The present disclosure provides compounds and methods useful for inhibiting SARM1 and/or treating and/or preventing axonal degeneration.

The present invention discloses a number of polycyclic amines that are useful as opioid receptor modulators. The compounds of the invention are useful in both therapeutic and diagnostic methods, including for treating pain, neurological disorders, cardiac disorders, bowel disorders, drug and alcohol addiction, drug overdose, urinary disorders, respiratory disorders, sexual dysfunction, psoriasis, graft rejection or cancer.

The present invention discloses a number of polycyclic amines that are useful as opioid receptor modulators. The compounds of the invention are useful in both therapeutic and diagnostic methods, including for treating pain, neurological disorders, cardiac disorders, bowel disorders, drug and alcohol addiction, drug overdose, urinary disorders, respiratory disorders, sexual dysfunction, psoriasis, graft rejection or cancer.

Compounds used as labels with properties comparable to known fluorescent compounds. The compounds are conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

Compounds used as labels with properties comparable to known fluorescent compounds. The compounds are conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

There are described RORγ modulators of the formula (I),

##STR00001##

and formula (II)

##STR00002##

or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

There are described RORγ modulators of the formula (I),

##STR00001##

and formula (II)

##STR00002##

or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

Novel selective estrogen receptor degraders (SERDs) according to the formula:

##STR00001##

pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein either R.sup.1 or R.sup.2 is independently selected from Cl, F, —CF.sub.3, or —CH.sub.3, and the other is hydrogen, and methods for their use are provided.

Novel selective estrogen receptor degraders (SERDs) according to the formula:

##STR00001##

pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein either R.sup.1 or R.sup.2 is independently selected from Cl, F, —CF.sub.3, or —CH.sub.3, and the other is hydrogen, and methods for their use are provided.

Described herein are compositions and methods for modifying eukaryotic cells, for example, to express a transgene of interest and/or to produce an expanded population of cells ex vivo. Using the compositions and methods of the disclosure, a population of eukaryotic cells, such as a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) may be transduced to express a gene of interest by contacting the cells with a viral vector, such as a lentiviral vector, and a poloxamer. Additionally, the compositions and methods described herein can be used to promote the proliferation or survival of a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) ex vivo, for example, by contacting the cells with a poloxamer. Examples of poloxamers that may be used in conjunction with the compositions and methods of the disclosure are those having a molar mass in excess of 10,000 g/mol, as well as those having a molar mass of polyoxypropylene subunits greater than 2,000 g/mol and/or an ethylene oxide content of greater than 40% by mass.