Tetrahydrocannabinol derivatives and medical use thereof, in particular to the compounds represented by general formula (I), or stereoisomers, solvates, metabolites, pharmaceutically acceptable salts or cocrystals thereof, wherein the definitions of substituents in general formula (I) are the same as those in the description

##STR00001##

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.

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.

Disclosed are chemical entities which are compounds of formula (I):

##STR00001##

or pharmaceutically acceptable salts thereof; wherein Y, R.sup.a, R.sup.a′, R.sup.b, R.sup.c, X.sub.1, X.sub.2, X.sub.3, R.sup.d, Z.sub.1, and Z.sub.2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.

Na/K-ATPase ligands are provided that comprise a compound of formula (I) and are capable of binding to the α1 Na/K-ATPase and decreasing the endocytosis of α1 Na/K-ATPase, such that expression of the α1 Na/K-ATPase is restored in the plasma membrane of cells and tumor growth and invasion is reduced. Pharmaceutical compositions are further provided that include a compound of formula (I) and a pharmaceutically-acceptable vehicle, carrier, or excipient. Methods of treating a cancer are further included and comprise administering to a subject an effective amount of a Na/K-ATPase ligand.

The invention relates to cleavable chemistry in general, and in particular, to tunable fluorescence using cleavable linkers present in fluorochrome-quencher conjugates.

Disclosed herein are detectable moieties and detectable conjugates comprising one or more detectable moieties. In some embodiments, the disclosed detectable moieties have a narrow wavelength and are suitable for multiplexing. Also disclosed are methods of labeling one or more targets within a biological specimen using any of the detectable conjugates and/or detectable moieties described herein.

The present disclosure relates to carbon monoxide releasing molecules (“CORMs”), and methods of synthesizing and applying the molecules. More specifically, this disclosure relates to structurally tunable CORMS, compounds containing CORMS (and salts thereof). An exemplary compound includes: ##STR00001##

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I):

##STR00001##

including stereoisomers, salts and tautomers thereof, wherein R.sup.1, R.sup.2, R.sup.3, L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5, L.sup.6, M.sup.1, M.sup.2, A, q, w and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

Provided herein are polynucleotides and CRISPR effector proteins configured to be covalently bound together in a CRISPR complex. The polynucleotides can be further modified to modulate the activity of the CRISPR complex. Modification of the polynucleotide and CRISPR effector protein can be used to improve the efficacy of target binding and/or cleavage.