A systematic screening has revealed a family of compounds that exhibit inhibitory effects on 12/15-lipoxygenase. Accordingly, the present invention relates to the use of these compounds for the inhibition of 12/15-lipoxygenase and for the treatment of a condition involving 12/15-lipoxygenase. Exemplary conditions include, but are not limited to, stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, and breast cancer.

Provided are methods of treating and/or preventing dermatological disorders. Provided are methods of reducing skin inflammation, reducing pain, and/or reducing itch in a subject in need thereof. The methods may include administering to the subject an effective amount of a TRPV4 inhibitor. Further provided are compositions including a TRPV4 inhibitor compound in combination with a carrier, vehicle, or diluent that is suitable for topical application. Further provided is a transgenic mouse whose genome includes deletions of the Trpv4 gene in keratinocytes of the epidermis, wherein said transgenic mouse is a knockout for the Trpv4 gene in keratinocytes of the epidermis following keratinocyte-specific activation and expression of a site-specific recombination enzyme.

Provided are methods of treating and/or preventing dermatological disorders. Provided are methods of reducing skin inflammation, reducing pain, and/or reducing itch in a subject in need thereof. The methods may include administering to the subject an effective amount of a TRPV4 inhibitor. Further provided are compositions including a TRPV4 inhibitor compound in combination with a carrier, vehicle, or diluent that is suitable for topical application. Further provided is a transgenic mouse whose genome includes deletions of the Trpv4 gene in keratinocytes of the epidermis, wherein said transgenic mouse is a knockout for the Trpv4 gene in keratinocytes of the epidermis following keratinocyte-specific activation and expression of a site-specific recombination enzyme.

Disclosed herein are compounds of Formula (I), methods of synthesizing compounds of Formula (I), and methods of using compounds of Formula (I) as an analgesic.

The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent. ##STR00001##

The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent. ##STR00001##

The invention relates to new compounds of formula (I)

##STR00001##

with low cytotoxicity for blocking the ubiquitination-proteasome system in diseases. Accordingly, these compounds can be used in treatment of disorders including, but not limited to, cancers.

The invention relates to new compounds of formula (I)

##STR00001##

with low cytotoxicity for blocking the ubiquitination-proteasome system in diseases. Accordingly, these compounds can be used in treatment of disorders including, but not limited to, cancers.

The present invention features compounds useful in the inhibition of the secretion of proteins. The compounds of the invention can be used in methods for treating diseases associated with protein secretion, and in methods for inhibiting protein secretion.

The present invention features compounds useful in the inhibition of the secretion of proteins. The compounds of the invention can be used in methods for treating diseases associated with protein secretion, and in methods for inhibiting protein secretion.