CDC7 kinase inhibitors and uses thereof
The invention provides compounds, methods, pharmaceutical compositions, and kits for the treatment of proliferative disorders such as cancer. In one aspect, the methods comprise compounds that inhibit the activity of protein kinases, such as cell division cycle (Cdc) kinase. In another aspect, the methods comprise compounds that inhibit Cdc7 and/or Dbf4 activity. In another aspect, the methods comprise compounds that exhibit anti-proliferative properties useful in treating diseases such as cancer. Compounds useful for any of the methods include compounds of the Formula (A) or (B): or pharmaceutically acceptable salts thereof. Exemplary compounds of Formula (A) or (B) include granaticin A, granaticin B, dihydrogranaticin A, dihydrogranaticin B, medermycin, and actinorhodin.
1. A method for treating pancreatic cancer in a human subject in need thereof, comprising administering to the human subject a therapeutically effective amount of a compound of Formula (II):
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the pancreatic cancer comprises a genetic mutation.
3. The method of claim 2 , wherein the genetic mutation comprises an EGFR mutation, a KRAS mutation, a p53 mutation, a BRAF mutation, a cyclin D mutation, or a chromosomal abnormality.
4. The method of claim 1 , wherein the pancreatic cancer is a multi-drug resistant (MDR) cancer.
5. The method of claim 1 , wherein the pancreatic cancer is relapsed and/or refractory cancer.
6. The method of claim 1 , further comprising administering at least one other therapy or therapeutic agent.
7. The method of claim 6 , further comprising administering radiation.
8. The method of claim 1 , wherein the compound is administered by systemic intravenous injection in a bolus or continuous infusion regimen.