# US 8,785,423 B2 · Compositions and methods of inducing endoplasmic reticulum stress response for the treatment of cell proliferative diseases

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- Number: US 8,785,423 B2
- Document ID: US8785423B2
- Status: Granted
- Kind: B2
- Application number: 12/937,900
- Filed: 2009-04-14
- Published: 2011-06-30
- Granted: 2014-07-22
- Earliest claimed: 2008-04-14
- Assignees: University of Maryland, Baltimore
- Applicants: Vincent Njar; Angela Brodie; Robert Bruno
- Inventors: Vincent Njar; Angela Brodie; Robert Bruno
- Web page: https://patentgrep.com/patent/US8785423B2

## CPC

- A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048})
- A61K 33/243: Platinum; Compounds thereof
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- 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 provides methods of inducing cell cycle arrest and/or cell growth inhibition, with the methods comprising administering to the cells an effective dose of the compounds of the present invention.

## Claims

### Claim 1

A method of causing an effect in a prostate cancer cell, wherein the effect is selected from the group consisting of inducing cell cycle arrest in a cell, inducing growth arrest in a cell and inducing apoptosis in a cell, the method comprising coadministering, sequentially or coextensively, to the prostate cancer cell of a patient in need thereof an effective dose of a combination of an amount of a compound of Formula II and
and an amount of thapsigargin, wherein coadministration of the amount of the compound and the amount of thapsigargin to the cell causes said effect in the cell.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cell is a human cell.

### Claim 3 (depends on 1)

The method of claim 1, wherein the effect is inducing apoptosis.

### Claim 4 (depends on 1)

The method of claim 1, wherein the effect is inducing cell cycle arrest.

### Claim 5 (depends on 1)

The method of claim 1, wherein the effect is cell growth arrest.

### Claim 6 (depends on 1)

The method of claim 1, wherein the amount of thapsigargin is 10 nM thapsigargin.

### Claim 7 (depends on 1)

The method of claim 1, wherein the amount of the compound of Formula II is between about 5 μM to 10 μM.

### Claim 8 (depends on 1)

The method of claim 1, wherein the coadministering further comprises administering an amount of an additional agent that induces ER stress, wherein the additional agent that induces ER stress is selected from the group consisting of cisplatin, gentamicin, bortezomib, eeyarestatin, sorafenib, and docosahexaenoic acid (DHA).