Thursday, November 8, 2012
Figure 1. MuSIC strategy. Multiplex screening for interacting compounds (MuSIC)
technology is able to identify synergistic drug pairs. The technology involves
distributing 1,000 approved or clinically tested drugs [a] into an
arrayed compound library. An algorithm [b]
ensures each of the possible 500,000 interactions between two given molecules
is represented in 13,106 pools [c]. The pools in the primary arrayed
compound library are evaluated for activity against HIV-infected cells [d].
Hits (red wells) from the primary screen are evaluated, and identified
synergistic pairs are used to construct a secondary arrayed compound library,
which also is evaluated for antiviral activity [e]. Hits (red wells)
from the secondary library are validated using concentration titrations of the
two drugs [f]. The analyses of antiviral efficacy for steps [d]
and [e] involved a two-part cell-based assay that measured effects of
molecules on early and later stages of the virus' lifecycle.