This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

The present invention relates to methods of treating HBV, COVID-19 or SARS-CoV-2 infection in a human patient, wherein the methods comprise administration of a therapeutically effective amount of a TLR7 agonist, or a pharmaceutically acceptable salt thereof.

The present invention relates to methods of treating HBV, COVID-19 or SARS-CoV-2 infection in a human patient, wherein the methods comprise administration of a therapeutically effective amount of a TLR7 agonist, or a pharmaceutically acceptable salt thereof.

The present invention relates to a composition for prevention or treatment of bronchial asthma comprising a PKR inhibitor as an active ingredient. The PKR inhibitor and derivatives thereof according to the present invention can be used as a pharmaceutical for prevention, amelioration or treatment of bronchial asthma and as a supplementary health food because the PKR inhibitor and derivatives thereof reduce the total counts of inflammatory cells, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid of neutrophilic severe asthma-induced mice, reduce airway inflammation and airway hyper-responsiveness, and reduce inflammatory mediators.

The present invention relates to a composition for prevention or treatment of bronchial asthma comprising a PKR inhibitor as an active ingredient. The PKR inhibitor and derivatives thereof according to the present invention can be used as a pharmaceutical for prevention, amelioration or treatment of bronchial asthma and as a supplementary health food because the PKR inhibitor and derivatives thereof reduce the total counts of inflammatory cells, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid of neutrophilic severe asthma-induced mice, reduce airway inflammation and airway hyper-responsiveness, and reduce inflammatory mediators.

Disclosed herein are methods for determining whether a PAR4 inhibitor should be administered to a human subject, the methods comprising administering a PAR4 inhibitor to a subject determined to have a “G” allele for a single-nucleotide polymorphism (SNP) at rs773902, and not administering a PAR4 inhibitor to a subject determined to have an “A” allele for the SNP at rs773902. A genotyping assay can be used to determine the SNP.

Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds inhibit PD-1/PD-L1 interaction and are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

##STR00001##

Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds inhibit PD-1/PD-L1 interaction and are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

##STR00001##

A compound of general formula (1) ##STR00001## [wherein: R.sub.1 and R.sub.2, which are the same or different, each represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower cycloalkyl group, a lower alkanoyl group, a halogen substituted lower alkyl group, a lower alkoxy group, a halogen substituted lower alkoxy group, a cyano group, a cross-linked methylenedioxy group, an ethylenedioxy group, a propylenedioxy group, a lower alkylthio group, a lower alkylsulfonyl group, a carboxyl group, a lower alkoxycarbonyl group, a lower alkylamide group, a lower alkylamino alkylene amide group, an amino group, an alkylamino group, a hydroxy group, a functional group represented by general formula (2), or a functional group represented by general formula (3)
—CONH(CH.sub.2).sub.p—R.sub.3  (2) [wherein R.sub.3 represents a di-lower alkylamino group, a morpholino group, a piperidino group, a 2-methyl-piperidino group, or a 2-oxo-pyrrolidinyl group; p represents an integer from 2 to 6]; ##STR00002## [wherein, R.sub.4 represents a lower alkyl group]; m and n each represent an integer from 0 to 3; the term lower represents a carbon number of 1 to 6; and the halogen atom represents a fluorine, chlorine or bromine atom] can inhibit endoplasmic reticulum stress to a greater extent as compared to known chemical chaperones. The compound thus can be used suitably as an agent for preventing, ameliorating or treating various diseases that are caused by endoplasmic reticulum stress.