The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

Provided are methods of selecting a patient with cancer and/or treating a patient with cancer that comprises a deleterious alteration in FBXW7 and/or an amplification of CCNL1 for CDK11 inhibitor and/or ATR inhibitor treatment. For example, the method of selecting a patient afflicted with a cancer likely to benefit from a CDK11 inhibitor and/or ATR inhibitor treatment, the method comprising: obtaining a biological sample; testing the sample for i) loss of function FBXW7, optionally for a deleterious mutation in F box WD-repeat containing protein (FBXW7) substrate binding domain and/or ii) upregulated CCNL1, optionally a gain or amplification of CCNL1; and selecting the patient having i) loss of function FBXW7, optionally a deleterious mutation in the FBWX7 substrate-binding domain or ii) upregulated CCNL1, optionally a gain or amplification of CCNL1, as likely to benefit and/or for treatment with the CDK11 inhibitor and/or ATR inhibitor.

Provided are methods of selecting a patient with cancer and/or treating a patient with cancer that comprises a deleterious alteration in FBXW7 and/or an amplification of CCNL1 for CDK11 inhibitor and/or ATR inhibitor treatment. For example, the method of selecting a patient afflicted with a cancer likely to benefit from a CDK11 inhibitor and/or ATR inhibitor treatment, the method comprising: obtaining a biological sample; testing the sample for i) loss of function FBXW7, optionally for a deleterious mutation in F box WD-repeat containing protein (FBXW7) substrate binding domain and/or ii) upregulated CCNL1, optionally a gain or amplification of CCNL1; and selecting the patient having i) loss of function FBXW7, optionally a deleterious mutation in the FBWX7 substrate-binding domain or ii) upregulated CCNL1, optionally a gain or amplification of CCNL1, as likely to benefit and/or for treatment with the CDK11 inhibitor and/or ATR inhibitor.

The present disclosure provides, among other things, improved compositions and methods for treating muscular dystrophy. For example, the disclosure provides methods for treating Duchenne muscular dystrophy patients having a mutation in the DMD gene that is amenable to exon 53 skipping by administering an effective amount of golodirsen.

Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors described herein.

Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors described herein.

This invention is in the field of medicinal chemistry. In particular, the invention relates to anew class of small-molecules having a tetrahydroindazole structure which function as modulators (e.g., activators or inhibitors) of sigma-1 and/or sigma-2 receptors, and their use as therapeutics for the treatment of cancer and other diseases (e.g., neurological conditions) characterized with sigma-1 and/or sigma-2 receptor activity.

This invention is in the field of medicinal chemistry. In particular, the invention relates to anew class of small-molecules having a tetrahydroindazole structure which function as modulators (e.g., activators or inhibitors) of sigma-1 and/or sigma-2 receptors, and their use as therapeutics for the treatment of cancer and other diseases (e.g., neurological conditions) characterized with sigma-1 and/or sigma-2 receptor activity.