# US 11,993,775 B2 · Ubiquitin-specific peptidase 24 inhibitor, medicinal composition and method of delaying or reversing multidrug resistance in cancers using the same

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- Number: US 11,993,775 B2
- Document ID: US11993775B2
- Status: Granted
- Kind: B2
- Application number: 16/939,543
- Filed: 2020-07-27
- Published: 2022-01-27
- Granted: 2024-05-28
- Earliest claimed: 2020-07-27
- Assignees: National Cheng Kung University
- Applicants: National Cheng Kung University
- Inventors: Chien-Chung Hung
- Web page: https://patentgrep.com/patent/US11993775B2

## CPC

- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- A61K 31/5415: ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
- A61P 35/00: Antineoplastic agents
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/31: Combination therapy
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

## Abstract

The present invention relates to a ubiquitin-specific peptidase 24 inhibitor, a medicinal composition and a method of delaying or reversing multidrug resistance in cancers using the same. The USP24 inhibitor, which includes a shUSP24 RNA and/or a carbonyl substituted phenyl compound, can serve as a chemosensitizing agent for inhibiting the drug pump out, cancer stemness and genomic instability of cancer cells, thereby being applied to a medicinal composition and a method for delaying or reversing multidrug resistance in cancers.

## Claims

### Claim 1

A method for specifically inhibiting ubiquitin-specific peptidase 24 (USP24) in cancer cells, comprising:
administering a medicinal composition to the cancer cells which are suspicious of a cancerous or undifferentiated phenotype expressing multidrug resistance, wherein the medicinal composition comprises:
a chemotherapeutic drug; and
a chemosensitizing agent comprising a ubiquitin-specific peptidase 24 (USP24) inhibitor composition, wherein the USP24 inhibitor composition comprises a short interfering nucleic acid (siNA) and a carbonyl substituted phenyl compound, the siNA is a short interfering ribonucleic acid (siRNA), the siRNA is a short-hairpin USP24 (shUSP24) RNA having a sequence listed as SEQ ID NO:1, the carbonyl substituted phenyl compound has a structure as formula (I-3):

### Claim 2 (depends on 1)

The method of claim 1, wherein the siRNA is a double-stranded USP24 RNA.

### Claim 3 (depends on 1)

The method of claim 1, wherein the siRNA is an isolated ribonucleic acid sequence or a viral siRNA construct.

### Claim 4 (depends on 3)

The method of claim 3, wherein the viral siRNA construct is a lentiviral siRNA construct, and a value of multiplicity of infection (m.o.i.) of the lentiviral siRNA construct is 2.5 to 10.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cancer cells comprise a lung cancer cell, a nasopharyngeal carcinoma cell, a brain cancer cell and a colorectal carcinoma cell.

### Claim 6

A method for delaying or reversing multidrug resistance in cancers, comprising:
administering a medicinal composition to cancer cells which are suspicious of a cancerous or undifferentiated phenotype expressing multidrug resistance, wherein the medicinal composition comprises:
a chemotherapeutic drug; and
a chemosensitizing agent comprising a ubiquitin-specific peptidase 24 (USP24) inhibitor composition, wherein the USP24 inhibitor composition comprises a short interfering nucleic acid (siNA) and a carbonyl substituted phenyl compound, and the siNA is a short interfering ribonucleic acid (siRNA), the siRNA is a short-hairpin USP24 (shUSP24) RNA having a sequence listed as SEQ ID NO:1, and the carbonyl substituted phenyl compound has a structure as formula (I-3):

### Claim 7 (depends on 6)

The method of claim 6, wherein the siRNA is an isolated ribonucleic acid sequence or a viral siRNA construct.

### Claim 8 (depends on 7)

The method of claim 7, wherein the viral siRNA construct is a lentiviral siRNA construct, and a value of m.o.i. of the lentiviral siRNA construct is 2.5 to 10.

### Claim 9 (depends on 6)

The method of claim 6, wherein the cancer cells comprise a lung cancer cell, a nasopharyngeal carcinoma cell, a brain cancer cell and a colorectal carcinoma cell.