The present invention provides a compound of Formula I:

##STR00001##

useful for treating chronic kidney disease and diabetic kidney disease.

Pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the serotonin 5HT.sub.2A receptor. Formula (Ia). Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or symptoms thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de Ia Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorders, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT.sub.2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together. ##STR00001##

A method of reducing blood glucose in a subject has been developed. In preferred embodiments, the method involves administering to the subject a specific activator of endogenous mitogen-activated protein kinase kinase 6 (MKK3), mitogen-activated protein kinase kinase 6 (MKK4), mitogen-activated protein kinase kinase 6 (MKK6), p38 mitogen-activated protein kinase (p38MAPK), mitogen-activated kinase-activated protein kinase 2 (MK2), or a combination thereof, in an effective amount to reduce blood glucose in a subject. In other embodiments, the method involves administering to the subject a specific activator to increase X-box binding protein 1 (XBP1) phosphorylation on Thr48 and Ser61 in an effective amount to reduce blood glucose in the subject. Methods of identifying agents for reducing blood glucose in a subject are also provided.

Methods for treating type one diabetes mellitus in a subject in need thereof and pharmaceutical compositions for the treatment of type one diabetes mellitus are disclosed, including combination therapies with insulin. The methods include administering an effective amount of apolipoprotein A-IV to the subject having type I diabetes. The pharmaceutical composition includes apolipoprotein A-IV formulated for administration to a subject for the treatment of type one diabetes mellitus.

Methods for treating type one diabetes mellitus in a subject in need thereof and pharmaceutical compositions for the treatment of type one diabetes mellitus are disclosed, including combination therapies with insulin. The methods include administering an effective amount of apolipoprotein A-IV to the subject having type I diabetes. The pharmaceutical composition includes apolipoprotein A-IV formulated for administration to a subject for the treatment of type one diabetes mellitus.

A method of ameliorating symptoms of uremia includes administering a therapeutic agent including beraprost or each isomer constituting beraprost, or a salt thereof as an effective ingredient to an animal belonging to the Family Canidae, wherein an effective dosage is a dosage that does not significantly lower blood pressure.

Provided herein are methods of reducing the incident of disease flares in a subject in need thereof.

Provided herein are methods of reducing the incident of disease flares in a subject in need thereof.

The present invention relates to compounds of formula I ##STR00001##
wherein A.sub.1, A.sub.2, A.sub.3, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, L, Ar and Q are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.

The present invention relates to compounds of formula I ##STR00001##
wherein A.sub.1, A.sub.2, A.sub.3, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, L, Ar and Q are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.