Screening method of anticancer agent focused on function of HP1 and evaluation system

Patent metadata

Field	Value
Publication number	US-11340215-B2
Application number	US-201716079895-A
Country	US
Kind code	B2
Filing date	Feb 27, 2017
Priority date	Feb 26, 2016
Publication date	May 24, 2022
Grant date	May 24, 2022

Abstract

The inventors have found that the interaction between HP1 and INCENP can serve as an indicator for chromosome instability and established a method for evaluating chromosome instability of cancer cells. The evaluation system can be used for screening of anticancer agent with a new-concept of targeting chromosome instability of cancer cells. The inventors further prepared an antibody for specifically recognizing phosphorylation of serine at position 92 of HP1α, by which the action of Aurora B can be evaluated. The interaction between HP1 and INCENP can be readily evaluated by the antibody.

First claim

The invention claimed is:

1. A method for evaluating chromosome instability to screen for an anticancer agent, comprising:
selecting a compound as an anticancer agent candidate and adding the selected compound to a system comprising heterochromatin protein 1 (HP1) and inner centromere protein (INCENP), wherein the HP1 and the INCENP are allowed to bind to each other;
determining a change of interaction or binding of HP1α to the INCENP in the system with the selected compound added; and
evaluating chromosome instability based on the determined change of interaction or binding of the HP1α to the INCENP, wherein if the determined change of interaction or binding is decreased, the chromosome instability is evaluated as being increased, to screen the selected compound as the anticancer agent;
wherein the system is one of a binding assay system or an alpha assay system.

2. The method for evaluating chromosome instability according to claim 1 , wherein
determining the change of interaction or binding of HP1α to INCENP includes analyzing phosphorylation of HP 1 a to determine binding of HP1α to CPC (chromosomal passenger complex) and Aurora B activity, wherein the phosphorylation of HP1α is phosphorylation of serine at position 92 of HP1α.

3. The method for evaluating chromosome instability to screen for an anticancer agent according to claim 1 , further comprising:
measuring accuracy of chromosome segregation with the selected compound during cell division by imaging analysis.

Assignees

• Japanese Found For Cancer Res

Inventors

• Hirota Toru
• Abe Yusuke

Classifications

• G01N33/575

  for cancer · CPC title

• C07K16/18 Primary

  against material from animals or humans · CPC title

• G01N33/6845

  Methods of identifying protein-protein interactions in protein mixtures · CPC title

• C07K2317/30

  characterized by aspects of specificity or valency · CPC title

• G01N33/5011 Primary

  for testing antineoplastic activity · CPC title