In alternative embodiments, provided are uncharged bis-oxime antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). In alternative embodiments, provided are pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound as provided herein.

In alternative embodiments, provided are uncharged bis-oxime antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). In alternative embodiments, provided are pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound as provided herein.

Disclosed are compounds, for example, compounds of formula I,

##STR00001##

wherein R, R.sub.0, R.sub.1-R.sub.8, n, X, Y, Y′, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition, for example, cancer.

Disclosed are compounds, for example, compounds of formula I,

##STR00001##

wherein R, R.sub.0, R.sub.1-R.sub.8, n, X, Y, Y′, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition, for example, cancer.

This invention provides Degronimers that have E3 Ubiquitin Ligase targeting moieties (Degrons) that can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation. The invention also provides Degrons that can be used to treat disorders mediated by cereblon or an Ikaros family protein, and methods of use and compositions thereof as well as methods for their preparation.

The present invention provides a heterocyclic compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I): ##STR00001## wherein each symbol is as described in the specification, or a salt thereof, is useful as an agent for the prophylaxis or treatment of narcolepsy.

The present invention provides a heterocyclic compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I): ##STR00001## wherein each symbol is as described in the specification, or a salt thereof, is useful as an agent for the prophylaxis or treatment of narcolepsy.

Disclosed are methods of treating a non-infectious ocular immunoinflammatory disorder in a subject. Methods of reducing a symptom, e.g., ocular redness, of a non-infectious ocular immunoinflammatory disorder in a subject, and pharmaceutical composition containing an SP blocker, an SP antagonist, an SP receptor blocker or an SP receptor antagonist as an active component and a pharmaceutically acceptable carrier or excipient are also described.

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (II) or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, R.sup.9, R.sup.10, R.sup.12, Z, Y and m are as defined herein.

##STR00001##

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (II) or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, R.sup.9, R.sup.10, R.sup.12, Z, Y and m are as defined herein.

##STR00001##