# US 11,299,509 B2 · Trigger-activatable sugar conjugates for cancer-selective labeling and targeting

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- Number: US 11,299,509 B2
- Document ID: US11299509B2
- Status: Granted
- Kind: B2
- Application number: 16/485,090
- Filed: 2018-02-12
- Published: 2019-12-05
- Granted: 2022-04-12
- Earliest claimed: 2017-02-10
- Assignees: The Board of Trustees of the University of Illinois
- Applicants: The Board of Trustees of the University of Illinois
- Inventors: Jianjun Cheng; Kaimin Cai; Jin Yu
- Web page: https://patentgrep.com/patent/US11299509B2

## CPC

- C07H 15/18: Acyclic radicals, substituted by carbocyclic rings
- C07H 15/26: Acyclic or carbocyclic radicals, substituted by hetero rings
- A61K 31/5365: ortho- or peri-condensed with heterocyclic ring systems
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- A61K 47/555: {pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells}
- A61P 35/00: Antineoplastic agents
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- 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

Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl-drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity. Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds.

## Claims

### Claim 1

A compound represented by formula (XI) or a pharmaceutically acceptable salt thereof:
K-Pol-L2-D (XI);
wherein:
K is
Pol is a polyalkylene glycol;
L2 is a trigger-responsive moiety comprising a disulfide bond; and
D is
wherein the compound comprises a disulfide moiety.

### Claim 2 (depends on 1)

The compound of claim 1 wherein Pol is:
wherein n is 0-5000.

### Claim 3 (depends on 1)

The compound of claim 1 wherein one end of the disulfide bond is a bond to the sulfur atom of the moiety:
wherein
R6 is H, tri((C1-C6)alkyl)silyl, or —C(O)((C1-C6)alkyl); or
n is 1 or 2.

### Claim 4 (depends on 1)

The compound of claim 1 wherein one end of the disulfide bond is a bond via a sulfur atom to the moiety:
wherein R6 is H, tri((C1-C6)alkyl)silyl, —C(O)((C1-C6)alkyl), or —(C1-C6)alkyl.

### Claim 5 (depends on 1)

The compound of claim 1 wherein one end of the disulfide bond is a bond via a sulfur atom to the moiety:
wherein n is 1 or 2.

### Claim 6 (depends on 1)

The compound of claim 1 wherein the compound comprises:
wherein n is 0-5000.

### Claim 7 (depends on 1)

A pharmaceutical composition, comprising a compound of claim 1, and a pharmaceutically acceptable excipient or carrier.

### Claim 8 (depends on 7)

The pharmaceutical composition of claim 7 wherein the compound is DM1-SS-PEG-DBCO and n is an integer from 1 to 5000.

### Claim 9 (depends on 1)

A method of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1, wherein the compound inhibits proliferation of breast cancer cells.

### Claim 10 (depends on 9)

The method of claim 9 wherein the compound is DM1-SS-PEG-DBCO and n is an integer from 1 to 5000.

### Claim 11

The compound DM1-MAL-PEG-DBCO:
wherein n is an integer from 1 to 5000.

### Claim 12 (depends on 11)

The compound of claim 11 wherein n is an integer from 4 to 30.

### Claim 13 (depends on 11)

A pharmaceutical composition comprising the compound of claim 11 and a pharmaceutically acceptable excipient or carrier.

### Claim 14 (depends on 11)

A method of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 11, wherein the compound inhibits proliferation of breast cancer cells.

### Claim 15

The compound DM1-SS-PEG-DBCO:
wherein n is an integer from 1 to 5000.

### Claim 16 (depends on 15)

The compound of claim 15 wherein n is an integer from 4 to 30.