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The more recent development of allosteric inhibitors targeting conformational plasticity of protein kinases offers promising perspectives for therapeutics.  In particular tampering with T\u2010loop dynamics of CDK2 kinase would provide a selective means of inhibiting this kinase, by preventing its conformational activation. To this aim we engineered a fluorescent biosensor that specifically reports on conformational changes of CDK2 activation loop and is insensitive to ATP or ATP\u2010competitive inhibitors, which constitutes a highly sensitive probe for identification of selective T\u2010loop modulators. This biosensor was successfully applied to screen a library of small chemical compounds leading to discovery of a family of quinacridine analogs, which potently inhibit cancer cell proliferation, and promote accumulation of cells in S phase and G2. These compounds bind CDK2\/ Cyclin A, inhibit its kinase activity, compete with substrate binding, but not with ATP, and dock onto the T\u2010loop of CDK2. The best compound also binds CDK4 and CDK4\/Cyclin D1, but not CDK1. The strategy we describe opens new doors for the discovery of a new class of allosteric CDK inhibitors for cancer therapeutics.<\/jats:p>","DOI":"10.1002\/biot.201600531","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T10:39:14Z","timestamp":1492771154000},"source":"Crossref","is-referenced-by-count":19,"title":["Targeting Conformational Activation of CDK2 Kinase"],"prefix":"10.1002","volume":"12","author":[{"given":"Morgan","family":"Pellerano","sequence":"first","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron Universit\u00e9 de Montpellier Facult\u00e9 de Pharmacie  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Tcherniuk","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron Universit\u00e9 de Montpellier Facult\u00e9 de Pharmacie  Montpellier 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