# US 2010/0167994 A1 · Targeting of ews-fli1 as anti-tumor therapy

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2010/0167994 A1
- Document ID: US20100167994A1
- Status: Published application
- Kind: A1
- Application number: 12/720,616
- Filed: 2010-03-09
- Published: 2010-07-01
- Earliest claimed: 2006-12-29
- Assignees: Georgetown University
- Inventors: Jeffrey A. Toretsky; Aykut Üren; Milton Lang Brown; Yali Kong
- Web page: https://patentgrep.com/patent/US20100167994A1

## CPC

- C07D 209/38: in positions 2 and 3, e.g. isatin
- A61K 31/404: Indoles, e.g. pindolol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61K 38/00: 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Peptides and compounds are provided that function as EWS-FLI1 protein inhibitors. The peptides and compounds have utility in the treatment of Ewing's sarcoma family of tumors. Also provided are methods of preparing the compounds and assays for identifying inhibitors of EWS-FLI1 protein.

## Claims

### Claim 1

A compound having a formula:
or salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein the salt is a pharmaceutically acceptable salt.

### Claim 3

A method for treating cancer comprising administering an effective amount of a compound having a formula:
or pharmaceutically acceptable salt thereof to a subject in need thereof.

### Claim 4 (depends on 3)

The method of claim 3, wherein the subject is a mammal.

### Claim 5 (depends on 4)

The method of claim 4, wherein the mammal is a human.

### Claim 6 (depends on 3)

The method of claim 3, wherein the cancer is selected from the group consisting of Ewing's sarcoma, clear-cell sarcoma, myxoid liposarcoma, desmoplastic small round-cell tumor, myxoid chondrosarcoma, myxoid liposarcoma, acute myeloid leukemia, congenital fibrosarcoma, prostate cancer, pancreatic cancer, alveolar rhabdomyosarcoma, synovial sarcoma, dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor, and alveolar soft-part sarcoma.

### Claim 7 (depends on 3)

The method of claim 3, wherein the cancer is Ewing's sarcoma.

### Claim 8 (depends on 3)

The method of claim 3, wherein the subject exhibits a gene translocation.

### Claim 9 (depends on 8)

The method of claim 8, wherein the gene translocation encodes a fusion gene selected from the group consisting of EWSR1-FLI1, EWSR1-ERG, EWSR1-ETV1, EWSR1-ETV4, EWSR1-FEV, EWSR1-ATF1, EWSR1-WT1, EWSR1-NR4A3, FUS-DDIT3, EWSR1-DDIT3, PAX3-FOXO1A, PAX7-FOXO1A, SYT-SSX, COL1A1-PDGFB, ETV6-NTRK3, TMP3-ALK, TMP4-ALK, and ASPL-TFE3.

### Claim 10 (depends on 3)

The method of claim 3, further comprising administering an additional therapeutic agent.

### Claim 11 (depends on 10)

The method of claim 10, wherein the additional therapeutic agent is selected from the group consisting of vinca alkaloid, anthracycline, anthracene, epipodophyllo-toxin, actinomyocin D, mithomycin C, mitramycin, methotrexate, docetaxel, etoposide (VP-16), paclitaxel, docetaxel, and adriamycin.

### Claim 12

A pharmaceutical composition comprising a compound having a formula:
or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or diluent.