THERAPEUTIC TARGETING OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 (IRAK4) IN CANCERS CHARACTERIZED BY REARRANGEMENTS IN THE MIXED LINEAGE LEUKEMIA GENE (MLL-r)

• US 20180319795A1
• Filed: 07/09/2018
• Published: 11/08/2018
• Est. Priority Date: 04/26/2016
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Shilatifard, Ali, Liang, Kaiwei, Smith, Edwin Richard
• Granted Patent: US 10,640,502 B2
• Time in Patent Office: Days
• CPC Class Codes: C07D 233/88 Nitrogen atoms, e.g. allantoin
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Disclosed are methods for treating cancers associated with rearrangements in the mixed lineage leukemia gene (MLL-r), including MLL-r leukemia. The methods typically include administering a therapeutic amount of one or more therapeutic agents that inhibit the biological activity of one or more members of the interleukin-1 signaling pathway such inhibitors of interleukin-1 receptor-associated kinase 4 (IRAK4).

Claims

1. A method for treating a cancer characterized by a rearrangement in the mixed lineage leukemia gene (MLL-r) in a subject in need thereof, the method comprising administering a therapeutic amount of a therapeutic agent that inhibits the biological activity of interleukin-1 receptor-associated kinase 4 (IRAK4).

2. The method of claim 1, wherein the cancer is MLL-r leukemia.

3. The method of claim 1, wherein the therapeutic agent is a compound having a formula III:

4. The method of claim 3, wherein the compound has a formula IIIa:

5. The method of claim 4, wherein the compounds has a formula IIIb:

6. The method of claim 5, wherein the compound has a formula selected from:

7. The method of claim 1, wherein the compound has a formula IV:

8. The method of claim 7, wherein the compound has a formula IVa:

9. The method of claim 8, wherein the compound has a formula selected from:

10. The method of claim 1, wherein the therapeutic agent is a compound having the formula I:

11. The method of claim 1, wherein the therapeutic agent is a compound having the formula II:

12. A compound having a formula III:

13. The compound of claim 12, wherein the compound has a formula

14. The compound of claim 13, wherein the compounds has a formula IIIb:

15. The compound of claim 14, wherein the compound has a formula selected from:

19. A pharmaceutical composition comprising the compound of claim 12 and a pharmaceutically acceptable carrier.

16. A compound having a formula IV:

17. The compound of claim 16, wherein the compound has a formula IVa:

18. The compound of claim 17, wherein the compound has a formula selected from:

20. A pharmaceutical composition comprising the compound of claim 16 and a pharmaceutically acceptable carrier.