The diversity of chemical structures that have been reported  to be inhibitors of VCAM-1 expression suggests that there may be numerous upstream molecular targets regulating VCAM-1 expression with which different inhibitors interact. Antioxidants may interact with one target and chalcones with another. Even the antioxidants that have shown inhibition on VCAM-1 expression may interact with different targets of the VCAM-1 expression pathway, since PDTC, AGI-1067, and carvedilol  are different structurally. Therefore, VCAM-1 expression is not a single target in the traditional drug discovery sense. Rather, it is a collective marker of potentially many different upstream molecular targets.
VLA-4, the counter receptor of VCAM-1, is a single target, which has been pursued extensively for drug discovery [100,101]. An antibody of VLA-4, natal-izumab, has shown beneficial effects in treating patients with MS and Crohn's disease [102,103]. The clinical trial with BIO 1211, a small molecule VLA-4 antagonist, was discontinued due to lack of efficacy for asthma . This may mean that VLA-4 is not a viable target for asthma.
The most advanced inhibitor of VCAM-1 expression (AGI-1067) is currently in phase III clinical trials. Since there is no single, unique molecular target for VCAM-1 expression and inhibitors of VCAM-1 expression tend to be multifunctional, it will be challenging to unambiguously assess the outcomes of all inhibitors of VCAM-1 expression.
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