Provided herein are new crystalline form(s) of succinate salt(s) of 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (also known as ribociclib), pharmaceutical compositions comprising the same, methods of treatment using the same and methods of making the same.

The invention concerns KDM5A inhibitors for use in prevention or treatment of idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, necrotizing autoimmune myopathy, and in particular sporadic inclusion body myositis, and diagnosis of these diseases based on KDM5A expression levels in muscle tissue. The invention further concerns pharmaceutical compositions comprising KDM5A inhibitors for use in prevention or treatment of idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, necrotizing autoimmune myopathy, and in particular sporadic inclusion body myositis.

The invention concerns KDM5A inhibitors for use in prevention or treatment of idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, necrotizing autoimmune myopathy, and in particular sporadic inclusion body myositis, and diagnosis of these diseases based on KDM5A expression levels in muscle tissue. The invention further concerns pharmaceutical compositions comprising KDM5A inhibitors for use in prevention or treatment of idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, necrotizing autoimmune myopathy, and in particular sporadic inclusion body myositis.

The invention herein discloses a pharmaceutical combination for use in the treatment of cancer comprising a DNA ligase IV inhibitor and a PARP inhibitor in synergistically effective amounts for simultaneous, separate or sequential administration to a subject in need thereof.

The invention herein discloses a pharmaceutical combination for use in the treatment of cancer comprising a DNA ligase IV inhibitor and a PARP inhibitor in synergistically effective amounts for simultaneous, separate or sequential administration to a subject in need thereof.

The invention herein discloses a pharmaceutical combination for use in the treatment of cancer comprising a DNA ligase IV inhibitor and a PARP inhibitor in synergistically effective amounts for simultaneous, separate or sequential administration to a subject in need thereof.

Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors described herein.

Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors described herein.

Compounds described herein may be used for the treatment of neurodegenerative diseases linked to protein misfolding, including prion diseases, Alzheimer's disease, Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and also other neurodegenerative, degenerative, metabolic and ischemic conditions. Indeed, NAD metabolism impairment is also a critical feature in brain ischemia/reperfusion injury, Wallerian degeneration, kidney failure, multiple sclerosis, aging, and metabolic disorders such as diabetes mellitus. Therapies that elevate or stabilize NAD levels may thus have broad potential for treating many severely debilitating neurological and metabolic conditions. Evidence is provided herein with compounds from 8 lead series for NAD restoring properties and for therapeutic efficacy in cellular and/or animal models of prion disease, PD and ALS.

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.