DNA2 inhibitors for cancer treatment
Disclosed herein, inter alia, are compositions and methods for inhibiting DNA2.
1. A method of
(i) sensitizing cancer cells to radiation therapy or chemotherapy;
(ii) potentiating clinical efficacy of a PARP inhibitor or a topoisomerase inhibitor;
(iii) inhibiting DNA replication;
(iv) suppressing DNA double-strand break repair end resection, recombination, or over-resection of nascent DNA in cells defective in fork protection, and restart of stalled DNA replication forks in cells; or
(v) interfering with telomere replication or repair; wherein
the method comprising administering a compound or pharmaceutically acceptable salt thereof, wherein the compound is:
or a tautomer of any of the foregoing.
2. The method of claim 1 , wherein the topoisomerase inhibitor is a topoisomerase I inhibitor.
3. The method of claim 1 , further comprising administering a chemotherapeutic agent, radiation, or a combination thereof.
4. A method of treating Fanconi anemia in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof, wherein the compound is:
or a tautomer of any of the foregoing.
5. The method of claim 1 , wherein the method is sensitizing cancer cells to radiation therapy or chemotherapy.
6. The method of claim 5 , further comprising administering a chemotherapeutic agent, radiation, or a combination thereof.
7. The method of claim 1 , wherein the method is inhibiting DNA replication.
8. The method of claim 7 , further comprising further comprising administering a chemotherapeutic agent, radiation, or a combination thereof.