Pharmacological manipulation of transcription factor protein-protein interactions: opportunities and obstacles

Cell Regeneration

Table 1 Summary of direct TF inhibition strategies

Mode of action	Class of drug	General benefits	General drawbacks	Examples/indication
Inhibition of TF gene expression	Antisense mRNA, siRNA	Selectivity	Antisense mRNA and duplex unstable, poor cellular uptake, pro-inflammatory, resistance mechanisms (gene over-expression)	K-Ras/cancer [67,68]
Binding to TF DNA-binding domain	Decoy oligonucleotide	Selectivity	Low bioavailability, short half-life, poor cellular uptake	Sp1, AP-1, STAT3, Ets-1/cancer [69]
	Small molecule	Bioavailability	Off-target effects	Human androgen receptor/cancer [70]
	Small peptides and peptidomimetics	Less or no side effect	Low bioavailability, unstable, pro-inflammatory	STAT3/cancer [71]
Disruption of protein-protein interaction	Small molecule	Bioavailability	Off-target effects	cMyc/Max, Max/Max, HDM2/p53, Bcl/Bax/cancer [17,60,72,73]
Disruption of protein-protein interaction	Small peptides and peptidomimetics	Less or no side effect	Low bioavailability, unstable, pro-inflammatory	STAT3, MDMX/p53/cancer [74-76]