Abstract: Disclosed are substituted pyrrolo[2,3-d]pyrimidine compounds. The disclosed compounds are shown to be useful in inhibiting the growth of cancer cell lines and treating cancer and cell proliferative disorders.

Abstract: Disclosed are substituted pyrrolidones and piperidones which may be utilized as EZH2 targeting agents. The substituted pyrrolidones and piperidones may include substituted 2-pyrrolidones and 2-piperidones. The disclosed pyrrolidones and piperidones may be used in pharmaceutical compositions and methods for treating cell proliferative disorders such as cancer.

Abstract: Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of c-MYC protein. The disclosed PROTACs typically include a first targeting moiety that binds to c-MYC (Mc-MYC) which may be derived from a substituted heterocycle that binds to c-MYC such as a substituted pyrazole. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). As such, the disclosed PROTACS may be described as having a formula Mc-MYC-L-ME3 or ME3-L-Mc-MYC.

Abstract: Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of IDO protein. The disclosed PROTACs typically include a first targeting moiety that binds to IDO (MIDO). The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). As such, the disclosed PROTACS may be described as having a formula MIDO-L-ME3 or ME3-L-MIDO.

Abstract: Disclosed herein are substituted phenyl compounds of formula I as defined herein that may be utilized as inhibitors of the interaction between the subunits of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels, such as HCN1, and an auxiliary subunit of HCN channels which is the tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b). The disclosed compounds may be used in pharmaceutical compositions and methods for treating neurological diseases and disorders such as depression, and in particular Major Depressive Disorder (MDD).

Abstract: Disclosed are covalent inhibitors of enhancer zeste homolog 2 (EZH2) which may be utilized as EZH2 targeting agents. The disclosed compounds may be characterized as substituted 3-amino-5-phenylbenzamide compounds. The disclosed compounds may be utilized as covalent inhibitors of EZH2 and further may be derivatized to form proteolysis-targeting chimeric molecules (PROTACs) that target EZH2 for degradation. The disclosed compounds and PROTACs may be used in pharmaceutical compositions and methods for treating cell proliferative disorders associated with EZH2 activity, such as cancer.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to anew class of small-molecules having a tetrahydroindazole structure which function as modulators (e.g., activators or inhibitors) of sigma-1 and/or sigma-2 receptors, and their use as therapeutics for the treatment of cancer and other diseases (e.g., neurological conditions) characterized with sigma-1 and/or sigma-2 receptor activity.

Abstract: Disclosed are compounds that bind to embryonic ectoderm development (EED) protein and proteolysis-targeting chimeric (PROTAC) derivatives thereof that induce degradation of EED. The disclosed compounds may be characterized as substituted [1,2,4]triazolo[4,3-c]pyrimidin-5-amine compounds. The disclosed PROTAC derivatives thereof typically include a first targeting moiety that binds to EED (MEED) which may be derived from the disclosed [1,2,4]triazolo [4,3-c]pyrimidin-5-amine compounds that bind to EED. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). As such, the disclosed PROTACS may be described as having a formula MEED-L-ME3 or ME3-L-MEED.

Abstract: Disclosed are substituted pyrrolidones and piperidones which may be utilized as EZH2 targeting agents. The substituted pyrrolidones and piperidones may include substituted 2-pyrrolidones and 2-piperidones. The disclosed pyrrolidones and piperidones may be used in pharmaceutical compositions and methods for treating cell proliferative disorders such as cancer.

Abstract: Disclosed are compounds which may be utilized to inhibit transcription by RNA Polymerase II (Pol II), and in particular to disrupt the Super Elongation Complex (SEC). The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with the biological activity of SEC, and in particular, diseases and disorders that are associated with high levels of expression of genes whose expression is SEC-dependent and that promote, support, or otherwise are required for the disease or disorder such as cancers.

Abstract: Disclosed are substituted heterocycle compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.

Abstract: Disclosed are indazole compounds and derivatives thereof for use as modulators of the activity of mitogen-activated protein kinase 4 (MEK4). The disclosed compounds include 3-Arylindazoles which may be formulated in pharmaceutical composition for treating cell proliferative diseases and disorders associated with MEK4 activity, including cancer.

Abstract: Disclosed are compounds, pharmaceutical compositions, and methods of treatment. The disclosed compounds are based on fused 1,4-diazepine and pyrrolidinedione scaffolds.

Abstract: Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of IDO protein. The disclosed PROTACs typically include a first targeting moiety that binds to IDO (MIDO). The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). As such, the disclosed PROTACS may be described as having a formula MIDO-L-ME3 or ME3-L-MIDO.

Abstract: Disclosed are compounds, pharmaceutical compositions, and methods of treatment. The disclosed compounds are based on fused 1,4-diazepine and pyrrolidinedione scaffolds.

Abstract: Disclosed are substituted heterocycle compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.

Abstract: Disclosed are substituted heterocycle compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.

Abstract: Disclosed are compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds and pharmaceutical compositions for treating a subject in need thereof. The disclosed compounds inhibit the activity of tissue transglutaminase 2 (TG2). As such, the disclosed compounds and pharmaceutical compositions may be utilized in methods for treating a subject having or at risk for developing a disease or disorder that is associated with TG2 activity which may be cell proliferative diseases and disorders such as cancer.

Abstract: Disclosed are indazole compounds and derivatives thereof for use as modulators of the activity of mitogen-activated protein kinase 4 (MEK4). The disclosed compounds include 3-Arylindazoles which may be formulated in pharmaceutical composition for treating cell proliferative diseases and disorders associated with MEK4 activity, including cancer.

Abstract: Disclosed are substituted heterocycle compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.