IP Library › Granted Patent US 8,481,557
Granted Patent B2
US 8,481,557 · App. 12/757,954 · Granted Jul 9, 2013

Method of treatment using checkpoint kinase 1 inhibitors

Inventors: Michael J. Humphries (Boulder, CO); Shannon L. Winski (Boulder, CO)
Assignee: Array Biopharma Inc.
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Quick Facts
Patent No.
US 8,481,557
App. No.
12/757,954
Granted
Jul 9, 2013
Kind
B2
Abstract

Methods of treating cancer by administering a DNA damaging agent and a CHK 1 Inhibitor on a dosing regimen are provided.

Claims (28)

1. A method for treating cancer by administering a DNA damaging agent and two doses of a CHK 1 inhibitor selected from (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide and (R)—N-(4-(3-aminopiperidin-1 -yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-y)isobutyramide, (R)—N-(5-bromo-4-(3-(methylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide, (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methylnicotinamide, (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide, (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbutanamide, and (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyclopropylacetamide, wherein the first dose of the CHK1 inhibitor is administered one day after the DNA damaging agent, and the second dose of the CHK1 inhibitor is administered two days after the DNA damaging agent.

2. The method of claim 1 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide.

3. The method of claim 1 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide.

4. The method of claim 1 , wherein the CHK1 Inhibitor is (R)—N-(5-bromo-4-(3-(methylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide.

5. The method of claim 1 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methylnicotinamide.

6. The method of claim 1 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide.

7. The method of claim 1 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbutanamide.

8. The method of claim 1 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyclopropylacetamide.

9. The method of claim 1 , wherein the doses of the CHK1 Inhibitor are administered between the biologically effective dose and the maximum tolerated dose.

10. The method of claim 1 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine, irinotecan, temozolomide, capecitabine, topotecan, cisplatin, oxaliplatin, carboplatin, camptothecin, cytarabine, fluorouracil, cyclophosphamide, etoposide phosphate, teniposide, doxorubicin, daunorubicin, pemetrexed, mitomycin C, fludarabine, chlorambucil, melphalan, hydroxyurea, and radiation.

11. The method of claim 1 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine, irinotecan, temozolomide, capecitabine, camptothecin, cisplatin, ara-C, and 5-FU.

12. The method of claim 1 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine, irinotecan, temozolomide and capecitabine.

13. The method of claim 1 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine, irinotecan, cisplatin, oxaliplatin, carboplatin and cytarabine.

14. The method of claim 1 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine and irinotecan.

15. A method for treating cancer by administering a DNA damaging agent and three doses of a CHK1 inhibitor selected from (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide and (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)isobutyramide, (R)—N-(5-bromo-4-(3-(methylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide, (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methylnicotinamide, (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide, (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbutanamide, and (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyclopropylacetamide, wherein the first dose of the CHK1 inhibitor is administered one day after the DNA damaging agent, the second dose of the CHK1 inhibitor is administered two days after the DNA damaging agent, and the third dose of the CHK1 inhibitor is administered three days after the DNA damaging agent.

16. The method of claim 15 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide.

17. The method of claim 15 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)isobutyramide.

18. The method of claim 15 , wherein the CHK1 Inhibitor is (R)—N-(5-bromo-4-(3-(methylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide.

19. The method of claim 15 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methylnicotinamide.

20. The method of claim 15 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide.

21. The method of claim 15 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbutanamide.

22. The method of claim 15 , wherein the CHK1 Inhibitor is (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyclopropylacetamide.

23. The method of claim 15 , wherein the doses of the CHK1 Inhibitor are administered between the biologically effective dose and the maximum tolerated dose.

24. The method of claim 15 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine, irinotecan, temozolomide, capecitabine, topotecan, cisplatin, oxaliplatin, carboplatin, camptothecin, cytarabine, fluorouracil, cyclophosphamide, etoposide phosphate, teniposide, doxorubicin, daunorubicin, pemetrexed, mitomycin C, fludarabine, chlorambucil, melphalan, hydroxyurea, and radiation.

25. The method of claim 15 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine, irinotecan, temozolomide, capecitabine, camptothecin, cisplatin, ara-C, and 5-FU.

26. The method of claim 15 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine, irinotecan, temozolomide and capecitabine.

27. The method of claim 15 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine, irinotecan, cisplatin, oxaliplatin, carboplatin and cytarabine.

28. The method of claim 15 , wherein the DNA damaging agent is selected from the group consisting of gemcitabine and irinotecan.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 8, 2010
From: HUMPHRIES, MICHAEL J.; WINSKI, SHANNON L.
To: ARRAY BIOPHARMA, INC.
Reel/Frame 024502/0448 →
Continuity (2)
Provisional Application 61168564 · Apr 11, 2009
Related Publication 20100260868A1 · Oct 14, 2010