The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R.sup.1 and R.sup.2 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

##STR00001##

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

Provided is an antibody or a fragment thereof, which can be specifically bound to an S3-4 ring of a voltage sensor paddle of a domain III of voltage-gated sodium channel Nav1.9 α sub-unit, and is able to inactivate a voltage sensor valve to keep sodium ions from entering nerve cells normally. Also provided is an epitope polypeptide specifically bound to the antibody or the fragment thereof, a pharmaceutical composition comprising the antibody or the fragment thereof, and a use of the antibody or the fragment thereof in preparing a drug for treating and diseases related to pains.

Provided is an antibody or a fragment thereof, which can be specifically bound to an S3-4 ring of a voltage sensor paddle of a domain III of voltage-gated sodium channel Nav1.9 α sub-unit, and is able to inactivate a voltage sensor valve to keep sodium ions from entering nerve cells normally. Also provided is an epitope polypeptide specifically bound to the antibody or the fragment thereof, a pharmaceutical composition comprising the antibody or the fragment thereof, and a use of the antibody or the fragment thereof in preparing a drug for treating and diseases related to pains.

Compounds and embodiments of a method for treating and/or preventing autoimmune diseases are disclosed. The method includes administering to a subject having an autoimmune disease, such as an inflammatory bowel disease, a therapeutically effective amount of a compound according to formula I ##STR00001##
wherein X and Y independently are O or NR.sup.1; each R.sup.1 is independently H or C.sub.1-C.sub.6 alkyl; ring A is aryl; each R.sup.2 independently is H, alkyl, alkoxy, amide, cyano, halo, haloalkyl, hydroxyalkyl, heteroalkyl, heterocyclyl, sulfonyl, sulfonamide, or two R.sup.2 groups, taken together with the atom or atoms to which they are attached, combine to form a 4-10 membered ring system; p is 0, 1, 2, 3, or 4; R.sup.3 and R.sup.4 independently are H or C.sub.1-C.sub.6 alkyl; and R.sup.5 is halo, cyano, or C.sub.1-C.sub.6 alkyl.

This disclosure provides compositions and methods for controlling pain. In particular the disclosure provides a method for controlling pain comprising co-administration of an NGF antagonist and a TNFα antagonist. The NGF antagonist and the TNFα antagonist can be separate molecules or part of a multifunctional polypeptide, e.g., a multispecific binding molecule that comprises an NGF antagonist domain and a TNFα antagonist domain. This disclosure also provides multifunctional polypeptides, e.g., multispecific binding molecules, comprising an NGF antagonist domain, and a TNFα antagonist domain. The method provides improved pain control. Administration of an NGF antagonist and a TNFα antagonist as provided herein can control pain in the subject more effectively than an equivalent amount of the NGF antagonist or the TNFα antagonist administered alone.

In a pharmaceutical composition for oral administration comprising 6-(4,4-dimethylcyclohexyl)-4-[(1,1-dioxo-1λ.sup.6-thiomorpholin-4-yl)methyl]-2-methylthieno[2,3-d]pyrimidine or a pharmaceutically acceptable salt thereof, a stable pharmaceutical composition for oral administration with rapid drug dissolution properties is provided. The pharmaceutical composition for oral administration contains a water-swellable substance, which is a polymer compound obtained by condensation polymerization of β-glucose, a polymer compound obtained by condensation polymerization of α-glucose, or a polymer compound having a pyrrolidone functional group.

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

The present invention relates to, inter alia, combinations, methods, compositions, and oral dosage forms of a FAK inhibitor and a MEK inhibitor, for treating abnormal cell growth (e.g., cancer).