# US 11,110,080 B2 · Small molecule inhibitors of bacterial efflux pumps and methods of using same

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- Number: US 11,110,080 B2
- Document ID: US11110080B2
- Status: Granted
- Kind: B2
- Application number: 16/497,315
- Filed: 2018-03-27
- Published: 2020-01-23
- Granted: 2021-09-07
- Earliest claimed: 2017-03-27
- Assignees: The Regents of the University of Colorado, a body corporate
- Applicants: The Regents of the University of Colorado, a body Corporate
- Inventors: Abigail L. Reens; Amy L. Crooks; Corrella S. Detweiler
- Web page: https://patentgrep.com/patent/US11110080B2

## CPC

- A61K 31/426: 1,3-Thiazoles
- A61P 31/04: Antibacterial agents
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/65: Tetracyclines
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12Q 1/18: Testing for antimicrobial activity of a material
- G01N 33/502: {for testing non-proliferative effects}
- G01N 33/5055: {involving macrophages}
- G01N 2333/255: Salmonella (G)
- 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
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

An empirical Screen for Anti-infectives using Fluorescence microscopy of IntracellulaR Enterobacteriaceae (SAFIRE) was developed. Using this methodology, a library of small molecules and identified antimicrobials that are cell permeable and non-host-toxic were screened. Inhibitors of bacterial efflux pumps were identified as being implicated in antibiotic resistance and are attractive therapeutic targets for antimicrobials.

## Claims

### Claim 1

A pharmaceutical composition comprising an effective amount of an efflux pump modulator compound and a pharmaceutically acceptable carrier, wherein the efflux pump modulatory compound has one of the structure:
(EPM30)
(EPM35), or
(EPM43).

### Claim 2

A method of treating a bacterial pathogen in a subject, the method comprising administering to the subject a therapeutically effective amount of an efflux pump modulator (EPM) compound, wherein the EPM is

### Claim 3 (depends on 2)

The method of claim 2, further comprising administering an antimicrobial peptide or an antibiotic.

### Claim 4 (depends on 3)

The method of claim 3, wherein the antibiotic comprises tetracycline.

### Claim 5 (depends on 3)

The method of claim 3, wherein the antimicrobial peptide comprises polymyxin B.

### Claim 6 (depends on 2)

The method of claim 2, wherein the EPM compound comprises EPM30.

### Claim 7 (depends on 2)

The method of claim 2, wherein the EPM compound comprises EPM35.

### Claim 8 (depends on 2)

The method of claim 2, wherein the EPM compound comprises EPM43.

### Claim 9 (depends on 2)

The method of claim 2, wherein the bacterial pathogen comprises one or more of a Salmonella sp., K. pneumoniae, Enterobacter cloacae, or E. coli.

### Claim 10 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier is present an amount ranging from 1-99%.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is an aqueous composition which is formulated at a pharmaceutically acceptable pH and tonicity.