Ghoreschi Kamran, Laurence Arian, O'Shea John J
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Nat Immunol. 2009 Apr;10(4):356-60. doi: 10.1038/ni.1701. Epub 2009 Mar 19.
Protein kinases, which serve critical functions in signaling pathways in all cells, are popular therapeutic targets. At present, eight kinase inhibitors have been approved in the United States, each of which shows nanomolar potency. Although the initial goal was to generate inhibitors with a high degree of selectivity, recent experience has revealed that many of these approved compounds target more than one kinase. Surprisingly, this promiscuity is less problematic than one would have imagined; indeed, it opens new therapeutic opportunities. In this Perspective, we discuss the present status of Janus kinase inhibitors-a new class of immunosuppressive drugs-and the advantages and disadvantages of selectively inhibiting this class of kinase.
蛋白激酶在所有细胞的信号通路中发挥关键作用，是热门的治疗靶点。目前，美国已批准了8种激酶抑制剂，每种都具有纳摩尔级别的效力。尽管最初的目标是开发具有高度选择性的抑制剂，但最近的经验表明，这些已获批的化合物中有许多靶向不止一种激酶。令人惊讶的是，这种多靶点作用带来的问题比想象的要少；事实上，它开辟了新的治疗机会。在这篇观点文章中，我们讨论了一类新型免疫抑制药物——Janus激酶抑制剂的现状，以及选择性抑制这类激酶的优缺点。
