Fluorescent probe sensing tyrosine kinase and use thereof

Patent metadata

Field	Value
Publication number	US-2016116455-A1
Application number	US-201414888883-A
Country	US
Kind code	A1
Filing date	Mar 10, 2014
Priority date	May 10, 2013
Publication date	Apr 28, 2016
Grant date	—

Abstract

A fluorescent probe for detecting a tyrosine kinase using a compound having an ortho-hydroxy-benzaldehyde structure, and use thereof are provided. The fluorescent probe can show a change in fluorescence when the compound binds with a tyrosine kinase. The compound can be readily synthesized and has high stability and low cytotoxicity in vivo. The fluorescent probe can be used to image cells or tissues overexpressing the tyrosine kinase, the fluorescent probe can be effectively used in a composition for imaging the tissues and a method of imaging the tissues. Also, the fluorescent probe can be used to image cancer cells or tissues since the fluorescent probe can exhibit fluorescence when the fluorescent probe binds to the cancer cells or tissues overexpressing the tyrosine kinase.

First claim

1 . A fluorescent probe for detecting a tyrosine kinase using a compound represented by the following Formula 1, or an analogue thereof.

2 . The fluorescent probe of claim 1 , wherein the compound has an ortho-hydroxy-benzaldehyde structure.

3 . The fluorescent probe of claim 1 , wherein the compound exhibits fluorescence when the compound binds to a tyrosine kinase to break an intramolecular hydrogen bond in the ortho-hydroxy-benzaldehyde structure.

4 . The fluorescent probe of claim 1 , wherein the tyrosine kinase is selected from the group consisting of ABL1 (T315I), BRAF, PDGFRa, RSK2, TYK2, and Src.

5 . A method of screening a tyrosine kinase inhibitor using the fluorescent probe defined in claim 1 .

6 . A method of measuring tyrosine kinase activities using the fluorescent probe defined in claim 1 .

7 . A method of single-photon or two-photon imaging cells using the fluorescent probe defined in claim 1 .

8 . A composition for screening a drug inhibiting overexpression of a tyrosine kinase, comprising the fluorescent probe defined in claim 1 .

9 . A composition for imaging cells or tissues overexpressing a tyrosine kinase, comprising the fluorescent probe defined in claim 1 .

10 . The composition of claim 9 , wherein the cells or tissues overexpressing the tyrosine kinase are cancer cells, or cancer tissues.

11 . A method of imaging cells or tissues overexpressing a tyrosine kinase, comprising measuring fluorescence in the cells or tissues using the fluorescent probe defined in claim 1 .

12 . The method of claim 11 , wherein the cells or tissues overexpressing the tyrosine kinase are cancer cells, or cancer tissues.

13 . The method of claim 11 , wherein the measuring of the fluorescence is performed using one or more apparatus selected from the group consisting of a confocal fluorescence microscope, a two-photon fluorescence microscope, and an optical coherence tomograph.

14 . A method of detecting a tyrosine kinase, the method comprising:
causing a compound represented by the following Formula 1 to contact a sample containing a biological material;

measuring fluorescence from the sample that the compound has contacted; and
at least based on measured fluorescence, determining either or both of existence and a level of a tyrosine kinase in the sample.

15 . The fluorescent probe of claim 1 , wherein the compound exhibits changes in fluorescence when an intramolecular hydrogen bond in the ortho-hydroxy-benzaldehyde structure breaks as the compound and a tyrosine kinase bind with each other.

16 . The method of claim 1 , wherein the tyrosine kinase is selected from the group consisting of ABL1 (T315I), BRAF, PDGFRa, RSK2, TYK2, and Src.

Assignees

• Postech Acad Ind Found

Inventors

• Ahn Kyo Han
• Kim Dokyoung
• Kim Sungjee
• Kim Ki Hean

Classifications

• G01N33/575

  for cancer · CPC title

• G01N2333/91205

  Phosphotransferases in general · CPC title

• G01N33/5023 Primary

  on expression patterns · CPC title

• C07C223/06 Primary

  having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton · CPC title

• G01N2333/9121

  with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases · CPC title