Department of Chemistry , Yale University , New Haven , Connecticut 06520-8107 , United States.
J Med Chem. 2018 Sep 27;61(18):8104-8119. doi: 10.1021/acs.jmedchem.8b00589. Epub 2018 Jun 4.
Macrophage migration inhibitory factor (MIF) is an upstream regulator of the immune response whose dysregulation is tied to a broad spectrum of inflammatory and proliferative disorders. As its complex signaling pathways and pleiotropic nature have been elucidated, it has become an attractive target for drug discovery. Remarkably, MIF is both a cytokine and an enzyme that functions as a keto-enol tautomerase. Strategies including in silico modeling, virtual screening, high-throughput screening, and screening of anti-inflammatory natural products have led to a large and diverse catalogue of MIF inhibitors as well as some understanding of the structure-activity relationships for compounds binding MIF's tautomerase active site. With possible clinical trials of some MIF inhibitors on the horizon, it is an opportune time to review the literature to seek trends, address inconsistencies, and identify promising new avenues of research.
巨噬细胞移动抑制因子（MIF）是免疫反应的上游调节剂，其失调与广泛的炎症和增殖性疾病有关。随着其复杂的信号通路和多效性的阐明，它已成为药物发现的有吸引力的靶点。值得注意的是，MIF 既是细胞因子又是酶，作为酮-烯醇互变异构酶发挥作用。包括计算机建模、虚拟筛选、高通量筛选和抗炎天然产物筛选在内的策略，已经产生了大量多样化的 MIF 抑制剂，并对结合 MIF 互变异构酶活性位点的化合物的结构-活性关系有了一定的了解。随着一些 MIF 抑制剂的临床试验即将到来，现在正是回顾文献以寻求趋势、解决不一致性并确定有前途的新研究途径的好时机。
