Summary:

A new direction for both basic and clinical cancer research involves the study of apoptosis, a type of programmed cell death. While traditional cancer research has focused on why cancer cells seemingly proliferate in an uncontrollable fashion, new research has determined that the problem with cancer cells may instead be that the natural internal maturation pathways common to normal cells are in someway suppressed in cancerous cells. Therefore, cancer cells are able to survive longer than normal cells. Based on these new findings, the identification and development of new compounds which will selectively stimulate apoptosis offers a significant new approach to combating cancer.

Ohio State researchers have isolated compounds useful for inducing apoptosis in proliferative cells, including but not limited to cancer cells. The compounds are further useful for treating, inhibiting, and delaying the onset of cancer in mammals, and especially in humans. Cancers that these compounds work particularly well against include leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, bladder cancer, lymphoma, and breast cancer. Surprisingly, the compounds of the present invention are able to induce apoptosis in cancer cells independent of the level of Bcl-2 expression and p53 functional status, which means that the inventive compounds are potent even against cancers that are androgen-independent, such as hormone-refractory prostate cancer.

Potential Applications:

Treatment of leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, bladder cancer, lymphoma, and breast cancer.

Advantages:

Can treat cancer cells that are androgen-independent or are resistant to current treatment.

Summary:

Protein tyrosine phosphatases (PTPs) are a large family of enzymes that remove a phosphoryl group from phosphotyrosyl (pY) proteins. A number of PTPs have been shown as viable targets for treatment of human diseases and conditions. For example, PTP1B inhibitors are expected to be effective therapeutics for type II diabetes and obesity.

SH2 domains are small modular domains found in a large number of signaling proteins. Their function is to bind to pY-containing proteins and promote protein-protein interactions. Inhibitors against SH2 domains have potential applications in treating cancer, osteoporosis, and inflammation, etc.

Because both proteins bind pY proteins as natural ligands, other investigators have developed a variety of pY mimetics which closely mimic the structure of pY. While some of them bind to PTPs and SH2 domains with high affinity, they are not membrane permeable due to their negative charge(s). In this invention, we have discovered a class of neutral molecules that bind reversibly to both PTPs and SH2 domains with high affinity and selectivity. Because the pY mimetic in this invention is neutral, inhibitors containing this core should have good membrane permeability and therefore offer a good lead for developing potent, selective PTP and SH2 inhibitors for therapeutic use.

Potential Applications:

Treatment of type II diabetes and obesity

Advantages:

• More selective inhibitor
• More potent

Summary:

The vitamin A metabolite, retinoic acid, appears to be necessary for the maintenance of normal epithelial tissue differentiation. As a result, this compound has been proposed as a cancer chemopreventive agent. Unfortunately, retinoic acid and its analogs (retinoids) are relatively toxic. This invention involves the synthesis of retinoid analogs with increased potency and/or reduced toxicity for application as cancer preventive agents.

Potential Applications:

Chemopreventive agent for breast cancer

Advantages:

• Less toxic than the original compound
• High potency for cancer treatment

Summary:

A new direction for both basic and clinical cancer research involves the study of apoptosis, a type of programmed cell death. While traditional cancer research has focused on why cancer cells seemingly proliferate in an uncontrollable fashion, new research has determined that the problem with cancer cells may instead be that the natural internal maturation pathways common to normal cells are in someway suppressed in cancerous cells. Therefore, cancer cells are able to survive longer than normal cells. Based on these new findings, the identification and development of new compounds which will selectively stimulate apoptosis offers a significant new approach to combating cancer.

We have isolated and synthesized a novel compound which has been demonstrated to selectively kill leukemia cells while sparing the harmful side effects of current chemotherapeutic modalities. In preliminary in vitro studies, this compound killed human leukemia cells while fibroblastoid cell lines were not affected. The present invention provides a new branched apogenic peptide for inducing apoptosis in non-quiescent cells. The branched apogenic peptide comprises an amino acid core of at least three and preferably seven amino acids. Preferable the core amino acids are lysine molecules. Attached to the core are at least four, preferably eight identical peptide chains comprising the following amino acids in the following order: Z X X Z wherein: Z is arginine, lysine, or any synthetic positively charged amino acid; and X is any amino acid. The invention also relates to a method of inducing apoptosis.

Potential Applications:

Cancer treatment

Advantages:

Selective destruction of cancerous cells without harming normal cells

Summary:

Researchers at the Ohio State University have developed methods for inhibiting and/or reversing tau filament formation or polymerization to treat certain neurological diseases. Alzheimer’s disease is a progressive neurodegenerative disease characterized in part by a constellation of intracellular neurofibrillary lesions termed neurofibrillary tangles, neuritic plaques, ad neuropil threads. Each manifestation of neurofibrillary pathology is comprised of tau protein polymerized into filaments. Neurofibrillary lesions appear with a stereotypic spatial distribution and correlate with both neuronal cell loss and cognitive decline; they are also useful markers of degeneration in alzheimer’s and other dementias.

Potential Applications:

Treatment and detection of neurodegenerative diseases like alzheimer’s.

Advantages:

These methods have the ability to inhibit and/or reverse the effects of alzheimer’s disease.

Summary:

Researchers at The Ohio State University have discovered an anti-cancer treatment which has an improved stability and does not produce acrolein. The invention includes dichlorodiethyl phosphoramide drugs including, for example, the cyclohexylamine salt phosphoramide mustard and isophosphoramide mustard and mixtures thereof, which have been entrapped by liposomes. Preferably the liposomes contain sphingomyelin and cholesterol.

Potential Applications:

Treatment of various types of cancer.

Advantages:

Less toxic than previous treatments because it does not produce acrolein and other harmful byproducts.