Compositions and methods for characterizing cancer cells by determining a marker of PGK1 activity. For example, methods are provided for predicting a patient response to a PGK1 inhibitor, a MEK/ERK inhibitor, an EGFR inhibitor, or a PIN1 inhibitor therapy. Methods for treating patients with such therapies are likewise provided.

Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II):

##STR00001##

including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3, R.sup.4, R.sup.5, R.sup.6a, R.sup.6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II):

##STR00001##

including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3, R.sup.4, R.sup.5, R.sup.6a, R.sup.6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

In the broadest aspect, the invention provides a composition for and a method of prophylactic and/or therapeatic treatment of a animal/mammal for any viral disease, mixed bacterial and viral infections, bacterial infections, bacterial endotoxins, bacterial exotoxins, autoimmune diseases, and cellular or humoral mediated allergic conditions that is caused by any virus that relies on the maintenance of specific calcium ion concentrations for the post ribosomal RNA synthesis processing of vital protein transistion, transportation and processing of viral structural components by utilizing a therapeutic amount of a blocker selected from the group consisting of a calcium channel blocker, a metabolic thereof, a calmodulin blocker and a metabolite thereof, and a plumaceutical acceptable diluent or carrier: and/or is caused by damage to the animal/mammal by a pathological immune response to antigens.

In the broadest aspect, the invention provides a composition for and a method of prophylactic and/or therapeatic treatment of a animal/mammal for any viral disease, mixed bacterial and viral infections, bacterial infections, bacterial endotoxins, bacterial exotoxins, autoimmune diseases, and cellular or humoral mediated allergic conditions that is caused by any virus that relies on the maintenance of specific calcium ion concentrations for the post ribosomal RNA synthesis processing of vital protein transistion, transportation and processing of viral structural components by utilizing a therapeutic amount of a blocker selected from the group consisting of a calcium channel blocker, a metabolic thereof, a calmodulin blocker and a metabolite thereof, and a plumaceutical acceptable diluent or carrier: and/or is caused by damage to the animal/mammal by a pathological immune response to antigens.

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors. R-isomers, and non-hydroxylated and/or non-chiral propenamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors. R-isomers, and non-hydroxylated and/or non-chiral propenamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: Z is a group of formula: (II) wherein P and Q are each independently CR.sub.12R.sub.13; or one of P and Q is NR.sub.14 and the other is CR.sub.12R.sub.13; the group X—Y is —NHSO.sub.2— or —SO2NH—; R.sub.1 is H, CN or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, heteroaryl, SO.sub.2NR.sub.16R.sub.17, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H or halo; and R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.16 and R.sub.17 are each independently H or alkyl; R.sub.15 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m and n are each independently 0, 1, 2 or 3. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: Z is a group of formula: (II) wherein P and Q are each independently CR.sub.12R.sub.13; or one of P and Q is NR.sub.14 and the other is CR.sub.12R.sub.13; the group X—Y is —NHSO.sub.2— or —SO2NH—; R.sub.1 is H, CN or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, heteroaryl, SO.sub.2NR.sub.16R.sub.17, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H or halo; and R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.16 and R.sub.17 are each independently H or alkyl; R.sub.15 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m and n are each independently 0, 1, 2 or 3. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

Provided herein are dry powder formulations comprising epinephrine alone or in combination with at least one enabling agent suitable for nasal application. Also provided are unit dose forms and devices comprising such formulations and methods of using such formulations for the treatment of various conditions including anaphylaxis, anaphylactoid reaction, respiratory conditions, hemodynamic collapse, and for administration during cardiopulmonary arrest and other life-threatening conditions.