Cytotoxic actin-targeting compounds

Patent metadata

Field	Value
Publication number	US-12239639-B2
Application number	US-202217849949-A
Country	US
Kind code	B2
Filing date	Jun 27, 2022
Priority date	Aug 18, 2017
Publication date	Mar 4, 2025
Grant date	Mar 4, 2025

Abstract

A class of compounds useful in pharmaceutical compositions and methods for treating or preventing cancer is described. Analogs of Mycalolide B have been prepared and tested in breast and ovarian cancer cell lines. The compounds show utility for inhibition of survival and proliferation of tumor cells. The compounds have been shown to disrupt actin.

First claim

We claim:

1. A compound MA-02-058

2. A pharmaceutical composition, comprising an effective amount of a compound MA-02-058 or a pharmaceutically acceptable salt thereof

3. The pharmaceutical composition of claim 2 , for the treatment and/or mitigation of cancer.

4. The pharmaceutical composition of claim 3 , wherein the cancer is breast cancer, ovarian cancer, lung cancer, pancreatic cancer, melanoma, colorectal cancer, kidney cancer, cervical cancer, testicular cancer, or liver cancer.

5. The pharmaceutical composition of claim 2 , for suppressing metastatic cancer cell motility, survival, or both, further comprising a pharmaceutically acceptable vehicle.

6. The pharmaceutical composition of claim 2 , further comprising one or more antineoplastic agent(s).

7. The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition further comprises a protein or a glycosaminoglycan.

8. The pharmaceutical composition of claim 7 , wherein the protein is an antibody, hemoglobin, alphafeto-protein, fibrinogen, or serum albumin.

9. The pharmaceutical composition of claim 7 , wherein the glycosaminoglycan comprises hyaluronic acid.

10. A method of inhibiting actin in a subject in need thereof, comprising administering to a subject the compound MA-02-058 of claim 1 .

11. The method of claim 10 , wherein the subject has inflammatory lung disease.

12. A method of reducing actin released into circulation upon cellular damage, comprising administering the pharmaceutical composition of claim 2 , to a subject in need thereof.

13. A method of suppressing tumor growth, metastasis, or both, comprising administering the pharmaceutical composition of claim 2 , to a subject in need thereof.

14. A method of treating and/or mitigating cancer or a cell proliferation disorder, in a subject in need thereof, comprising administering to a subject the compound MA-02-058 of claim 1 .

15. The method of claim 14 , wherein the cancer is breast cancer, ovarian cancer, lung cancer, pancreatic cancer, melanoma, colorectal cancer, kidney cancer, cervical cancer, testicular cancer, or liver cancer.

Assignees

• Univ Kingston

Inventors

• Grange Rebecca
• Allingham John
• Craig Andrew
• Evans P Andrew
• Aeluri Madhu

Classifications

• C07D307/46

  Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom · CPC title

• C07D211/76

  attached in position 2 or 6 · CPC title

• C07D207/27

  with substituted hydrocarbon radicals directly attached to the ring nitrogen atom · CPC title

• C07D205/08

  with one oxygen atom directly attached in position 2, e.g. beta-lactams · CPC title

• C07C321/10

  of an unsaturated carbon skeleton containing rings · CPC title