A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

The present invention relates to a benzamide compound and a preparation method, use and pharmaceutical composition thereof. The benzamide compound represented by formula (I) is a STAT3 inhibitor, and can be used to prevent and/or treat a disease related to STAT3 activity, such as a tumor, autoimmune disease, renal disease, cardiovascular disease, inflammation, metabolic/endocrine dysfunction, and neurological disease.

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This disclosure provides a method for inhibiting, delaying, or reducing malignant cell growth in a subject with cancer, comprising administering to the subject a combination therapy comprising an effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds to semaphorin-4D (SEMA4D) and an effective amount of an epigenetic modulating agent, e.g., a histone deacetylase (HDAC) inhibitor (HDACi) a DNA methyltransferase (DNMT) inhibitor (DNMTi), or any combination thereof. The disclosure further provides a pharmaceutical composition comprising the combination therapy.

This disclosure provides a method for inhibiting, delaying, or reducing malignant cell growth in a subject with cancer, comprising administering to the subject a combination therapy comprising an effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds to semaphorin-4D (SEMA4D) and an effective amount of an epigenetic modulating agent, e.g., a histone deacetylase (HDAC) inhibitor (HDACi) a DNA methyltransferase (DNMT) inhibitor (DNMTi), or any combination thereof. The disclosure further provides a pharmaceutical composition comprising the combination therapy.

This disclosure provides a method for inhibiting, delaying, or reducing malignant cell growth in a subject with cancer, comprising administering to the subject a combination therapy comprising an effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds to semaphorin-4D (SEMA4D) and an effective amount of an epigenetic modulating agent, e.g., a histone deacetylase (HDAC) inhibitor (HDACi) a DNA methyltransferase (DNMT) inhibitor (DNMTi), or any combination thereof. The disclosure further provides a pharmaceutical composition comprising the combination therapy.

The present invention relates to combinations for use and methods of treating cancers that express prostate specific membrane antigen (PSMA). In particular, the invention provides novel therapies based on the combination of a PSMA therapeutic agent, such as radiolabeled Compound I, and immuno-oncology (I-O) therapeutic agents, wherein said I-O therapeutic agents are selected from the group consisting of LAG-3 inhibitors, TIM-3 inhibitors, GITR agonists, TGF-β inhibitors, IL15/IL-15RA complex, PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors.

The present invention relates to combinations for use and methods of treating cancers that express prostate specific membrane antigen (PSMA). In particular, the invention provides novel therapies based on the combination of a PSMA therapeutic agent, such as radiolabeled Compound I, and immuno-oncology (I-O) therapeutic agents, wherein said I-O therapeutic agents are selected from the group consisting of LAG-3 inhibitors, TIM-3 inhibitors, GITR agonists, TGF-β inhibitors, IL15/IL-15RA complex, PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors.

Disclosed herein are Ral-antagonist compounds that covalently bind to binding sites in RalA, and efficaciously inhibit Ral activity. The compounds include aryl sulfonyl fluoride compounds of the general structure of wherein X and Y are independently C or N, and R.sub.4 is C.sub.1-C.sub.4 alkyl, —OCH.sub.3, —OCH.sub.2CH.sub.3, —OCH(CH.sub.3).sub.2, —(SO.sub.2)CH.sub.3, —OH, or halo. These compounds expand Ral-inhibiting therapeutic options for treating Ral-driven cancers and one embodiment of the present disclosure is directed to the use of such compounds to treat cancer.

The present invention relates to the preventive and therapeutic uses of acid sphingomyelinase inhibitors (FIASMAs) such as psychotropic medications and non-psychotropic compounds having FIASMA activity, for lowering the risk of death and/or intubation in patient suffering from a viral infection caused by at least one betacoronavirus, in particular by the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) through reduced cell and blood concentration of ceramides.