Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.

An abstract heading is required. Please delete this heading section if it is not applicable to your application. For more information regarding the headings of the abstract, please see MPEP 608.01(b).

An abstract heading is required. Please delete this heading section if it is not applicable to your application. For more information regarding the headings of the abstract, please see MPEP 608.01(b).

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The present disclosure includes, among other things, CFTR modulators, pharmaceutical compositions, and methods of making and using the same.

The present disclosure includes, among other things, CFTR modulators, pharmaceutical compositions, and methods of making and using the same.

The invention relates to selected macrocyclic compounds, and their use in the treatment or prevention of diseases and disorders. In particular, though not exclusively, the invention relates to the use of selected macrocyclic compounds in the treatment or prevention of diseases that are caused by (1) cell death due to various causes and (2) inflammation. Such diseases can affect all parts of the body, including the central and peripheral nervous systems, all organs and tissues, the muscles, the vasculature and the bones.

The invention relates to selected macrocyclic compounds, and their use in the treatment or prevention of diseases and disorders. In particular, though not exclusively, the invention relates to the use of selected macrocyclic compounds in the treatment or prevention of diseases that are caused by (1) cell death due to various causes and (2) inflammation. Such diseases can affect all parts of the body, including the central and peripheral nervous systems, all organs and tissues, the muscles, the vasculature and the bones.

The present invention relates to compounds of formula (I),

##STR00001## wherein R.sup.1 to R.sup.6, A.sup.1 and A.sup.2 are as described herein, and their pharmaceutically acceptable salt thereof, and compositions including the compounds and methods of using the compounds.