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Fig 1.

The approval timeline of FDA approved multi-target drugs and combination products against the human kinome.

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Fig 2.

A framework of proposed comparative strategy used in this study.

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Fig 3.

Targets of approved multi-target drugs and combination products in the phylogenetic tree of the human kinome adapted from Manning and colleagues [7].

The targets of both multi-target drugs and combination products were highlighted by green circle, while the targets of either multi-target drugs or combination products were highlighted by blue and orange circle respectively.

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Fig 3 Expand

Fig 4.

The drug-target interaction network of the FDA approved multi-target drugs.

Drugs were represented by orange hexagon, and targets were shown by blue ellipse. Drug-target interactions were displayed by edges with shapes of arrow for activation and “T” for inhibition.

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Fig 5.

The drug-target interaction network of the FDA approved combination products.

Small molecular drugs in a specific combination product were represented by round rectangle in orange, and monoclonal antibodies were shown by round rectangle in magenta. The combination products were shown by round rectangles connected by sine-wave, and targets were shown by blue ellipse. Drug-target interactions were displayed by edges with shapes of arrow for activation and “T” for inhibition.

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Fig 6.

Phylogenetic tree representing the homology distance among all targets targeted by approved multi-target drugs and combination products.

The connections shown in the center represented the target pairs aimed by the multi-target drugs (lines in blue) and the combination products (lines in orange). Bars at the end of each connecting line defined the number of multi-target drugs (blue bar) and combination products (orange bar).

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Fig 6 Expand