Ward Stephen, Sotsios Yannis, Dowden James, Bruce Ian, Finan Peter
Department of Pharmacy and Pharmacology, Bath University, Claverton Down, Bath, BA2 7AY, United Kingdom.
Chem Biol. 2003 Mar;10(3):207-13. doi: 10.1016/s1074-5521(03)00048-6.
At least one Holy Grail for many academic researchers and pharmaceutical research divisions alike has been to identify therapeutically useful selective PI3K inhibitors. There are several different but closely related PI3Ks which are thought to have distinct biological roles. Until now, however, researchers have been frustrated by poor selectivity of the available pharmacological inhibitors, which are unable to distinguish the different isoforms of PI3K adequately. Fortunately, recently published work gives cause for optimism; there are now several patent specifications published that describe new PI3K inhibitors, including some that are more selective for the delta isoform of PI3K. Given the involvement of PI3Ks in a plethora of biological settings, such isoform-selective inhibitors may have immense potential use for the treatment of patients with inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases.
对于许多学术研究人员和制药研究部门来说，至少有一个圣杯就是找到具有治疗作用的选择性PI3K抑制剂。有几种不同但密切相关的PI3K，它们被认为具有不同的生物学作用。然而，到目前为止，研究人员一直因现有药理抑制剂的选择性差而感到沮丧，这些抑制剂无法充分区分PI3K的不同亚型。幸运的是，最近发表的研究成果令人感到乐观；现在已经有几项专利说明书公布，描述了新的PI3K抑制剂，包括一些对PI3Kδ亚型更具选择性的抑制剂。鉴于PI3K参与了大量生物学过程，这种亚型选择性抑制剂在治疗炎症和自身免疫性疾病以及癌症和心血管疾病患者方面可能具有巨大的潜在用途。
