The present invention discloses compounds according to Formula I:

##STR00001##

Wherein R.sup.1a, R.sup.1b, R.sup.2, R.sup.4, R.sup.5, R.sup.6a, R.sup.6b, R.sup.7, R.sup.8, W, X, Cy, and the subscript a are as defined herein.

The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.

The invention relates to compounds of Formula (I) as described herein, useful as histone deacetylase 6 (HDAC6) inhibitors. The invention also relates to pharmaceutical compositions comprising these compounds and to their use in therapy.

The present application provides improved compositions, methods, kits and dosing regimens for the use of heterocyclic compounds and pharmaceutically acceptable salts, prodrugs, solvates, hydrates, or stereoisomers thereof. These compositions, methods, kits and dosing regimens are useful for modulating ERK1/2. By administering to a subject in need a therapeutically effective amount of one or more of the compounds of Formulae (I-III) or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, or stereoisomer thereof, or compositions of these, wherein X, Y, Z, J, M, and R.sup.1 to R.sup.8 are defined herein, these compounds and methods are effective in treating conditions associated with dysregulation of the RAS/RAF/MEK/ERK pathway or which are treatable by inhibiting Erk 1/2. A variety of conditions can be treated using these compounds and methods and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer.

##STR00001##

The present disclosure is directed to use of MrgprX2 antagonists in the treatment of inflammatory disorders, e.g., inflammatory disorders of the skin. This invention is also directed to pharmaceutical compositions comprising a MrgprX2 antagonist and a pharmaceutically or orally acceptable carrier for administration.

The present disclosure is directed to use of MrgprX2 antagonists in the treatment of inflammatory disorders, e.g., inflammatory disorders of the skin. This invention is also directed to pharmaceutical compositions comprising a MrgprX2 antagonist and a pharmaceutically or orally acceptable carrier for administration.

The present disclosure provides methods of treating cancer with non-competitive, agonist anti-OX40 antibodies and antigen-binding fragments thereof that bind to human OX40 (ACT35, CD134, or TNFRSF4), in combination with a multi-kinase inhibitor.

The present disclosure provides methods of treating cancer with non-competitive, agonist anti-OX40 antibodies and antigen-binding fragments thereof that bind to human OX40 (ACT35, CD134, or TNFRSF4), in combination with a multi-kinase inhibitor.

The present disclosure provides methods of treating cancer with non-competitive, agonist anti-OX40 antibodies and antigen-binding fragments thereof that bind to human OX40 (ACT35, CD134, or TNFRSF4), in combination with a multi-kinase inhibitor.

Methods for preventing or treating diastolic dysfunction in an individual comprising administering to an individual in need of said prevention or treatment a therapeutically effective amount of a mGluR5 negative allosteric modulator, compositions comprising a mGluR5 negative allosteric modulator for use in treatment of diastolic dysfunction and pharmaceutical compositions comprising same.

Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula

##STR00001##

inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.