Engelhardt Harald, Smits Rogier A, Leurs Rob, Haaksma Eric, de Esch Iwan J P
Boehringer Ingelheim RCV GmbH & Co KG, Department of Medicinal Chemistry, Vienna, Austria.
Curr Opin Drug Discov Devel. 2009 Sep;12(5):628-43.
At the turn of the millennium, the DNA sequence encoding the histamine H4 receptor (H4R) was identified in data from human genome databases. Considering the clinical importance of H1R and H2R ligands, and the clinical trials that are ongoing for H3R ligands, the latest addition to the histamine receptor family was noted with interest by the pharmaceutical industry. Initial studies describing the expression of the H4R, and the activity of this receptor in (patho)physiology, suggested that the H4R played a role in the immune system. The introduction of the reference H4R antagonist JNJ-7777120 (Johnson & Johnson Pharmaceutical Research & Development LLC/Abbott Laboratories), and proof of the efficacy of this agent in models of asthma, allergic rhinitis and pruritus, highlighted the H4R as a novel drug target. The first clinical candidates targeting the H4R have been identified, and new H4R antagonists are expected to enter the clinic in the near future.
在千年之交，人类基因组数据库的数据中鉴定出了编码组胺H4受体（H4R）的DNA序列。鉴于H1R和H2R配体的临床重要性，以及H3R配体正在进行的临床试验，制药行业对组胺受体家族的最新成员予以了关注。最初关于H4R表达及其在（病理）生理学中活性的研究表明，H4R在免疫系统中发挥作用。参考H4R拮抗剂JNJ-7777120（强生制药研发有限责任公司/雅培实验室）的推出，以及该药物在哮喘、过敏性鼻炎和瘙痒模型中的疗效证明，凸显了H4R作为一种新型药物靶点的地位。已确定了首个靶向H4R的临床候选药物，预计新型H4R拮抗剂将在不久的将来进入临床应用。
