Prototype systems of theranostic biomarkers for in vivo molecular management of cancer

• US 10,640,524 B2
• Filed: 01/10/2018
• Issued: 05/05/2020
• Est. Priority Date: 06/26/2015
• Status: Active Grant

• Current Assignee: EPOS-Iasis Research and Development, Ltd.
• Original Assignee: EPOS-Iasis Research and Development, Ltd.
• Inventors: Odysseos, Andreani, Pitris, Costas, Keramidas, Anastasios
• Primary Examiner(s): Jarrell, Noble E
• Application Number:
  US15/866,669
• Publication Number:
  US 20180170953A1
• Time in Patent Office: 846 Days
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0052 Small organic molecules oligomers, polymers, dendrimers A61K49/0054
• CPC Class Codes: C07F 15/0053 without a metal-carbon linkage

Abstract

The present invention relates to a theranostic system comprising a beacon and a compound selected from the group consisting of a quinazoline-based tyrosine kinase inhibitor and a natural product. The theranostic systems have use in the therapy and diagnosis of tyrosine kinase related malignancies.

Claims

1. A method of treating and/or diagnosing cancer in a patient in need thereof comprising administering to the patient a theranostic system, the theranostic system comprising a beacon in combination with or covalently linked to at least one compound selected from the group consisting of:

a quinazoline-based tyrosine kinase inhibitor and

a natural product capable of modulating a cancer-related Tyrosine Kinase Receptor (TKR) pathway;

wherein the beacon is a heterometallic compound having a structure define by Formula A

2. The method of claim 1, wherein the cancer is malignant glioma.

3. The method of claim 1, wherein the cancer is colorectal cancer.

4. The method of claim 1, wherein the natural product is (i) a chromanol of the vitamin E superfamily, selected from α

-, β

-, γ

-, and δ

-tocopherols, α

-, β

-, γ

-, and δ

-tocotrienols, and dicarboxylic esters thereof.

5. The method of claim 1, wherein the quinazoline-based tyrosine kinase inhibitor is an anilinoquinazoline-based tyrosine kinase inhibitor having the structure defined by Formula II

6. The method of claim 1, wherein R^1e represents a hydrogen atom and R^1f represents an optionally substituted aryl, aralkyl, heterocyclyl or heterocyclylalkyl group.

7. The method of claim 5, wherein R^1f represents

8. The method of claim 5, wherein R^1f represents a 2-methoxyphenyl, 2-bromophenyl, 2-fluorophenyl, 2-chlorophenyl, 3-methoxyphenyl, 3-bromophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,5,difluorophenyl, 3,5,dichlorophenyl, 3,5,dibromophenyl, 3-(trifluoromethyl)phenyl, 4-chloro-3-(trifluoromethyl)phenyl, 3-chloro-4-fluorophenyl, 4-fluoro-3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-methoxyphenyl, 4-bromophenyl, 4-chlorophenyl, 4-isopropylphenyl, 3-bromo-5-(trifluoromethyl) phenyl, bis(trifluoromethyl)phenyl, 4-(tert-butyl)phenyl or 1-napthylmethyl moiety.

9. The method of claim 1, wherein R² represents a hydrogen atom, a halogen atom, OR^c, N(R^c)(R^d), SR^c or an optionally substituted alkyl group;

wherein R^c and R^d each independently represent a hydrogen atom or an optionally substituted alkyl or acyl group.

10. The method of claim 1, wherein R³ represents a hydrogen atom, OR^g, N(R^g)(R^h), SR or an optionally substituted alkyl, alkenyl or alkynyl group;

wherein R^g and R^h each independently represent a hydrogen atom or an optionally substituted alkyl, acyl, alkenyl or alkynyl group.

11. The method of claim 1, wherein the system comprises a complex of Formula B

12. The method of claim 1, wherein the system comprises a complex of Formula III or Formula IV

13. The method of claim 1, wherein the system comprises a complex of the natural product and the beacon represented by Formula H

14. The method of claim 1, wherein the theranostic system comprises said beacon in combination with or complexed to said natural product.

15. The method of claim 1, wherein the theranostic system comprises said beacon in combination with or complexed to said quinazoline-based tyrosine kinase inhibitor and further comprising said natural product.

16. The method of claim 1, wherein the method comprises detecting the beacon by using one or more imaging technique selected from the group consisting of optical imaging, radiofrequency imaging, magnetic resonance imaging, or positron emission tomography, alone or in combination.