Novel Phenotypic Outcomes Identified for a Public Collection of Approved Drugs from a Publicly Accessible Panel of Assays.
Novel Phenotypic Outcomes Identified for a Public Collection of Approved Drugs from a Publicly Accessible Panel of Assays.
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DOI：
10.1371/journal.pone.0130796
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Thomas CJ
中科院分区：
文献类型：
--
作者：
Lee JA;Shinn P;Jaken S;Oliver S;Willard FS;Heidler S;Peery RB;Oler J;Chu S;Southall N;Dexheimer TS;Smallwood J;Huang R;Guha R;Jadhav A;Cox K;Austin CP;Simeonov A;Sittampalam GS;Husain S;Franklin N;Wild DJ;Yang JJ;Sutherland JJ;Thomas CJ
Phenotypic assays have a proven track record for generating leads that become first-in-class therapies. Whole cell assays that inform on a phenotype or mechanism also possess great potential in drug repositioning studies by illuminating new activities for the existing pharmacopeia. The National Center for Advancing Translational Sciences (NCATS) pharmaceutical collection (NPC) is the largest reported collection of approved small molecule therapeutics that is available for screening in a high-throughput setting. Via a wide-ranging collaborative effort, this library was analyzed in the Open Innovation Drug Discovery (OIDD) phenotypic assay modules publicly offered by Lilly. The results of these tests are publically available online at www.ncats.nih.gov/expertise/preclinical/pd2 and via the PubChem Database (https://pubchem.ncbi.nlm.nih.gov/) (AID 1117321). Phenotypic outcomes for numerous drugs were confirmed, including sulfonylureas as insulin secretagogues and the anti-angiogenesis actions of multikinase inhibitors sorafenib, axitinib and pazopanib. Several novel outcomes were also noted including the Wnt potentiating activities of rotenone and the antifolate class of drugs, and the anti-angiogenic activity of cetaben.
