Procaspase 3 activation by combination therapy

Patent metadata

Field	Value
Publication number	US-2021128551-A1
Application number	US-202117144926-A
Country	US
Kind code	A1
Filing date	Jan 8, 2021
Priority date	Mar 6, 2012
Publication date	May 6, 2021
Grant date	—

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

1 . A composition comprising the compound PAC-1:

and a second active agent, wherein the second active agent is synergistic with PAC-1 in the treatment of cancer.

2 . The composition of claim 1 wherein the second active agent is sunitinib.

3 . A method of treating cancer comprising administering to a subject in need thereof an effective amount of PAC-1:

and an effective amount of a second active agent, wherein the second active agent is synergistic with PAC-1 in the treatment of the cancer.

4 . The method of claim 3 wherein the second active agent is sunitinib.

5 . The method of claim 4 wherein the PAC-1 is administered orally.

6 . The method of claim 4 wherein the sunitinib is administered orally.

7 . The method of claim 4 wherein the cancer is a renal cell carcinoma or a gastrointestinal stromal tumor.

8 . A method of treating cancer comprising administering to a subject in need thereof an effective amount of SPAC-1:

and an effective amount of a second active agent, wherein the second active agent is synergistic with PAC-1 in the treatment of the lung cancer.

9 . The method of claim 8 wherein the second active agent is sunitinib.

10 . The method of claim 9 wherein the cancer is a renal cell carcinoma or a gastrointestinal stromal tumor.

Assignees

• Univ Illinois
• Vanquish Oncology Inc

Inventors

• Hergenrother Paul J
• Botham Rachel C
• Fan Timothy M
• Gilbert Mark J
• Handley Michael K
• Roth Howard S
• Tarasow Theodore M

Classifications

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• A61K47/40

  Cyclodextrins; Derivatives thereof · CPC title

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61K31/4965

  Non-condensed pyrazines · CPC title

• A61K31/495 Primary

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title