Transient protection of normal cells during chemotherapy

Patent metadata

Field	Value
Publication number	US-11717523-B2
Application number	US-202117222873-A
Country	US
Kind code	B2
Filing date	Apr 5, 2021
Priority date	Mar 15, 2013
Publication date	Aug 8, 2023
Grant date	Aug 8, 2023

Abstract

This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

First claim

The invention claimed is:

1. A method of reducing chemotherapy-induced myelosuppression in a human receiving chemotherapy for the treatment of small cell lung cancer comprising administering to the human an effective amount of at least one chemotherapeutic agent and an effective amount of a CDK4/6 inhibitor of the structure

or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered 24 hours or less prior to administration of the chemotherapeutic agent.

2. The method of claim 1 , wherein the CDK4/6 inhibitor is administered 8 hours or less prior to administration of the chemotherapeutic agent.

3. The method of claim 1 , wherein the CDK4/6 inhibitor is administered 4 hours or less prior to administration of the chemotherapeutic agent.

4. The method of claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of carboplatin, etoposide, cisplatin, topotecan, and a combination thereof.

5. The method of claim 1 , wherein the chemotherapeutic agent is carboplatin.

6. The method of claim 1 , wherein the chemotherapeutic agent is cisplatin.

7. The method of claim 1 , wherein the chemotherapeutic agent is etoposide.

8. The method of claim 1 , wherein the chemotherapeutic agents are carboplatin and etoposide.

9. The method of claim 1 , wherein the chemotherapeutic agents are cisplatin and etoposide.

10. The method of claim 1 , wherein the chemotherapeutic agent is topotecan.

11. A method of reducing chemotherapy-induced myelosuppression in a human receiving chemotherapy for the treatment of small cell lung cancer comprising administering to the human an effective amount of at least one chemotherapeutic agent selected from the group consisting of carboplatin, cisplatin, etoposide, and a combination thereof, and an effective amount of a CDK4/6 inhibitor of the structure

or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered 24 hours or less prior to administration of the chemotherapeutic agent.

12. The method of claim 11 , wherein the CDK4/6 inhibitor is administered 8 hours or less prior to administration of the chemotherapeutic agent.

13. The method of claim 11 , wherein the CDK4/6 inhibitor is administered 4 hours or less prior to administration of the chemotherapeutic agent.

14. The method of claim 11 , wherein the chemotherapeutic agent is carboplatin.

15. The method of claim 11 , wherein the chemotherapeutic agent is cisplatin.

16. The method of claim 11 , wherein the chemotherapeutic agent is etoposide.

17. The method of claim 11 , wherein the chemotherapeutic agents are carboplatin and etoposide.

18. The method of claim 11 , wherein the chemotherapeutic agents are cisplatin and etoposide.

19. A method of reducing chemotherapy-induced myelosuppression in a human receiving chemotherapy for the treatment of small cell lung cancer comprising administering to the human an effective amount of topotecan, and an effective amount of a CDK4/6 inhibitor of the structure

or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered 24 hours or less prior to administration of topotecan.

20. The method of claim 19 , wherein the CDK4/6 inhibitor is administered 8 hours or less prior to administration of the topotecan.

21. The method of claim 19 , wherein the CDK4/6 inhibitor is administered 4 hours or less prior to administration of the topotecan.

Assignees

• G1 Therapeutics Inc

Inventors

• Strum Jay Copeland
• Bisi John Emerson
• Roberts Patrick Joseph
• Tavares Francis Xavier

Classifications

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K31/527 Primary

  spiro-condensed · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title