The invention provides bridged diindole compounds, related pharmaceutical compositions and methods of use thereof, for the prevention, palliation and/or treatment of nervous system disorders.

The present disclosure describes a method to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds of the invention can decrease the rate of proliferation of drug-resistant cancer cells, such as glioma, lung cancer, and uterine sarcoma.

The present disclosure describes a method to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds of the invention can decrease the rate of proliferation of drug-resistant cancer cells, such as glioma, lung cancer, and uterine sarcoma.

Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

The present disclosure provides for compounds of formula (I)

##STR00001##

wherein A.sup.2, A.sup.3, A.sup.4, A.sup.6, A.sup.7, A.sup.8, R.sup.15, R.sup.A, R.sup.5, R.sup.9, R.sup.10A, R.sup.10B, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of formula (I).

The present disclosure provides for compounds of Formula (I)

##STR00001##

wherein A.sup.2, A.sup.3, A.sup.4, A.sup.6, A.sup.7, A.sup.8, A.sup.15, R.sup.A, R.sup.5, R.sup.9, R.sup.10A, R.sup.10B, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

The present disclosure provides for compounds of Formula (I)

##STR00001##

wherein A.sup.2, A.sup.3, A.sup.4, A.sup.6, A.sup.7, A.sup.8, A.sup.15, R.sup.A, R.sup.5, R.sup.9, R.sup.10A, R.sup.10B, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

The invention provides a compound according to formula (I) or a tautomer thereof, wherein R.sup.1, R.sup.2, R.sup.3, W.sub.1, W.sub.2, W.sub.3, A, X and Y are as defined in the specification. The compounds are potent inhibitors of the serine/threonine kinase, TAK1. The present invention further provides: a pharmaceutical composition comprising a compound of formula (I) and at least one pharmaceutically acceptable excipient; a compound of formula (I) for use as a medicament (for example for the treatment or prophylaxis of a condition selected from cancer, inflammatory diseases, autoinflammatory diseases and autoimmune diseases); and a method of treating or preventing a disease or disorder comprising administering a pharmaceutically effective amount of a compound of formula (I) to a subject in need thereof.

##STR00001##

The invention provides a compound according to formula (I) or a tautomer thereof, wherein R.sup.1, R.sup.2, R.sup.3, W.sub.1, W.sub.2, W.sub.3, A, X and Y are as defined in the specification. The compounds are potent inhibitors of the serine/threonine kinase, TAK1. The present invention further provides: a pharmaceutical composition comprising a compound of formula (I) and at least one pharmaceutically acceptable excipient; a compound of formula (I) for use as a medicament (for example for the treatment or prophylaxis of a condition selected from cancer, inflammatory diseases, autoinflammatory diseases and autoimmune diseases); and a method of treating or preventing a disease or disorder comprising administering a pharmaceutically effective amount of a compound of formula (I) to a subject in need thereof.

##STR00001##