The disclosure relates to compositions comprising PU.1 inhibitors as well as methods of making and using the same. In some embodiments, methods of screening compounds for PU.1 inhibition are disclosed. In some embodiments, methods of screening a plurality of compounds for PU.1 inhibition are disclosed. In some embodiments, lambda-beta binding (LBB) motifs are used to screen compounds for PU.1 inhibition. In some embodiments, methods of treating neurodegenerative disorders are disclosed. In some embodiments pharmaceutical compounds are provided. In some embodiments, methods of treating Alzheimer's disease, inflammation, or excessive myelin uptake with PU.1 inhibitors are disclosed.

The present invention provides a novel use of a compound having a plasminogen activator inhibitor-1 (PAI-1) inhibitory effect. Specifically, a compound having a PAI-1 inhibitory effect is used as an intranostimulator, an immune checkpoint inhibitor, an inhibitor for exacerbation of tumor cells caused by PD-L1, or an enhancer of immunotherapy for tumors, based on the inhibitory effect of the compound on expression induction of immune checkpoint molecules.

The present invention provides a novel use of a compound having a plasminogen activator inhibitor-1 (PAI-1) inhibitory effect. Specifically, a compound having a PAI-1 inhibitory effect is used as an intranostimulator, an immune checkpoint inhibitor, an inhibitor for exacerbation of tumor cells caused by PD-L1, or an enhancer of immunotherapy for tumors, based on the inhibitory effect of the compound on expression induction of immune checkpoint molecules.

Provided are formulations and methods for treating one or more genitourinary conditions. The formulations may include a therapeutic agent that includes a calcium channel blocker, a rho kinase inhibitor, or a combination thereof. The methods may include locally administering a therapeutic agent into a ureter. Systems for delivering a therapeutic agent also are provided.

Provided are formulations and methods for treating one or more genitourinary conditions. The formulations may include a therapeutic agent that includes a calcium channel blocker, a rho kinase inhibitor, or a combination thereof. The methods may include locally administering a therapeutic agent into a ureter. Systems for delivering a therapeutic agent also are provided.

Provided are formulations and methods for treating one or more genitourinary conditions. The formulations may include a therapeutic agent that includes a calcium channel blocker, a rho kinase inhibitor, or a combination thereof. The methods may include locally administering a therapeutic agent into a ureter. Systems for delivering a therapeutic agent also are provided.

In alternative embodiments, provided are pharmaceutical compositions comprising combinations of drugs, including products of manufacture and kits, and methods for using them, for treating, preventing, ameliorating, slowing the progress of, decreasing the severity of or preventing a coronavirus infection, or a COVID-19 or a 2019-nCoV (or so-called Wuhan coronavirus) infection, or an infection caused by a virus in the subfamily Orthocoronavirinae, or a virus in the family Coronaviridae, or a virus in the order Nidovirales. In alternative embodiments, combinations, or cocktails, of a drug or drugs as provided herein are administered either enterally, parenterally and/or by inhalation. In alternative embodiments, combinations, or cocktails, of drugs as provided herein are used to block intracellular metabolic pathways and prevent progression of the infection to clinical illness and death. In alternative embodiments, novel aerosol, spray or mist or powder formulations for inhalation are provided. In alternative embodiments, provided are therapeutic combinations of drugs or a drug, a pharmaceutical dosage form, a drug delivery device, or a product of manufacture, comprising: opaganib or YELIVA™, or opaganib or YELIVA™ and oral and/or inhaled chloroquine (or ARALEN™) chloroquine phosphate, chloroquine diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™), with or without azithromycin, wherein optionally each or all of the opaganib, the chloroquine (or ARALEN™), chloroquine phosphate, chloroquine diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™), and/or azithromycin, and others, are in or formulated as a formulation for inhalation, for example, formulated as an aerosol, spray, mist, liquid or powder.

In alternative embodiments, provided are pharmaceutical compositions comprising combinations of drugs, including products of manufacture and kits, and methods for using them, for treating, preventing, ameliorating, slowing the progress of, decreasing the severity of or preventing a coronavirus infection, or a COVID-19 or a 2019-nCoV (or so-called Wuhan coronavirus) infection, or an infection caused by a virus in the subfamily Orthocoronavirinae, or a virus in the family Coronaviridae, or a virus in the order Nidovirales. In alternative embodiments, combinations, or cocktails, of a drug or drugs as provided herein are administered either enterally, parenterally and/or by inhalation. In alternative embodiments, combinations, or cocktails, of drugs as provided herein are used to block intracellular metabolic pathways and prevent progression of the infection to clinical illness and death. In alternative embodiments, novel aerosol, spray or mist or powder formulations for inhalation are provided. In alternative embodiments, provided are therapeutic combinations of drugs or a drug, a pharmaceutical dosage form, a drug delivery device, or a product of manufacture, comprising: opaganib or YELIVA™, or opaganib or YELIVA™ and oral and/or inhaled chloroquine (or ARALEN™) chloroquine phosphate, chloroquine diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™), with or without azithromycin, wherein optionally each or all of the opaganib, the chloroquine (or ARALEN™), chloroquine phosphate, chloroquine diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™), and/or azithromycin, and others, are in or formulated as a formulation for inhalation, for example, formulated as an aerosol, spray, mist, liquid or powder.

In alternative embodiments, provided are pharmaceutical compositions comprising combinations of drugs, including products of manufacture and kits, and methods for using them, for treating, preventing, ameliorating, slowing the progress of, decreasing the severity of or preventing a coronavirus infection, or a COVID-19 or a 2019-nCoV (or so-called Wuhan coronavirus) infection, or an infection caused by a virus in the subfamily Orthocoronavirinae, or a virus in the family Coronaviridae, or a virus in the order Nidovirales. In alternative embodiments, combinations, or cocktails, of a drug or drugs as provided herein are administered either enterally, parenterally and/or by inhalation. In alternative embodiments, combinations, or cocktails, of drugs as provided herein are used to block intracellular metabolic pathways and prevent progression of the infection to clinical illness and death. In alternative embodiments, novel aerosol, spray or mist or powder formulations for inhalation are provided. In alternative embodiments, provided are therapeutic combinations of drugs or a drug, a pharmaceutical dosage form, a drug delivery device, or a product of manufacture, comprising: opaganib or YELIVA™, or opaganib or YELIVA™ and oral and/or inhaled chloroquine (or ARALEN™) chloroquine phosphate, chloroquine diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™), with or without azithromycin, wherein optionally each or all of the opaganib, the chloroquine (or ARALEN™), chloroquine phosphate, chloroquine diphosphate and/or hydroxychloroquine (optionally, PLAQUENIL™), and/or azithromycin, and others, are in or formulated as a formulation for inhalation, for example, formulated as an aerosol, spray, mist, liquid or powder.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):

##STR00001##

and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.