Patent classifications
A61K31/03
TUMOR SUPPRESSION BY MODULATION OF NON-CANONICAL AUTOPHAGY (LAP) IN MYELOID CELLS
Compositions and methods are provided for suppressing tumors by modulating the LAP pathway. Targeting components of the LAP pathway for specific drug design can be used as n immunotherapy strategy that modulates the tumor microenvironment. It is well established that infiltrating monocytes and macrophages play a pivotal role in shaping an immunosuppressive tumor microenvironment. By modulating LAP in the innate immune cells, the function of effector T cells can be manipulated toward an effective, cytotoxic immune response that can eliminate tumor cells. Thus, methods are provided for reducing the size or number of tumor cells and for treating cancer or other cell proliferative disorders. Further provided are methods for increasing the Th1 response or increasing IFNγ and/or TNFα expression in the tumor microenvironment by administering a LAP inhibitor.
COMPOSITIONS FOR CORONAVIRUS INFECTION TREATMENT AND/OR PREVENTION
A composition includes a compound for treating and/or preventing a coronavirus infection in a subject. The coronavirus is severe acute respiratory syndrome coronavirus (SARS-CoV)-2, SARS-CoV-1, or Middle East respiratory syndrome coronavirus (MERS-CoV). Methods include treating and/or preventing a coronavirus infection in a subject by administering the composition to the subject.
COMPOSITIONS FOR CORONAVIRUS INFECTION TREATMENT AND/OR PREVENTION
A composition includes a compound for treating and/or preventing a coronavirus infection in a subject. The coronavirus is severe acute respiratory syndrome coronavirus (SARS-CoV)-2, SARS-CoV-1, or Middle East respiratory syndrome coronavirus (MERS-CoV). Methods include treating and/or preventing a coronavirus infection in a subject by administering the composition to the subject.
IMMUNOMODULATOR COMPOUNDS
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.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.
IMMUNOMODULATOR COMPOUNDS
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.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.
Glucocorticoid receptor modulators to treat pancreatic cancer
Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The GRM may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor. The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a SGRM, such as a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.
Glucocorticoid receptor modulators to treat pancreatic cancer
Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The GRM may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor. The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a SGRM, such as a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.
N-BENZOATE GROUP SUBSTITUTED BENZOPYRROLINE-2-ONE DERIVATIVE AND USE THEREOF
Disclosed are a compound, a stereisomer and a tautomer thereof, a pharmaceutically acceptable salt thereof, and a solvate or a prodrug thereof, which can be used for preventing or treating a RORγ mediated disease. The compound has the structural formula (I).
##STR00001##
N-BENZOATE GROUP SUBSTITUTED BENZOPYRROLINE-2-ONE DERIVATIVE AND USE THEREOF
Disclosed are a compound, a stereisomer and a tautomer thereof, a pharmaceutically acceptable salt thereof, and a solvate or a prodrug thereof, which can be used for preventing or treating a RORγ mediated disease. The compound has the structural formula (I).
##STR00001##
SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF
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 propanamides, 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.