Collaborations in Chemistry, 601 Runnymede Avenue, Jenkintown, Pennsylvania 19046, USA.
Pharm Res. 2011 Aug;28(8):1785-91. doi: 10.1007/s11095-011-0486-6. Epub 2011 May 24.
From research published in the last six years we have identified 34 studies that have screened libraries of FDA-approved drugs against various whole cell or target assays. These studies have each identified one or more compounds with a suggested new bioactivity that had not been described previously. We now show that 13 of these drugs were active against more than one additional disease, thereby suggesting a degree of promiscuity. We also show that following compilation of all the studies, 109 molecules were identified by screening in vitro. These molecules appear to be statistically more hydrophobic with a higher molecular weight and AlogP than orphan-designated products with at least one marketing approval for a common disease indication or one marketing approval for a rare disease from the FDA's rare disease research database. Capturing these in vitro data on old drugs for new uses will be important for potential reuse and analysis by others to repurpose or reposition these or other existing drugs. We have created databases which can be searched by the public and envisage that these can be updated as more studies are published.
从过去六年发表的研究中,我们确定了 34 项研究,这些研究针对各种全细胞或靶标测定筛选了 FDA 批准药物的文库。这些研究都鉴定出一种或多种以前未描述过的具有新生物活性的化合物。我们现在表明,其中 13 种药物对超过一种额外的疾病有效,这表明具有一定的混杂性。我们还表明,在对所有研究进行汇编后,通过体外筛选鉴定出 109 种分子。这些分子在体外似乎比孤儿药设计产品更具疏水性,分子量和 AlogP 更高,孤儿药是指至少有一种针对常见疾病适应症的市场批准,或至少有一种来自 FDA 罕见疾病研究数据库的罕见疾病适应症的市场批准。对于旧药物的新用途,获取这些体外数据将对其他人重新利用或调整这些或其他现有药物的潜在再利用和分析非常重要。我们已经创建了可以公开搜索的数据库,并设想随着更多研究的发表,这些数据库可以进行更新。