
Companies:	Pfizer, Inc.
Notes:	In December 2007 Pfizer initiated a Phase II clinical study in mild to moderate AD (see ARF related news story.) In November 2011 Pfizer discontinued the development of PF-04494700 (see ARF related news story.) For clinical trials of PF-04494700 on clinicaltrials.gov see PF-04494700 trials. Last updated November 10, 2011