IP Library › Granted Patent US 9,155,726
Granted Patent B2
US 9,155,726 · App. 13/913,091 · Granted Oct 13, 2015

Method of treatment using checkpoint kinase 1 inhibitors

Inventors: Michael J. Humphries (Boulder, CO); Shannon L. Winski (Boulder, CO)
Assignee: Array BioPharma Inc.
A61K31/437A61K31/4375A61K31/4545A61K31/4745A61K31/513A61K31/519A61K31/664A61K31/704A61K31/7068A61K31/7076A61K33/24A61K45/06
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Quick Facts
Patent No.
US 9,155,726
App. No.
13/913,091
Granted
Oct 13, 2015
Kind
B2
Abstract

Methods of treating cancer by administering a DNA damaging agent and a CHK1 Inhibitor on a dosing regimen are provided.

Claims (28)

1. A method for treating cancer comprising administering a DNA damaging agent followed by four doses of a CHK1 inhibitor, wherein the first two doses of the CHK1 inhibitor are administered one day after the DNA damaging agent, and the third and fourth doses of the CHK1 inhibitor are administered two days after the DNA damaging agent, and wherein said CHK1 inhibitor is selected from the group consisting of: (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-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)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.

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)isobutyramide.

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, 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 comprising administering a DNA damaging agent followed by six doses of a CHK1 inhibitor, wherein the first two doses of the CHK1 inhibitor are administered one day after the DNA damaging agent, the third and fourth doses of the CHK1 inhibitor are administered two days after the DNA damaging agent, and the fifth and sixth dose of the CHK1 inhibitor are administered three days after the DNA damaging agent, and wherein said CHK1 inhibitor is selected from the group consisting of: (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-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)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.

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, 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 (3)
RELEASE OF SECURITY INTEREST Recorded May 19, 2016
From: PACIFIC WESTERN BANK (AS SUCCESSOR IN INTEREST BY MERGER TO SQUARE 1 BANK)
To: METABOLIC SOLUTIONS DEVELOPMENT COMPANY, LLC
Reel/Frame 038652/0097 →
SECURITY INTEREST Recorded Jan 4, 2016
From: METABOLIC SOLUTIONS DEVELOPMENT COMPANY, LLC
To: PACIFIC WESTERN BANK (AS SUCCESSOR IN INTEREST BY MERGER TO SQUARE 1 BANK)
Reel/Frame 037401/0277 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 26, 2013
From: HUMPHRIES, MICHAEL J.; WINSKI, SHANNON L.
To: ARRAY BIOPHARMA INC.
Reel/Frame 031082/0801 →
Continuity (3)
Continuation 12757954 · Apr 9, 2010
Provisional Application 61168564 · Apr 11, 2009
Related Publication 20140045782A1 · Feb 13, 2014