Cancer treatment with Gö6976 and its related compounds

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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Reexamination Certificate

active

06696478

ABSTRACT:

BACKGROUND OF THE INVENTION
Researchers have recognized that a family of enzymes known as protein kinase C enzymes is associated with a large number of cancers. This family includes at least eleven isoenzymes. A particular member of this family is identified as the protein kinase C alpha enzyme, abbreviated: PKC &agr;.
Researches have reported increases in PKC &agr; activity in human breast tumors (NG et al.,
Science.
283:2085-2089) and significant increases in PKC &agr;: expression in prostate cancers (Cornford et al.,
Am. J. Pathol.
154: 137-144). Researchers have reported that PKC &agr; is required for the metastasis of human melanoma (Dennis et al.,
Cancer Lett.
128:65-70) and that PKC &agr; is related to the progression of brain tumors (Shen et al.,
Mol. Pharmacol.
55:396-402). Recently, Muller et al were granted a patent, U.S. Pat. No. 5,744,460, which discloses a cancer treatment utilizing an antisense oligonuclotide targeted to PKC &agr; combined with a chemotherapeutic agent. U.S. Pat. Nos. 5,882,927 and 5,885,970 issued to Bennett et al also disclose antisense oligonuclotides targeted to PKC.
A chemical known as Gö6976, available from Calbiochem Corp. and Alexis Corp. (both with offices in San Diego, Calif.), is known to be an inhibitor of PKC &agr;. Gö6976 is designated as C24H18N40 and a diagram of the molecule is presented in FIG.
1
. Applicant et al reported in Molecular Cellular Biology, 17:3418-3428 based on a variety of experiments that Gö6976 prevented TPA-induced downregulation of the of PKC &agr; and is a more specific inhibitor for PKC &agr;. What is needed is a better treatment for cancer.
SUMMARY OF THE INVENTION
The present invention provides a chemotheraputic cancer treatment in which Gö6976 or a compound chemically similar to Gö6976 is administered to a mammal for the treatment of the cancer. The chemical compound is targeted to PKC &agr; activity. Experiments have shown Gö6976 and similar compounds to be effective for the treatment of breast cancer, leukemia, lung cancer, bone cancer, skin cancer, prostate cancer, liver cancer, brain tumor, cervical cancer, and cancers located in the digestive tract including gastric cancer and colorectal cancers. These treatments may be accomplished utilizing Gö6976 and compounds similar to it alone or in combination with prior art chemotherapy agents or with radiation therapy. In a preferred embodiment Gö6976 is used for the treatment of cancer as a preventative drug by preventing cancer cell formation. In a preferred embodiment the chemical targeted to PKC &agr; is a chemical having the following structure:
where A, B, C, D, B, F and G are each a modifying chemical or chemical compound.
The modifying chemical or chemical compound may consists of a chemical or chemical compound of the following group of chemicals and chemical compounds: hydrogen, an oxygen, methyl, ethyl, propyl, or isopropyl, carboxymethyl, 2-carboxyethyl, or 3-carboxypropyl, a straight or branched alky of from 1 to a number of carbon atoms, a straight or branched azidoalkyll, carboxyalkyl, amidinothioalkyl, amidinoalkyl, (2-nitroguanidino) alkyl, containing in each case from 1 to a number o carbon atoms, or—(CH2) 2-CO—NX wherein X can be each independently hydrogen, alkyl of from 1 to a number of carbon atoms or benzyl. Preferred chemicals for use in accordance with the present invention are:
A) Gö6976 (trade name): C
24
H
18
N
4
O (formula): 12-(2-Cyanoethyl)-6,7,12,13-tetrahydro- 13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole (chemical name),
B) C-o 002 (trade name): C
23
H
22
N
4
(formula): 12-(3-Aminopropyl)-5,6,7,12,13-pentahydro-indolo[2,3,-a] pyrrolo [3,4-c] carbazole (chemical name)
C) C-o 003 (trade name): C
23
H
24
N
4
Cl
2
(formula): 12-(3-Aminopropyl)-5,6,7,12,13-pentahydro-indolo[2,3,-a] pyrrolo [3,4-c] carbazole hydrochloride (chemical name).


REFERENCES:
patent: 6407058 (2002-06-01), Staddon et al.

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