Procaspase combination therapy for glioblastoma

Patent metadata

Field	Value
Publication number	US-11844798-B2
Application number	US-202017130387-A
Country	US
Kind code	B2
Filing date	Dec 22, 2020
Priority date	Mar 6, 2012
Publication date	Dec 19, 2023
Grant date	Dec 19, 2023

Abstract

The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.

First claim

What is claimed is:

1. A method of treating a bone cancer in a subject in need thereof comprising administering to a subject, concurrently or sequentially, a therapeutically effective amount of each of the compounds temozolomide (TMZ) and first procaspase activating compound (PAC-1)

wherein the bone cancer is osteosarcoma, the TMZ and PAC-1 form a synergistic anticancer combination that is about 20% to about 93% more effective than an additive anticancer effect of TMZ and PAC-1, and osteosarcoma is thereby treated.

2. The method of claim 1 wherein a therapeutically effective concentration of PAC-1 is about 5 μM to about 30 μM, or about 50 mg/kg.

3. The method of claim 2 wherein a therapeutically effective concentration of TMZ is about 250 μM to about 750 μM, or about 50 mg/kg.

4. The method of claim 1 wherein the synergistic anticancer combination is more effective than an additive anticancer effect of TMZ and PAC-1, by about 20.34%, about 26.95%, about 37.72%, about 39.3%, about 39.96%, about 41.06%, about 45.3%, about 55.68%, about 62.57%, about 65.65%, about 69.3%, about 75.36%, about 79.42%, or about 93.49%.

5. The method of claim 1 wherein TMZ and PAC-1 are administered orally, intravenously, or a combination thereof.

6. The method of claim 1 wherein the synergistic anticancer combination is formed in vivo or in vitro.

Assignees

• Univ Illinois
• Vanquish Oncology Inc
• Univ Johns Hopkins

Inventors

• Hergenrother Paul J
• Botham Rachel C
• Fan Timothy M
• Gilbert Mark J
• Handley Michael K
• Joshi Avadhut
• Riggins Gregory J
• Tarasow Theodore M

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K9/4858

  Organic compounds · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title