Synthetic binder of breast cancer stem cells

Patent metadata

Field	Value
Publication number	US-11091516-B2
Application number	US-202016739516-A
Country	US
Kind code	B2
Filing date	Jan 10, 2020
Priority date	Jan 11, 2019
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

The present disclosure provides a for peptoid compounds that bind selective to cancer stem cells (CSCs), particularly those associated with breast cancer. Conjugates of the peptoids to detactable labels and therapeutic agent are contemplated as are methods of diagnosing and treating breast cancer.

First claim

What is claimed:

1. A compound having the formula:

2. The compound of claim 1 , wherein said compound is linked through the terminal amide group to a detectable agent, a therapeutic agent, or a scaffold.

3. The compound of claim 1 , wherein said compound is modified to contain a sulfhydryl functional group and conjugated to a detectable agent, a therapeutic agent, or a scaffold via a thioether linkage, wherein the detectable agent, therapeutic agent, or scaffold comprise sulfhydryl reactive molecules.

4. The compound of claim 3 , wherein the sulfhydryl functional group is from a cysteine.

5. The compound of claim 3 , wherein the detectable agent, therapeutic agent, or scaffold is attached via a maleimide.

6. A method of binding a compound to a cancer stem cell (CSC) comprising contacting a composition of claims 1 - 3 with a CSC.

7. The method of claim 6 , wherein the CSC exhibits a phenotype of CD24 − , CD44+ and/or ALDH+.

8. The method of claim 6 , wherein the CSC is a breast CSC.

9. The method of claim 8 , wherein the breast CSC is Her2/Neu negative or hormone receptor negative.

10. The method of claim 8 , wherein the breast CSC is hormone receptor negative and Her2/Neu negative.

11. A method of identifying a cancer stem cell (CSC) in a subject with breast cancer comprising contacting said subject or a sample from said subject with a compound having the formula:

conjugated to a detectable agent.

12. The method of claim 11 , further comprising treating said subject for cancer following detection of a CSC.

13. A method of treating a subject with breast cancer comprising contacting said subject with a compound or compounds having the formula:

conjugated to a therapeutic agent.

14. The method of claim 13 , wherein said breast cancer is primary, recurrent, metastatic or drug resistant.

15. The method of claim 13 , wherein said breast cancer is hormone receptor negative.

16. The method of claim 13 , wherein the breast cancer is Her2/Neu negative.

17. The method of claim 13 , wherein the breast cancer is hormone receptor negative and Her2/Neu negative.

18. The method of claim 13 , further comprising treating said subject with a second cancer therapy.

19. The method of claim 18 , wherein said second distinct cancer therapy is radiotherapy, chemotherapy, immunotherapy, toxin therapy, hormonal therapy or surgery.

20. The method of claim 13 , wherein said therapeutic agent is a radioisotope, chemotherapeutic agent, immunotherapeutic agent, a toxin, or hormonal therapeutic.

21. The method of claim 13 , wherein said therapeutic agent is a hyperthermal therapeutic agent.

22. The method of claim 21 , wherein the hyperthermal therapeutic agent is a gold nanorod.

23. The method of claim 13 , wherein said subject is treated with more than one of said compounds.

24. The method of claim 23 , wherein said subject is treated weekly, monthly or chronically.

Assignees

• Univ Texas

Inventors

• Lee Jiyong
• Chen Luxi
• Long Chao
• Qin Zhenpeng
• Youn Jonghae
• Kang Peiyuan

Classifications

• G01N33/57515

  of the breast · CPC title

• A61K47/6925

  the form being a microcapsule, nanocapsule, microbubble or nanobubble · CPC title

• A61K41/0052

  Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy · CPC title

• A61K33/242

  Gold; Compounds thereof · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title