Treating and preventing diseases by modulating cell mechanics

Patent metadata

Field	Value
Publication number	US-10787410-B2
Application number	US-201815946849-A
Country	US
Kind code	B2
Filing date	Apr 6, 2018
Priority date	Dec 16, 2013
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

Abstract

Described are methods of treating or preventing a disease in a subject treatable by modulating cell mechanics. The method includes administering to a subject having or at risk for such a disease a pharmaceutical composition comprising an agent selected from the group comprising a salt, solvate, or stereoisomer of compound (VIII) or its derivatives or a mixture of their constituents, where the compound has the formula:

First claim

The invention claimed is:

1. A method for modulating cell mechanics in a disease cell that expresses nonmuscle myosin IIB, nonmuscle myosin IIC, or a combination thereof, in a subject comprising the step of administering to the subject, an effective amount of a pharmaceutical composition comprising a compound (V) or a salt or solvate, thereof where the compound (V) has the formula:

wherein R 1 , R 2 , R 3 and R 4 are H, and wherein X is C 1 -C 3 alkyl,
and wherein the nonmuscle myosin IIB, the nonmuscle myosin IIC, or a combination thereof, in the subject is activated, and wherein the cell mechanics in the disease cell of the subject are modulated, and wherein the disease cell is selected from the group consisting of a cell from a pancreatic cancer and a cell from a renal cancer.

2. The method of claim 1 wherein myosin II is activated in the subject compared to a reference subject that has not been administered the effective amount of compound (V).

3. The method of claim 1 , wherein the method of administering is systemic delivery selected from the group consisting of oral, parenteral, intranasal, sublingual, rectal, and transdermal administration.

4. The method of claim 1 , further comprising the step of administering a bioactive agent.

5. The method of claim 4 , wherein the bioactive agent is a compound having a formula:

6. The method of claim 4 , wherein the bioactive agent is a chemotherapy agent.

7. The method of claim 1 , wherein X is methyl.

8. A method for treating cancer that expresses nonmuscle myosin IIB, nonmuscle myosin IIC, or a combination thereof, in a subject comprising the step of:
administering to the subject having cancer, an effective amount of a pharmaceutical composition comprising a compound (V) or a salt or solvate, thereof where the compound (V) has the formula:

wherein R 1 , R 2 , R 3 and R 4 are H, and wherein X is C 1 -C 3 alkyl,
and wherein the nonmuscle myosin IIB, the nonmuscle myosin IIC, or a combination thereof, in the subject is activated, and wherein the cancer is pancreatic cancer or renal cancer.

9. The method of claim 8 , wherein X is methyl.

10. The method of claim 8 , further comprising the step of administering a bioactive agent.

11. The method of claim 10 , wherein the bioactive agent is a compound having a formula:

12. The method of claim 10 , wherein the bioactive agent is a chemotherapy agent.

Assignees

• Univ Johns Hopkins

Inventors

• Robinson Douglas
• Surcel Alexandra
• Ng Win Pin
• Freel Meyers Caren L

Classifications

• A61K31/136 Primary

  having the amino group directly attached to the aromatic ring, e.g. benzeneamine · CPC title

• C07C275/30

  being further substituted by halogen atoms, or by nitro or nitroso groups · CPC title

• G01N2333/4712

  Muscle proteins, e.g. myosin, actin, protein · CPC title

• C07C49/825 Primary

  all hydroxy groups bound to the ring · CPC title

• G01N2333/44

  from protozoa · CPC title