Agent for controlling cells constituting cancer microenvironment or inflammatory microenvironment

An agent for controlling cells constituting a cancer microenvironment or inflammatory microenvironment, said agent comprising as an effective component any of the following (1) to (3):

• (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate;
• (2) a pharmaceutically acceptable salt of (1);
• (3) a solvate of (1) or (2).

An agent for inhibiting interaction between CCR2B or CCR5 and FROUNT protein, said agent comprising as an effective component any of the following (1) to (3):

• (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate;
• (2) a pharmaceutically acceptable salt of (1);
• (3) a solvate of (1) or (2).

An agent for enhancing anticancer activity of an anticancer drug, said agent comprising as an effective component any of the following (1) to (3):

• (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate;
• (2) a pharmaceutically acceptable salt of (1);
• (3) a solvate of (1) or (2).

A method for identifying a disulfiram derivative having an improved ability to inhibit interaction between FROUNT protein and CCR2B or CCR5, said method comprising the steps of:

• incubating a FROUNT protein fragment containing the region of the 564th to 600th amino acids of FROUNT protein, and a CCR2B fragment containing the region of the 312th to 323rd amino acids in the amino acid sequence of CCR2B shown in SEQ ID NO:6 or a CCR5 fragment containing the region of the 304th to 315th amino acids in the amino acid sequence of CCR5 shown in SEQ ID NO:8, together with a disulfiram derivative library;
• and
• selecting a disulfiram derivative having a higher activity to inhibit binding of the FROUNT protein fragment to the CCR2B fragment or CCR5 fragment compared to disulfiram.

A method for identifying a compound having an improved ability to inhibit interaction between FROUNT protein and CCR2B or CCR5, said method comprising the steps of:

• incubating a FROUNT protein fragment containing the region of the 564th to 600th amino acids of FROUNT protein, and a CCR2B fragment containing the region of the 312th to 323rd amino acids in the amino acid sequence of CCR2B shown in SEQ ID NO:6 or a CCR5 fragment containing the region of the 304th to 315th amino acids in the amino acid sequence of CCR5 shown in SEQ ID NO:8, together with a library of derivatives of a candidate FROUNT inhibitor compound;
• and
• selecting a derivative having a higher activity to inhibit binding of the FROUNT protein fragment to the CCR2B fragment or the CCR5 fragment compared to the original candidate compound.

A method for designing a substance that inhibits interaction between FROUNT protein and CCR2B or CCR5, said method comprising:

• allowing a candidate compound to bind in silico to a binding pocket structure in which FROUNT protein binds to CCR2B or CCR5;
• and
• calculating the strength of the binding.

A method for inhibiting macrophages, said method comprising administering an effective amount of any of the following (1) to (3) to a subject in need thereof:

• (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate;
• (2) a pharmaceutically acceptable salt of (1);
• (3) a solvate of (1) or (2).

A method for inhibiting cells constituting a cancer microenvironment or inflammatory microenvironment, said method comprising administering an effective amount of any of the following (1) to (3) to a subject in need thereof:

• (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate;
• (2) a pharmaceutically acceptable salt of (1);
• (3) a solvate of (1) or (2).

A method for inhibiting interaction between CCR2B or CCR5 and FROUNT protein, said method comprising administering an effective amount of any of the following (1) to (3) to a subject in need thereof:

• (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate;
• (2) a pharmaceutically acceptable salt of (1);
• (3) a solvate of (1) or (2).

A method for enhancing anticancer activity of an anticancer drug, said method comprising administering an effective amount of any of the following (1) to (3) to a subject in need thereof:

• (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate;
• (2) a pharmaceutically acceptable salt of (1);
• (3) a solvate of (1) or (2).