Methods of treating cancer

Patent metadata

Field	Value
Publication number	US-2020330486-A1
Application number	US-201816772755-A
Country	US
Kind code	A1
Filing date	Dec 14, 2018
Priority date	Dec 15, 2017
Publication date	Oct 22, 2020
Grant date	—

Abstract

The present invention relates to methods of treating cancer comprising administering a bufalin derivative compound of Formula I, wherein the compound is administered at least once a week for at least two weeks.

First claim

1 . A method of treating cancer in an individual, comprising administering to the individual an effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
Z is —OR 1 or —NR 2 R 3 ;
R 1 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
R 2 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; and
R 3 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl,
or R 2 and R 3 are taken together with the atom to which they are attached to form an optionally substituted heterocycloalkyl;
and the compound is administered at least once a week for at least two weeks.

2 . (canceled)

3 . The method of claim 1 , wherein the compound is administered at least three times a week.

4 . The method of claim 3 , wherein the compound is administered for at least three consecutive days during a week or once every other day during a week.

5 - 8 . (canceled)

9 . The method of claim 3 , wherein the compound is administered daily for at least two weeks.

10 . The method of claim 1 , wherein the compound is administered at least once a week for at least two weeks.

11 . (canceled)

12 . The method of claim 10 , wherein the compound is administered at least once a week for two weeks with one week of rest in a 21-day dosage cycle.

13 . (canceled)

14 . The method of claim 1 , wherein the compound is administered at the dosage range of about 0.02 mg/m 2 to about 2 mg/m 2 .

15 - 16 . (canceled)

17 . The method of claim 1 , wherein the cancer is selected from the group consisting of colorectal cancer, liver cancer, lung cancer, breast cancer, prostate cancer, pancreatic cancer, gastric cancer, and non-small cell lung cancer, and oral cancer.

18 . (canceled)

19 . The method of claim 1 , wherein the cancer is locally advanced or metastatic cancer.

20 . The method of claim 1 , wherein the compound is administered intravenously.

21 . The method of claim 20 , wherein the compound is administered by infusion for at least 30 minutes at each administration.

22 - 23 . (canceled)

24 . The method of claim 1 , wherein the individual has a high level of PI3K and/or pAKT.

25 . The method of claim 1 , wherein the individual has progressed on or failed at least one prior systemic therapy.

26 . The method of claim 1 , wherein the compound is administered at the concentration of about 0.002 mg/mL to about 0.01 mg/mL.

27 . The method of claim 1 , wherein the compound is in a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier.

28 . (canceled)

29 . The method of claim 1 , wherein the individual is human.

30 . The method of claim 1 , wherein the compound is of Formula I, or a pharmaceutically acceptable salt thereof, wherein Z is —OR 1 and R 1 is optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted heterocycloalkyl.

31 . (canceled)

32 . The method of claim 1 , wherein the compound is of Formula I, or a pharmaceutically acceptable salt thereof, wherein;
Z is —NR 2 R 3 ; R 2 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted heterocycloalkyl, and R 3 is optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted heterocycloalkyl, or R 2 and R 3 are taken together with the atom to which they are attached to form a 4- to 8-membered heterocycloalkyl.

33 . (canceled)

34 . The method of claim 32 , wherein R 2 is hydrogen and R 3 is optionally substituted alkyl.

35 . (canceled)

36 . The method of claim 1 , wherein the compound is selected from Compound Nos. 1-7, or a pharmaceutically acceptable salt thereof:

Assignees

• Neupharma Inc

Inventors

• Qian Xiangping

Classifications

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title

• A61K31/585 Primary

  containing lactone rings, e.g. oxandrolone, bufalin · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• 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

• A61P31/00 Primary

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title