Table 4.

Mismatch repair inhibitors in development.

MMR protein	Function(s)	Rationales for inhibiting	Challenges	Compounds being investigated
MLH1	Scaffolding protein Damage sensor Helps determine the specific strand error	Can be hypomethylated to restore functionality Inhibition in deficient cells could theoretically cause a synthetic lethality	MMR deficiencies cause or increase chemoresistance Intact MMR function is crucial for proper cell cycle checkpoint control	To restore functionality:
				• FdCyd
				To create synthetic lethality in MLH1-deficient cells (cell studies):
				• Pol γ inhibitor
MSH2	Damage sensor	Its damage-sensing ability can be bypassed by inducing a synthetic lethality	MMR deficiencies cause or increase chemoresistance Intact MMR function is crucial for proper cell cycle checkpoint control	In clinical trials:
				• Methotrexate
				In MLH2-deficient cells (cell studies):
				• Pol β inhibitor

MMR: Mismatch repair.