Methods for treating melanoma using small molecules

Patent metadata

Field	Value
Publication number	US-11149028-B2
Application number	US-201716469865-A
Country	US
Kind code	B2
Filing date	Dec 15, 2017
Priority date	Dec 15, 2016
Publication date	Oct 19, 2021
Grant date	Oct 19, 2021

Abstract

The invention provides methods for treating cancers, such as melanoma and/or metastatic melanoma, using compounds that interact with and/or inhibit cellular proteins lamin A/C, ATP-dependent RNA helicase DDX1 (DDX1), heterogeneous nuclear ribonuclear protein H1/H2 (hnRNP H2), and/or heterogeneous nuclear ribonuclear protein A2/B1 (hnRNP A2/B1). The invention additionally provides a method for identifying compounds active against melanoma cells.

First claim

What is claimed is:

1. A method for treating metastatic melanoma in a subject in need thereof, the method comprising:
providing a composition including a pharmaceutically acceptable carrier and a therapeutically-effective amount of a compound that interacts with a cellular protein selected from the group consisting of lamin A/C, ATP-dependent RNA helicase DDX1 (DDX1), heterogeneous nuclear ribonuclear protein H1/H2 (hnRNP H2), and heterogeneous nuclear ribonuclear protein A2/B1 (hnRNP A2/B1), the compound having a formula:

in which the R 1 , R 2 , and R 3 positions of the compound is a single amino acid or a mixture of amino acids and the R 4 position of the compound is a single carboxylic acid or a mixture of carboxylic acids; and
administering the composition to the subject.

2. The method according to claim 1 , wherein the subject is a human or an animal.

3. The method according to claim 1 , wherein the compound that interacts with the cellular protein inhibits the cellular protein.

4. The method according to claim 1 , wherein the compound is an antagonist of at least one of lamin A/C, DDX1, hnRNP H2, and hnRNP A2/B1.

5. The method according to claim 1 , wherein the compound is substituted at the R 3 position.

6. The method according to claim 1 , wherein the pharmaceutically acceptable carrier is at least one of a diluent, a binder, a disintegrant, a flavoring, a filler, and a lubricant.

7. The method according to claim 1 , wherein the metastatic melanoma has a mutation in at least one of a BRAF genetic pathway and a NRAS genetic pathway.

8. A method for inhibiting metastatic melanoma cells in a subject in need thereof, the method comprising:
providing a composition including a pharmaceutically acceptable carrier and a therapeutically-effective amount of a compound that inhibits a cellular protein selected from the group consisting of lamin A/C, ATP-dependent RNA helicase DDX1 (DDX1), heterogeneous nuclear ribonuclear protein H1/H2 (hnRNP H2), and heterogeneous nuclear ribonuclear protein A2/B1 (hnRNP A2/B1), the compound having a formula:

wherein the R 1 , R 2 , and R 3 positions of the compound is a single amino acid or a mixture of amino acids and the R 4 position of the compound is a single carboxylic acid or a mixture of carboxylic acids; and
administering the composition to the subject.

9. The method according to claim 8 , wherein the metastatic melanoma cells have a mutation in at least one of a BRAF genetic pathway and a NRAS genetic pathway.

10. The method according to claim 8 , wherein the subject is a human or an animal.

11. The method according to claim 8 , wherein the compound is an antagonist of at least one of lamin A/C, DDX1, hnRNP H2, and hnRNP A2/B1.

12. The method according to claim 8 , wherein the compound is substituted at the R 3 position.

13. The method according to claim 8 , wherein the pharmaceutically acceptable carrier is at least one of a diluent, a binder, a disintegrant, a flavoring, a filler, and a lubricant.

14. The method according to claim 7 , wherein, when the compound is administered to the subject, the compound potentiates basal autophagy and perturbs mitochondrial potential in the metastatic melanoma cells having a mutation in at least one of a BRAF genetic pathway and a NRAS genetic pathway.

15. The method according to claim 9 , wherein, when the compound is administered to the subject, the compound potentiates basal autophagy and perturbs mitochondrial potential in the metastatic melanoma cells having a mutation in at least one of a BRAF genetic pathway and a NRAS genetic pathway.

Assignees

• Univ Nova Southeastern
• Univ Auburn
• Florida Atlantic Univ Board Of Trustees
• Torrey Pines Inst For Molecular Studies
• Florida Atantic Univ Board Of Trustees

Inventors

• Minond Dmitriy
• Fields Gregg B
• Giulianotti Marcello

Classifications

• C07K14/47 Primary

  from mammals · CPC title

• G01N33/564 Primary

  for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9} · CPC title

• C07D403/14 Primary

  containing three or more hetero rings · CPC title

• G01N33/566

  using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds} · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title