Methods and agents for modulating intracellular coenzyme A levels are described for therapeutic purposes. Increasing intracellular coenzyme A increases alternate macrophage activation resulting in suppression or resolution of an immune response for benefit in treating inflammatory diseases. Decreasing intracellular coenzyme A levels decreases alternate macrophage activation which is beneficial in treating NASH/NAFLD and various fibrotic diseases as well as reversing immune suppressing activity of tumor-associated immune cells such as macrophages for the treatment of cancer.

Solid forms of Compound I, which modulates the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compound and methods for preparing the solid forms, are described herein. The use of such solid form of Compound I and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.

A method of treatment for coronavirus disease 2019 (COVID-19) is disclosed herein. The method comprises administering a therapeutically effective dose of a combination of ribavirin and minocycline. A pharmaceutical composition comprising ribavirin and minocycline is also disclosed herein. The pharmaceutical composition may further include one or more pharmaceutical excipients.

The invention relates to a combination comprising an antineoplastic agent, e.g. an antimetabolite antineoplastic agent and a type 1 serotonin receptor (HTR1) modulator, e.g. a HTR1 antagonist. In addition the invention relates to a pharmaceutical composition comprising a combination of the invention and a pharmaceutically acceptable excipient. The invention also relates to the combination and pharmaceutical composition according to the invention for use in medicine, particularly for use in the prevention and/or treatment of a hematological malignancy.

The disclosure provides polynucleotides encoding a polypeptide including a morpholino linker. In some embodiments, the polynucleotides of the invention have increased stability compared to wild-type polynucleotides.

The compounds are nucleoside and nucleotide analogues that can be used as cardioprotective agents. The compounds include tetrahydrofuranyl or tetrahydrothienyl moieties with quaternary stereogenic all-carbon centers at the 2′ position and a phosphonate ester at C5′ position. ##STR00001##

Described herein are small molecule cap-dependent inhibitors, including the compound of the formula: ##STR00001##
which compounds that can induce the accumulation of the p53 tumor suppressor protein in cancer cells that still express wild-type p53, as well as methods of using those compounds to, among other things, treat neuroblastoma, pediatric glioblastoma multiforme or breast cancer.

Disclosed herein are oligonucleotides, such as nucleic acid inhibitor molecules, having a 4′-phosphate analog and methods of using the same, for example, to modulate the expression of a target gene in a cell. The oligonucleotide of the disclosure comprises a 5′-terminal nucleotide represented by Formula III: ##STR00001##
wherein R.sup.a, R.sup.b, B, X.sub.2 and Y are as defined in the specification. The phosphate analogs are bound to the 4′-carbon of the sugar moiety (e.g., a ribose or deoxyribose or analog thereof) of the 5′-terminal nucleotide of an oligonucleotide. Typically, the phosphate analog is an oxymethylphosphonate, where the oxygen atom of the oxymethyl group is bound to the 4′-carbon of the sugar moiety or analog thereof. An illustrative 5′-terminal nucleotide of an oligonucleotide of the disclosure may have the following chemical structure: ##STR00002##

Disclosed are co-crystal forms of N-(2-(5-(((2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetra-hydro-2H-pyran-2-yl)oxy)-3′-fluoro-[1,1′-biphenyl]-2-yl)ethyl)-acetamide and L-proline or D-proline, their pharmaceutical compositions, processes of manufacture, and methods of use for treating neurodegenerative disorders such as diabetic peripheral neuropathy.

A class of polycyclic compounds of general formula (I), of general formula (I′), or of general formula (I″), wherein Base.sup.1, Base.sup.2, Y, Y.sup.a, X.sup.a, X.sup.a1, X.sup.b, X.sup.b1, X.sup.c, X.sup.c1, X.sup.d, X.sup.d1, R.sup.1, R.sup.1a, R.sup.2, R.sup.2a, R.sup.3, R.sup.4, R.sup.4a, R.sup.5, R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8, and R.sup.8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds. ##STR00001##