A technique to map covalent targets throughout the entire mammalian body
As single-cell and high spatial resolutions technologies gain momentum, there was a need to develop drug development techniques that help us understand interaction between drugs and their targets at the single cell level.
The researchers leveraged the unique kinetics of click reactions and developed volumetric clearing-assisted tissue click chemistry (vCATCH) enabling cellular-resolution mapping of covalent drug targets throughout three-dimensional (3D) mammalian body.
The authors also combined vCATCH with hydrogel-based reinforcement of three-dimensional imaging solvent-cleared organs (HYBRiD) imaging and virtual reality to visualize and quantify in vivo targets of two clinical cancer drugs, afatinib and ibrutinib. The authors found these cancer drugs known pharmacological distribution and revealed previously unreported tissue and cell-type engagement potentially linked to off-target effects.
