| Title: |
Peptide and small molecule agonists of EphA and their uses |
| Patent Number: |
9,415,086 |
| Publication Date: |
August 16, 2016 |
| Appl. No: |
13/461098 |
| Application Filed: |
May 01, 2012 |
| Abstract: |
Methods and compositions for activating an EphA receptor can be used for identifying therapeutic agents for cancer. |
| Inventors: |
Wang, Bingchen (Strongsville, OH, US); Myshkin, Eugene (Cleveland, OH, US); Miao, Hui (Rocky River, OH, US) |
| Claim: |
1. A method of inhibiting proliferation of cancer cells that overexpress EphA2 receptor proteins comprising: administering to the cancer cells of an individual an amount of an agonist of EphA2 receptor protein effective to inhibit the cancer cells' growth, migration, and/or proliferation, the agonist comprising a small molecule, the small molecule having a general formula A-L-B, wherein A and B are independently selected from aryl, and L is selected from C 1-12 alkyl and —C 1-6 alkyl-amino-C 1-6 alkyl- and a molecular weight of about 50 daltons to about 2500 daltons, and stimulating phosphorylation of tyrosine of EphA2 in an in vitro assay, wherein the cancer cells comprise lung cancer cells. |
| Claim: |
2. The method of claim 1 , wherein L is 7 to 10 bonds in length. |
| Claim: |
3. The method of claim 1 , wherein L is —C 1-6 alkyl-amino-C 1-6 alkyl-. |
| Claim: |
4. The method of claim 1 , the small molecule having the general formula: [chemical expression included] wherein R 8 is selected from H, C 1-6 alkyl, C 1-6 aralkyl, C 1-6 alkanoyl, aryl, heterocyclyl, C 1-6 heterocyclylalkyl, C 1-6 carbocyclylalkyl, and carbocyclyl, or two occurrences of R 8 together are C 1-6 alkyl, thereby forming a ring; R 9 and R 19 are independently selected from Hand C 1-4 alkyl; R 11 is selected from H, OH, C 1-6 alkoxy, and C 1-6 alkanoyl; X 1 is NH; m 1 is an integer from 1 to 2; and n 1 is an integer from 1 to 3. |
| Claim: |
5. The method of claim 1 , the small molecule being selected from the group consisting of labetalol and dobutamine. |
| Claim: |
6. A method of treating cancer in an individual comprising: administering to cancer cells of the individual an amount of an agonist of EphA2 receptor protein effective to inhibit the cancer cells' growth, migration, and/or proliferation, the agonist comprising a small molecule, the small molecule having a general formula A-L-B, wherein A and B are independently selected from aryl, and L is selected from C 1-12 alkyl and —C 1-6 alkyl-amino-C 1-6 alkyl- and a molecular weight of about 50 daltons to about 2500 daltons, and stimulating phosphorylation of tyrosine of EphA2 in an in vitro assay, wherein the cancer cells comprise lung cancer cells. |
| Claim: |
7. The method of claim 6 , wherein L is 7 to 10 bonds in length. |
| Claim: |
8. The method of claim 6 , the —C 1-6 alkyl-amino-C 1-6 alkyl-. |
| Claim: |
9. The method of claim 6 , the small molecule having the general formula: [chemical expression included] wherein R 8 is selected from H, C 1-6 alkyl, C 1-6 aralkyl, C 1-6 alkanoyl, aryl, heterocyclyl, C 1-6 heterocyclylalkyl, C 1-6 carbocyclylalkyl, and carbocyclyl, or two occurrences of R 8 together are C 1-6 alkyl, thereby forming a ring; R 9 and R 19 are independently selected from Hand C 1-4 alkyl; R 11 is selected from H, OH, C 1-6 alkoxy, and C 1-6 alkanoyl; X 1 is NH; m 1 is an integer from 1 to 2; and n 1 is an integer from 1 to 3. |
| Claim: |
10. The method of claim 6 , the small molecule being selected from the group consisting of labetalol and dobutamine. |
| Patent References Cited: |
2337690 February 2000 |
| Primary Examiner: |
Hui, San-Ming |
| Attorney, Agent or Firm: |
Tarolli, Sundheim, Covell & Tummino LLP |
| Accession Number: |
edspgr.09415086 |
| Database: |
USPTO Patent Grants |
