Provided are methods of selecting a patient with cancer and/or treating a patient with cancer that comprises a deleterious alteration in FBXW7 and/or an amplification of CCNL1 for CDK11 inhibitor and/or ATR inhibitor treatment. For example, the method of selecting a patient afflicted with a cancer likely to benefit from a CDK11 inhibitor and/or ATR inhibitor treatment, the method comprising: obtaining a biological sample; testing the sample for i) loss of function FBXW7, optionally for a deleterious mutation in F box WD-repeat containing protein (FBXW7) substrate binding domain and/or ii) upregulated CCNL1, optionally a gain or amplification of CCNL1; and selecting the patient having i) loss of function FBXW7, optionally a deleterious mutation in the FBWX7 substrate-binding domain or ii) upregulated CCNL1, optionally a gain or amplification of CCNL1, as likely to benefit and/or for treatment with the CDK11 inhibitor and/or ATR inhibitor.

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.

Stable pharmaceutical compositions comprising a compound of Formula (I) or a stereoisomer or a pharmaceutically acceptable derivative thereof are disclosed. Formula (I)

##STR00001##

Stable pharmaceutical compositions comprising a compound of Formula (I) or a stereoisomer or a pharmaceutically acceptable derivative thereof are disclosed. Formula (I)

##STR00001##

The present invention is based on the identification of a cohort of polyurethane block copolymers that are particularly suited for use in pharmaceutical polymeric drug-device units and which offer improved control of drug release. In particular, there is provided a polymeric drug-device unit comprising a polyurethane block copolymer obtainable by reacting together a poly(alkylene oxide); a difunctional compound; a difunctional isocyanate; and optionally a block copolymer comprising poly(alkylene oxide) blocks; and quinagolide as a pharmaceutically active agent. The drug-device units may find application in the treatment and/or prevention of endometriosis.

The present invention is based on the identification of a cohort of polyurethane block copolymers that are particularly suited for use in pharmaceutical polymeric drug-device units and which offer improved control of drug release. In particular, there is provided a polymeric drug-device unit comprising a polyurethane block copolymer obtainable by reacting together a poly(alkylene oxide); a difunctional compound; a difunctional isocyanate; and optionally a block copolymer comprising poly(alkylene oxide) blocks; and quinagolide as a pharmaceutically active agent. The drug-device units may find application in the treatment and/or prevention of endometriosis.

Compounds of Formula I and the pharmaceutically acceptable salts thereof are disclosed Formula I. The variables X.sup.1, X.sup.2, and R.sup.1-4 are disclosed herein. The compounds are useful for treating cancer and related proliferative diseases. Pharmaceutical compositions containing compounds of Formula I and methods of treatment comprising administering compounds of Formula I are also disclosed.

##STR00001##

Compounds of Formula I and the pharmaceutically acceptable salts thereof are disclosed Formula I. The variables X.sup.1, X.sup.2, and R.sup.1-4 are disclosed herein. The compounds are useful for treating cancer and related proliferative diseases. Pharmaceutical compositions containing compounds of Formula I and methods of treatment comprising administering compounds of Formula I are also disclosed.

##STR00001##

Compounds of Formula I and the pharmaceutically acceptable salts thereof are disclosed Formula I. The variables X.sup.1, X.sup.2, and R.sup.1-4 are disclosed herein. The compounds are useful for treating cancer and related proliferative diseases. Pharmaceutical compositions containing compounds of Formula I and methods of treatment comprising administering compounds of Formula I are also disclosed.

##STR00001##

The present invention provides compounds of formula (Id) that are prodrugs of catecholamine for use in treatment of neurodegenerative diseases and disorders. The present invention also provides pharmaceutical compositions comprising compounds of the invention and methods of treating neurodegenerative or neuropsychiatric diseases and disorders using the compounds of the invention, in particular Parkinson's disease.