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. Author manuscript; available in PMC: 2015 Mar 1.
Published in final edited form as: Future Oncol. 2014 May;10(7):1215–1237. doi: 10.2217/fon.14.60

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.