The present invention is directed to elucidating the mechanism of formation of autophagosomal membranes that emerge via convergence of secretory and endosomal pathways and providing therapeutic approaches to the treatment of several acute respiratory syndrome coronavirus 1 (SARS) and 2 SARS-CoV-2), MERS-CoV and numerous other autophagy-mediated diseases based upon this mechanism. This process is targeted by microbial factors such as coronaviral membrane modulating proteins and represents a potential target for agents which may be used in the treatment of SARS, COVID and MERS. The present invention is also directed to compositions and methods for the treatment of SARS, COVID and/or MERS and other autophagy-mediated disease states.

The present invention features compositions and methods for treating proliferative diseases such as cancer (e.g., sarcoma, pancreas, prostate, head and neck, liver, and breast cancer) that inhibit the growth of NF-κB and/or Hippo associated neoplasias.

This invention relates to deuterated analogs of etifoxine of Formula 1, solvates, prodrugs, and pharmaceutically acceptable salts thereof, as well as to methods for their preparation and use, and to pharmaceutical compositions. Briefly, this invention is generally directed to deuterated analogs of etifoxine as well as to methods for their preparation and use, and to pharmaceutical compositions containing the same.

This invention relates to deuterated analogs of etifoxine of Formula 1, solvates, prodrugs, and pharmaceutically acceptable salts thereof, as well as to methods for their preparation and use, and to pharmaceutical compositions. Briefly, this invention is generally directed to deuterated analogs of etifoxine as well as to methods for their preparation and use, and to pharmaceutical compositions containing the same.

Methods and compounds are disclosed for wound healing by modulating autophagy. A formulation for modulating autophagy comprises a first modulating compound (FAM) selected from compounds having the general structure (I): ##STR00001## wherein: L represents a linker selected from —C≡C—, (a tolan), —CH═CH— (a stilbene, preferably trans); or —CR.sub.a═CR.sub.b— a stilbene derivative; where R.sub.a and R.sub.b are independently H or phenyl optionally substituted with —(R.sup.3).sub.p or —(R.sup.4).sub.q; R.sup.1 to R.sup.4 are independent substituents at any available position of the phenyl rings, preferably at 3, 3′, 4, 4′, and/or 5, 5′; and m, n, p, and q are independently 0, 1, 2, or 3 representing the number of substituents of the rings, respectively, but at least one of m or n must be ≥1. Each R.sup.1 to R.sup.2 is independently selected from substituents described herein, including but not limited to hydroxyl, alkoxy, halo, halomethyl and glycosides. The formulation may also include an auxiliary autophagy modulating compound (AAM) as described herein. The formulation may include a hydrogel formed by the compounds themselves or otherwise and may include salts and/or complexes.

Methods and compounds are disclosed for wound healing by modulating autophagy. A formulation for modulating autophagy comprises a first modulating compound (FAM) selected from compounds having the general structure (I): ##STR00001## wherein: L represents a linker selected from —C≡C—, (a tolan), —CH═CH— (a stilbene, preferably trans); or —CR.sub.a═CR.sub.b— a stilbene derivative; where R.sub.a and R.sub.b are independently H or phenyl optionally substituted with —(R.sup.3).sub.p or —(R.sup.4).sub.q; R.sup.1 to R.sup.4 are independent substituents at any available position of the phenyl rings, preferably at 3, 3′, 4, 4′, and/or 5, 5′; and m, n, p, and q are independently 0, 1, 2, or 3 representing the number of substituents of the rings, respectively, but at least one of m or n must be ≥1. Each R.sup.1 to R.sup.2 is independently selected from substituents described herein, including but not limited to hydroxyl, alkoxy, halo, halomethyl and glycosides. The formulation may also include an auxiliary autophagy modulating compound (AAM) as described herein. The formulation may include a hydrogel formed by the compounds themselves or otherwise and may include salts and/or complexes.

Methods and compounds are disclosed for wound healing by modulating autophagy. A formulation for modulating autophagy comprises a first modulating compound (FAM) selected from compounds having the general structure (I): ##STR00001## wherein: L represents a linker selected from —C≡C—, (a tolan), —CH═CH— (a stilbene, preferably trans); or —CR.sub.a═CR.sub.b— a stilbene derivative; where R.sub.a and R.sub.b are independently H or phenyl optionally substituted with —(R.sup.3).sub.p or —(R.sup.4).sub.q; R.sup.1 to R.sup.4 are independent substituents at any available position of the phenyl rings, preferably at 3, 3′, 4, 4′, and/or 5, 5′; and m, n, p, and q are independently 0, 1, 2, or 3 representing the number of substituents of the rings, respectively, but at least one of m or n must be ≥1. Each R.sup.1 to R.sup.2 is independently selected from substituents described herein, including but not limited to hydroxyl, alkoxy, halo, halomethyl and glycosides. The formulation may also include an auxiliary autophagy modulating compound (AAM) as described herein. The formulation may include a hydrogel formed by the compounds themselves or otherwise and may include salts and/or complexes.

Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The GRM may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor.

The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a SGRM, such as a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The GRM may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor.

The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a SGRM, such as a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

Provided herein are compounds, compositions, and methods useful for the treatment of breast cancer, particularly triple negative breast cancers. In certain aspects, provided herein are compounds of formula (I): ##STR00001##
or a pharmaceutically acceptable salt or solvate thereof. In certain aspects, provided herein are compositions comprising any of the compounds provided herein. In certain aspects, provided herein are methods for the treatment of cancer in a subject in need thereof comprising administering to the subject an effective amount of any of the compounds or compositions provided herein.