作者: Todd M. Covey , Santosh Putta , Alessandra Cesano
关键词:
摘要: Abstract Measuring target coverage of small molecule inhibitors is paramount–first, for selection molecules to progress through the drug development process and second, once a candidate moves clinical testing, guiding dose/schedule selection. Single cell network profiling (SCNP) using multiparameter flow cytometry can measure compound effects on multiple signaling cascades in cell-type-specific manner. We applied SCNP panel compounds with reported inhibitory Jak/Stat novel system where modulation are simultaneously measured discrete subsets whole (ie, unfractionated) blood. Jak2 vs. Jak3 selectivity as well “off-target” other pathways were combination cytokines that different white blood subsets, namely GM-CSF (monocytes/granulocytes), IL-2 (T cells), CD40L (B cells). The then rank-ordered by potency against diff...