Method of inhibiting cancer cell, method for detecting cancer cell, and system for detecting cancer cell

Patent metadata

Field	Value
Publication number	US-10220024-B2
Application number	US-201615351683-A
Country	US
Kind code	B2
Filing date	Nov 15, 2016
Priority date	Oct 26, 2012
Publication date	Mar 5, 2019
Grant date	Mar 5, 2019

Abstract

An object of the present invention is to provide a cancer cell inhibitory drug, particularly a cancer stem-cell inhibitory drug, or a cancer stem-cell detection probe. A cancer cell inhibitory drug containing at least a compound represented by general formula (1).

First claim

The invention claimed is:

1. A method of inhibiting growth of a cancer cell, which is at least one selected from the group consisting of a pancreatic cancer cell, a prostatic cancer cell, and a chronic myelocytic leukemia cell, in a subject in need thereof, the method comprising administering to the subject a composition comprising, as an active ingredient, a compound represented by general formula (1):

where R 1 independently represents an alkyl group, a carboxylalkyl group, an alkoxycarbonylalkyl group, or an alkylcarbonyloxyalkyl group; R 2 to R 5 each independently represents a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, a halogen atom, an alkoxysulfonyl group, a N-alkylsulfamoyl group, an alkyloxycarbonyl group, or a N-alkylcarbamoyl group; R 6 and R 7 each independently represents a hydrogen atom, an alkyl group, or a phenyl group; R 8 represents a hydrogen atom, an alkyl group, an alkenyl group, or a halogen atom; R 11 represents an alkyl group, an aryl group, or an aralkyl group; X 1 − represents an anionic group;
A represents a cyclopentane ring or a benzene ring;
Y 1 represents an oxygen atom, a sulfur atom, a nitrogen atom binding to an alkyl group or —C(R 12 )(R 13 )—, where R 12 and R 13 each independently represents an alkyl group, or R 12 and R 13 bind together to form an aliphatic ring; and
L is absent and carbons at both sides of L are bound through a double bond, is represented by general formula (2), or represents ═C(R 15 )—C(R 16 )═, where R 15 and R 16 each independently represents a hydrogen atom or an alkyl group:

where R 14 represents an alkyl group, a carboxylalkyl group, an alkoxycarbonylalkyl group, or an alkylcarbonyloxyalkyl group.

2. The method according to claim 1 , wherein the compound represented by the general formula (1) is a compound represented by general formula (3):

where R 17 each independently represents an alkyl group, a carboxylalkyl group, an alkoxycarbonylalkyl group, or an alkylcarbonyloxyalkyl group; R 18 to R 21 each independently represents a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, a halogen atom, an alkoxysulfonyl group, a N-alkylsulfamoyl group, an alkyloxycarbonyl group, or a N-alkylcarbamoyl group; R 22 and R 23 each independently represents a hydrogen atom, an alkyl group, or a phenyl group; R 24 represents a hydrogen atom or a halogen atom; R 25 represents an alkyl group, an aryl group, or an aralkyl group; X 2 − represents an anionic group;
Y 2 represents an oxygen atom, a sulfur atom, a nitrogen atom binding to an alkyl group, or —C(R 26 )(R 27 )—, where R 26 and R 27 each independently represents an alkyl group, or R 26 and R 27 bind together to form an aliphatic ring; and
A represents a cyclopentane ring or a benzene ring.

3. The method according to claim 1 , wherein the compound represented by the general formula (1) is a compound represented by general formula (4):

where R 28 each independently represents an alkyl group, a carboxylalkyl group, an alkoxycarbonylalkyl group, or an alkylcarbonyloxyalkyl group; R 29 to R 32 each independently represents a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, a halogen atom, an alkoxysulfonyl group, a N-alkylsulfamoyl group, an alkyloxycarbonyl group, or a N-alkylcarbamoyl group; R 33 and R 34 each independently represents a hydrogen atom, an alkyl group, or a phenyl group; R 35 represents an alkyl group, a carboxylalkyl group, an alkoxycarbonylalkylgroup, or an alkylcarbonyloxyalkyl group; R 36 represents a hydrogen atom or a halogen atom; R 37 represents an alkyl group, an aryl group, or an aralkyl group; X 3 − represents an anionic group;
Y 3 represents an oxygen atom, a sulfur atom, a nitrogen atom binding to an alkyl group or —C(R 38 )(R 39 )—, where R 38 and R 39 each independently represents an alkyl group, or R 38 and R 39 bind together to form an aliphatic ring; and
B represents a cyclopentane ring or a benzene ring.

4. The method according to claim 1 , wherein the compound represented by the general formula (1) is a compound having a luminescence property.

5. The method according to claim 1 , wherein the pancreatic cancer cell, the prostatic cancer cell, or the chronic myelocytic leukemia cell is a cancer stem cell.

6. The method according to claim 1 , wherein the cancer cell is the chronic myelocytic leukemia cell.

7. The method according to claim 1 , wherein the subject is a human.

8. A method for detecting a composition taken into a cancer cell in a subject in need thereof, comprising:
administering to the subject a composition; and
detecting light emitted from the composition taken into the cancer cell,
wherein the cancer cell is at least one selected from the group consisting of a pancreatic cancer cell, a prostatic cancer cell, and a chronic myelocytic leukemia cell,
wherein the composition comprises, as an active ingredient, a compound represented by general formula (1):

where R 1 independently represents an alkyl group, a carboxylalkyl group, an alkoxycarbonylalkyl group, or an alkylcarbonyloxyalkyl group; R 2 to R 5 each independently represents a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, a halogen atom, an alkoxysulfonyl group, a N-alkylsulfamoyl group, an alkyloxycarbonyl group, or a N-alkylcarbamoyl group; R 6 and R 7 each independently represents a hydrogen atom, an alkyl group, or a phenyl group; R 8 represents a hydrogen atom, an alkyl group, an alkenyl group, or a halogen atom; R 11 represents an alkyl group, an aryl group, or an aralkyl group; X 1 − represents an anionic group;
A represents a cyclopentane ring or a benzene ring;
Y 1 represents an oxygen atom, a sulfur atom, a nitrogen atom binding to an alkyl group or —C(R 12 )(R 13 )—, where R 12 and R 13 each independently represents an alkyl group, or R 12 and R 13 bind together to form an aliphatic ring; and
L is absent and carbons at both sides of L are bound through a double bond, is represented by general formula (2), or represents ═C(R 15 )—C(R 16 )═, where R 15 and R 16 each independently represents a hydrogen atom or an alkyl group:

where R 14 represents an alkyl group, a carboxylalkyl group, an alkoxycarbonylalkyl group, or an alkylcarbonyloxyalkyl group.

9. The method according to claim 8 , wherein the compound represented by the general formula (1) is a compound represented by general formula (3):

where R 17 each independently represents an alkyl group, a carboxylalkyl group, an alkoxycarbonylalkyl group, or an alkylcarbonyloxyalkyl group; R 18 to R 21 each independently represents a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, a halogen atom, an alkoxysulfonyl group, a N-alkylsulfamoyl group, an alkyloxycarbonyl group, or a N-alkylcarbamoyl group; R 22 and R 23 each independently represents a hydrogen atom, an alkyl group, or a phenyl g

Assignees

• Canon Kk

Inventors

• Shintou Taichi
• Nomoto Tsuyoshi
• Watanabe Kohei
• Miyazaki Takeshi
• Tanaka Toshio
• Shimada Yasuhito
• Nishimura Yuhei

Classifications

• A61K49/0032

  Methine dyes, e.g. cyanine dyes · CPC title

• A61K41/0038

  Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10) · CPC title

• A61K31/423

  condensed with carbocyclic rings · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title