Transient protection of normal cells during chemotherapy

Patent metadata

Field	Value
Publication number	US-2018360840-A1
Application number	US-201816112360-A
Country	US
Kind code	A1
Filing date	Aug 24, 2018
Priority date	Mar 15, 2013
Publication date	Dec 20, 2018
Grant date	—

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

1 . A method of reducing chemotherapeutic agent induced cell damage in hematopoietic stem and progenitor cells (HSPCs) in a human receiving chemotherapy for the treatment of a cancer comprising:
administering to the human an effective amount of a selective CDK4/6 inhibitor of formula:

and,
administering to the human an effective amount of a chemotherapeutic agent;
wherein the selective CDK4/6 inhibitor is administered to the human about 24 hours or less prior to administration of the chemotherapeutic agent.

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

3 . The method of claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of etoposide, carboplatin, gemcitabine, topotecan, paclitaxel, docetaxel, doxorubicin, and a combination thereof.

4 . The method of claim 1 , wherein the cancer is lung cancer.

5 . The method of claim 1 , wherein the cancer is breast cancer.

6 . The method of claim 1 , wherein the cancer is head and neck cancer.

7 . The method of claim 1 , wherein the cancer is cervical cancer.

8 . The method of claim 1 , wherein the cancer is prostate cancer.

9 . The method of claim 1 , wherein the cancer is bladder cancer.

10 . The method of claim 1 , wherein the cancer is colorectal cancer.

11 . The method of claim 4 , wherein the lung cancer is small cell lung cancer.

12 . The method of claim 5 , wherein the breast cancer is triple negative breast cancer.

13 . The method of claim 3 , wherein the chemotherapeutic agent is etoposide.

14 . The method of claim 3 , wherein the chemotherapeutic agent is carboplatin.

15 . The method of claim 3 , wherein the chemotherapeutic agent is gemcitabine.

16 . The method of claim 3 , wherein the chemotherapeutic agent is topotecan.

17 . The method of claim 3 , wherein the chemotherapeutic agent is paclitaxel.

18 . The method of claim 3 , wherein the chemotherapeutic agent is docetaxel.

19 . The method of claim 1 , wherein the chemotherapeutic agent induced cell damage is cell death.

20 . A method of treating a human with cancer comprising:
administering to the human an effective amount of a selective CDK4/6 inhibitor of formula:

and,
administering to the human a chemotherapeutic agent;

wherein the selective CDK4/6 inhibitor is administered to the human about 24 hours or less prior to administration of the chemotherapeutic agent.

21 . The method of claim 20 , wherein the selective CDK4/6 inhibitor is administered to the human about 4 hours or less prior to administration of the chemotherapeutic agent.

22 . The method of claim 20 , wherein the chemotherapeutic agent is selected from the group consisting of etoposide, carboplatin, gemcitabine, topotecan, paclitaxel, docetaxel, doxorubicin, and a combination thereof.

23 . The method of claim 20 , wherein the cancer is lung cancer.

24 . The method of claim 20 , wherein the cancer is breast cancer.

25 . The method of claim 20 , wherein the cancer is head and neck cancer.

26 . The method of claim 20 , wherein the cancer is cervical cancer.

27 . The method of claim 20 , wherein the cancer is prostate cancer.

28 . The method of claim 20 , wherein the cancer is bladder cancer.

29 . The method of claim 20 , wherein the cancer is colorectal cancer.

30 . The method of claim 23 , wherein the lung cancer is small cell lung cancer.

31 . The method of claim 24 , wherein the breast cancer is triple negative breast cancer.

32 . The method of claim 22 , wherein the chemotherapeutic agent is etoposide.

33 . The method of claim 22 , wherein the chemotherapeutic agent is carboplatin.

34 . The method of claim 22 , wherein the chemotherapeutic agent is gemcitabine.

35 . The method of claim 22 , wherein the chemotherapeutic agent is topotecan.

36 . The method of claim 22 , wherein the chemotherapeutic agent is paclitaxel.

37 . The method of claim 22 , wherein the chemotherapeutic agent is docetaxel.

Assignees

• G1 Therapeutics Inc

Inventors

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

Classifications

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K31/5377

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

• A61P35/04

  specific for metastasis · CPC title

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61P35/00

  Antineoplastic agents · CPC title