Abstract：
Gemfibrozil (GEM) is an orally administered lipid-regulating fibrate derivative drug sold under the brand name Lopid®, among others. Since its approval in the early 80s, GEM has been largely applied to treat hypertriglyceridemia and other disorders of lipid metabolism. Though generally well tolerated, GEM can alter the distribution and the free, active concentration of some co-administered drugs, leading to adverse effects. Most of them appear to be related to the ability of GEM to bind with high affinity human serum albumin (HSA), the major drug-carrier protein in blood plasma. Here, we report the crystal structure of HSA in complex with GEM. Two binding sites have been identified, namely Sudlow\'s binding sites I (FA7) and II (FA3-FA4). A comparison of the crystal structure of HSA in complex with GEM with those of other previously described HSA-drug complexes enabled us to appreciate the analogies and differences in their respective binding modes. The elucidation of the molecular interaction between GEM and HSA might offer the basis for the development of novel GEM derivatives that can be safely and synergistically co-administered with other drugs, enabling augmented therapeutic efficacies.
摘要：
吉非贝齐（GEM）是一种口服给药的调脂贝特衍生物药物，以Lopid®品牌出售，在其他人中。自80年代初批准以来，GEM已大量用于治疗高甘油三酯血症和其他脂质代谢紊乱。虽然一般耐受性良好，创业板可以改变分配和自由，一些共同给药的药物的活性浓度，导致不良影响。它们中的大多数似乎与GEM与高亲和力人血清白蛋白（HSA）结合的能力有关，血浆中主要的药物载体蛋白。这里,我们报道了HSA与GEM配合物的晶体结构。已经确定了两个结合位点，即Sudlow\'s结合位点I(FA7)和II(FA3-FA4)。将GEM复合物中HSA的晶体结构与其他先前描述的HSA-药物复合物的晶体结构进行比较，使我们能够了解它们各自结合模式的类比和差异。GEM和HSA之间的分子相互作用的阐明可能为开发新的GEM衍生物提供基础，这些衍生物可以与其他药物安全和协同地共同给药。实现增强的治疗效果。
