The present invention relates to compounds which inhibit histone deacetylase activity and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing these compounds. The present invention also relates to methods of treating and preventing hematological cell proliferative disorders, such as multiple myeloma, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Compositions and methods for treating and preventing respiratory symptoms related to viral and bacterial infections are described. The composition includes water, ionic minerals, trace minerals, a niacin-related compound, and an optional ingredient. The optional ingredient is mastic gum, a prebiotic, or both. The niacin-related compound is methyl nicotinate, nicotinic acid, nicotinamide, niacin, or a combination of two or more of the foregoing. The method involves nasal, auricular, or oral administration or a combination of two or more of the foregoing routes of administration to a human or other mammal.

Compositions and methods for treating and preventing respiratory symptoms related to viral and bacterial infections are described. The composition includes water, ionic minerals, trace minerals, a niacin-related compound, and an optional ingredient. The optional ingredient is mastic gum, a prebiotic, or both. The niacin-related compound is methyl nicotinate, nicotinic acid, nicotinamide, niacin, or a combination of two or more of the foregoing. The method involves nasal, auricular, or oral administration or a combination of two or more of the foregoing routes of administration to a human or other mammal.

Provided herein are methods for treating a cancer in a subject having a tumor with interstitial fluid pressure (IFP) of at least 10 mmHg, comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or prodrug thereof, which is an inhibitor of the interaction between the PD-1 receptor and its ligand PD-L1 and which is not a protein, alone, or in combination with other agents, e.g., in combination with the use of anti-PD-1/PD-L1 antibodies, in combination with an inhibitor of the CTLA-4/B7 interaction, or in combination with an inhibitor binding to VEFG.

The present invention provides an anti-inflammatory type immune-enhancing agent that simultaneously induces an anti-inflammatory action and an immune-enhancing action. An anti-inflammatory type immune-enhancing agent containing at least one kind selected from a heterocyclic compound represented by the formula (I)

##STR00001##

wherein each symbol is as described in the DESCRIPTION, or a salt thereof, and an isothiocyanate compound represented by the formula S═C═N—R.sup.5 (II) wherein the symbol is as described in the DESCRIPTION, as an active ingredient.

The present invention provides an anti-inflammatory type immune-enhancing agent that simultaneously induces an anti-inflammatory action and an immune-enhancing action. An anti-inflammatory type immune-enhancing agent containing at least one kind selected from a heterocyclic compound represented by the formula (I)

##STR00001##

wherein each symbol is as described in the DESCRIPTION, or a salt thereof, and an isothiocyanate compound represented by the formula S═C═N—R.sup.5 (II) wherein the symbol is as described in the DESCRIPTION, as an active ingredient.

The object of the present invention is to provide a mitochondrial dysfunction improving agent comprising a vitamin K derivative having a high deliverability to mitochondria.

A mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising at least one of a carboxylic acid ester of an active vitamin K represented by a general formula (1) or a salt thereof, and

##STR00001##

(wherein, R.sub.1 and R.sub.2 are a hydrogen atom, respectively, or a substituent selected from glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof; and at least either of R.sub.1 and R.sub.2 is glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof. R.sub.3 is a group represented by a general formula (2), or a general formula (3). n is an integer of 1 to 7)

##STR00002##

a mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising a carboxylic acid ester of an active vitamin K or a salt thereof (in the general formula (1), R.sub.1 and R.sub.2 is a carboxylic acid residue selected from a group consisting of R.sub.4OOCCH.sub.2CH.sub.2CO— and R.sub.4OOCCH.sub.2CH.sub.2CH.sub.2CO—. R.sub.3 represents the above general formula (2) or (3). R.sub.4 is a C1-C3 alkyl group.).

The object of the present invention is to provide a mitochondrial dysfunction improving agent comprising a vitamin K derivative having a high deliverability to mitochondria.

A mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising at least one of a carboxylic acid ester of an active vitamin K represented by a general formula (1) or a salt thereof, and

##STR00001##

(wherein, R.sub.1 and R.sub.2 are a hydrogen atom, respectively, or a substituent selected from glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof; and at least either of R.sub.1 and R.sub.2 is glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof. R.sub.3 is a group represented by a general formula (2), or a general formula (3). n is an integer of 1 to 7)

##STR00002##

a mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising a carboxylic acid ester of an active vitamin K or a salt thereof (in the general formula (1), R.sub.1 and R.sub.2 is a carboxylic acid residue selected from a group consisting of R.sub.4OOCCH.sub.2CH.sub.2CO— and R.sub.4OOCCH.sub.2CH.sub.2CH.sub.2CO—. R.sub.3 represents the above general formula (2) or (3). R.sub.4 is a C1-C3 alkyl group.).

The present disclosure relates to methods of a malignant rhabdoid tumor (MRT), a rhabdoid tumor of the kidney (RTK), an atypical teratoid/rhabdoid tumor (AT/RT), an epithelioid malignant peripheral nerve sheath tumor, a myoepithelial carcinoma, and/or a renal medullary carcinoma by using an EZH2 inhibitor in combination with one or more additional treatment modalities.

The present disclosure relates to methods of a malignant rhabdoid tumor (MRT), a rhabdoid tumor of the kidney (RTK), an atypical teratoid/rhabdoid tumor (AT/RT), an epithelioid malignant peripheral nerve sheath tumor, a myoepithelial carcinoma, and/or a renal medullary carcinoma by using an EZH2 inhibitor in combination with one or more additional treatment modalities.