Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies

Table 1 Comparison among PROTACs, small molecule inhibitors (SMIs), monoclonal antibodies, and therapeutic nucleic acids (TNAs)

PROTACs	SMIs	Monoclonal antibodies	TNAs
Highly selective	Poor selectivity	Selective	Selective
Oral bioavailability can be achieved	Oral bioavailability is easy to achieve	Oral bioavailability is not achievable	Oral bioavailability is not achievable
Can target proteins on cell surface and inside a cell	Can target proteins on cell surface and inside a cell	Can only target proteins on cell surface, not inside a cell	Target DNA or RNA
Tissue penetration is good	Tissue penetration is good	Tissue penetration is poor	Tissue penetration is poor
Metabolic stability is good	Metabolic stability is good	Metabolic stability is poor	Metabolic stability is poor
Sub-stoichiometric concentrations are required	Stoichiometric concentrations are required	N/A	N/A
Can target proteins without an active binding site i.e. undruggable proteins	Difficult to target proteins without an active binding site	N/A	N/A
Can target mutated proteins	Cannot target mutated proteins	N/A	N/A
Degradation blocks both enzymatic and scaffolding functions	Inhibition blocks only enzymatic functions	N/A	N/A

ISSN: 1756-8722