Inhibiting FAK-AKT interaction to inhibit metastasis

Patent metadata

Field	Value
Publication number	US-11452764-B2
Application number	US-201816632748-A
Country	US
Kind code	B2
Filing date	Jul 19, 2018
Priority date	Jul 21, 2017
Publication date	Sep 27, 2022
Grant date	Sep 27, 2022

Abstract

Methods and compositions are described herein that inhibit FAK/ATK interactions. Such methods and compositions are useful for inhibiting cell adhesion and cancer metastasis.

First claim

What is claimed:

1. A method of reducing metastasis of cancer cells in a mammal comprising administering one or more inhibitors of FAK/Akt1 to a mammal in an amount sufficient to reduce metastasis of cancer cells in the mammal, wherein the inhibitor is:
one or more compounds with the following structure:

wherein:
Ring A and Ring C independently are each an aryl ring;
Ring B is a cycloalkyl ring;
R 1 is a lower alkyl or lower alkoxy;
X is a C 1 to C 4 alkyl linker comprising a carbonyl, a carboxylate, an amide, a carboxylate(amino), or an aminocarboxylate group or a ═N—O—SO 2 — linker; and
R 2 and R 3 are independently each a carboxylate, an amide, or a nitro group.

2. The method of claim 1 , wherein the compound is:

3. The method of claim 1 wherein each aryl ring is a cyclic aromatic hydrocarbon that does not contain heteroatoms.

4. The method of claim 1 wherein the alkyl groups each have from 1 to about 20 carbon atoms.

5. The method of claim 1 the Ring B group is a C 1 to C 8 cycloalkyl, or a C 1 to C 6 cycloalkyl.

6. The method of claim 1 wherein, the X group is a three to four atom linker, where atoms can include one or more carbon, oxygen, and nitrogen atoms, and where the carbon and/or nitrogen atoms can be substituted with an alkyl or an oxy group.

7. The method of claim 1 wherein X is a C 1 to C 4 alkyl linker comprising a carbonyl, a carboxylate, an amide, a carboxylate(amino), or an aminocarboxylate group.

8. The method of claim 1 wherein, the X group is a three-atom linker, with one carbon, one oxygen, and one nitrogen atom.

9. The method of claim 1 wherein, the X group comprises a carbonyl.

10. The method of claim 1 wherein, the R 2 and R 3 groups are independently a carboxylate, or a nitro group.

11. The method of claim 1 wherein, the inhibitor is the compound shown below:

Assignees

• Univ Michigan State
• Univ Of North Dakota

Inventors

• Basson Marc D
• Kuhn Leslie A
• Raschka Sebastian

Classifications

• C07K7/06

  having 5 to 11 amino acids · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12Y207/10002

  Non-specific protein-tyrosine kinase (2.7.10.2), i.e. spleen tyrosine kinase · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K14/4703

  Inhibitors; Suppressors · CPC title