CXCR3 antagonists

Berry K. Evaluation of T0906487, a CXCR3 antagonist, in a phase 2a psoriasis trial. Inflammation Res 2004 Suppl 53 ps222. 

Fig. 5. Structures of (A) CP-481,715, (B) BX 471, and (C) T487. CP-481,715 and BX 471 are specific CCR1 antagonists from Pfizer and Berlex/Schering AG, and both failed to exhibit efficacy for rheumatoid arthritis and multiple sclerosis, respectively, in phase II trials. T487 is a specific CXCR3 antagonist from Amgen/Turalik that failed in phase Ha psoriasis clinical trials due to lack of efficacy.

CXCR3 CXCL9, CXCLIO, CXCLll Presence of CXCR3 in human disease CXCR3 antagonist (attenuation of lesion formation) ApoE CXCR3 (less development of disease)... 

Akahori, T. et al. (2006) A novel CCR5/CXCR3 antagonist protects intestinal ischemia/reperflision injury. Transplantation Proceedings, 38 (10), 3366-3368. 

Section 13.4 adds perspective to the experimental results obtained so far with these CXCR3 antagonists in disease models and in dinical trials. As such, it provides a useful overview of how synthetic antagonists have helped umaveling the therapeutic potential of CXCR3. 

Autoimmune Diseases. CXCR3 antagonists may have the potential to counteract unwanted immune responses in autoimmune diseases. Here, three examples are highlighted rheumatoid arthritis, multiple sclerosis and Sjogren s syndrome. 

Atherosclerosis. CXCR3 antagonist NBI-74330 (5) gave rise to reduction in lesion formation in atherosclerosis models by the inhibition of effector cell migration to the plaque and by regulating the local immune response [106]. 

Duquette, J., Du, X., Chan, J., Lemon, B., Collins, T., Tonn, G., Medina, J., and Chen,X. (2007) Pyrido[l,2-a]pyrimidin-4-ones as potent CXCR3 antagonists. Presented at the 234th ACS National Meeting (Boston, MA), Aug 19-23 2007, MEDI381. 

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