The druggable genome and support for target identification and validation in drug development.
The druggable genome and support for target identification and validation in drug development.
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DOI：
10.1126/scitranslmed.aag1166
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发表时间：
2017-03-29
影响因子：
17.1
通讯作者：
Casas JP
中科院分区：
文献类型：
--
作者：
Finan C;Gaulton A;Kruger FA;Lumbers RT;Shah T;Engmann J;Galver L;Kelley R;Karlsson A;Santos R;Overington JP;Hingorani AD;Casas JP
靶标识别（确定疾病的正确药物靶标）和靶标验证（证明靶标扰动对疾病生物标志物和疾病终点的影响）是药物开发的重要步骤。编码药物靶标的基因变异的临床相关关联在药理学上模拟了修改相同靶标的效果。为了描述这种模式带来的药物开发（包括重新利用）机会，我们将来自全基因组关联研究（GWAS）的复杂疾病和生物标志物相关位点与一组更新的编码可药物人类蛋白的基因，与针对这些靶点具有生物活性的药物，以及在有许可药物的情况下，与临床适应症联系起来。我们使用这组基因来设计一个新的基因分型阵列，这将使可药物基因的关联研究能够用于人类疾病的药物靶点选择和验证。
Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end-points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies (GWAS) to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets and, where there were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, which will enable association studies of druggable genes for drug target selection and validation in human disease.
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影响因子：
120.1
作者：
Cook, David;Brown, Dearg;Pangalos, Menelas N.
通讯作者：
Pangalos, Menelas N.
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
17.1
作者：
Collins, Francis S.
通讯作者：
Collins, Francis S.
影响因子：
15.8
作者：
Ioannidis, JPA
通讯作者：
Ioannidis, JPA
影响因子：
3.5
作者：
Colquhoun D
通讯作者：
Colquhoun D