The present invention relates to a compound inhibiting HF-1 activity, a preparation method of the same, and a pharmaceutical composition comprising the same as an active ingredient. The compound of the present invention demonstrates anticancer activity not by non-selective cytotoxicity but by inhibiting the activity of HIF-1, the transcription factor playing an important role in cancer cell growth and metastasis.

Accordingly, the compound or the pharmaceutically acceptable salt thereof according to the present invention inhibits HIF-1 activity, and therefore can be used as a therapeutic agent for solid tumors such as colon cancer, liver cancer, stomach cancer and breast cancer. In addition, the compound or the pharmaceutically acceptable salt thereof according to the present invention can be used as an active ingredient for a therapeutic agent for diabetic retinopathy or arthritis which may become worse when hypoxia-induced VEGF expression by HIF-1 increases.

The present invention relates to a compound inhibiting HF-1 activity, a preparation method of the same, and a pharmaceutical composition comprising the same as an active ingredient. The compound of the present invention demonstrates anticancer activity not by non-selective cytotoxicity but by inhibiting the activity of HIF-1, the transcription factor playing an important role in cancer cell growth and metastasis.

Accordingly, the compound or the pharmaceutically acceptable salt thereof according to the present invention inhibits HIF-1 activity, and therefore can be used as a therapeutic agent for solid tumors such as colon cancer, liver cancer, stomach cancer and breast cancer. In addition, the compound or the pharmaceutically acceptable salt thereof according to the present invention can be used as an active ingredient for a therapeutic agent for diabetic retinopathy or arthritis which may become worse when hypoxia-induced VEGF expression by HIF-1 increases.

The inventors have unexpectedly discovered that shock and/or potential multi-organ failure due to shock can be effectively treated by administration of liquid high-dose protease inhibitor formulations to a location upstream of where pancreatic proteases are introduced into the gastrointestinal tract. Most preferably, administration is directly to the stomach, for example, via nasogastric tube under a protocol effective to treat shock by such administration without the need of providing significant quantities of the protease inhibitor to the jejunum and/or ileum.

The inventors have unexpectedly discovered that shock and/or potential multi-organ failure due to shock can be effectively treated by administration of liquid high-dose protease inhibitor formulations to a location upstream of where pancreatic proteases are introduced into the gastrointestinal tract. Most preferably, administration is directly to the stomach, for example, via nasogastric tube under a protocol effective to treat shock by such administration without the need of providing significant quantities of the protease inhibitor to the jejunum and/or ileum.

The present disclosure provides a compound of Formula (I); ##STR00001## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 and R.sup.2 are defined herein. The disclosure also relates to a method for manufacturing the compounds of the disclosure, and its therapeutic uses. The present disclosure further provides pharmaceutical composition of the compounds of the disclosure and a combination of pharmacologically active agents and a compound of the disclosure.

A use of Gemifibrozil and a pharmaceutically acceptable salt, ester, or stereoisomer thereof in the preparation of a medicament for the treatment and/or prevention of a neurodegenerative disease. The neurodegenerative disease is selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis. Further provided is a pharmaceutical composition for treating and/or preventing a neurodegenerative disease, wherein the pharmaceutical composition comprises Gemifibrozil, or a pharmaceutically acceptable salt, ester, or stereoisomer thereof, and, preferably, the pharmaceutical composition further comprises one or a plurality of pharmaceutically acceptable carriers. Further provided is a use of the pharmaceutical composition comprising Gemifibrozil, or a pharmaceutically acceptable salt, ester, or stereoisomer thereof in the preparation of a medicament for the treatment and/or prevention of a neurodegenerative disease.

A use of Gemifibrozil and a pharmaceutically acceptable salt, ester, or stereoisomer thereof in the preparation of a medicament for the treatment and/or prevention of a neurodegenerative disease. The neurodegenerative disease is selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis. Further provided is a pharmaceutical composition for treating and/or preventing a neurodegenerative disease, wherein the pharmaceutical composition comprises Gemifibrozil, or a pharmaceutically acceptable salt, ester, or stereoisomer thereof, and, preferably, the pharmaceutical composition further comprises one or a plurality of pharmaceutically acceptable carriers. Further provided is a use of the pharmaceutical composition comprising Gemifibrozil, or a pharmaceutically acceptable salt, ester, or stereoisomer thereof in the preparation of a medicament for the treatment and/or prevention of a neurodegenerative disease.

Methods and compositions are described herein that inhibit FAK/ATK interactions. Such methods and compositions are useful for inhibiting cell adhesion and cancer metastasis.

Methods and compositions are described herein that inhibit FAK/ATK interactions. Such methods and compositions are useful for inhibiting cell adhesion and cancer metastasis.

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.