Abstract: The present invention provides, among other things, a masked cytokine comprising an attenuated interleukin 2 (IL-2) polypeptide, a VHH masking moiety, a carrier moiety and anti-PD1 targeting moiety. In some embodiments, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

Abstract: The present invention relates to an VHH masked cytokines, comprising an IL-2 polypeptide, an anti-IL-2 VHH masking moiety and a proteolytically cleavable peptide. The anti-IL-2 VHH masking moiety masks IL-2 reducing or preventing binding of the cytokine or functional fragment thereof to its cognate receptor. Upon proteolytic cleavage at a target site, the IL-2 becomes activated, which renders it capable or more capable of binding to its cognate receptor.

Abstract: The present invention relates to targeted, masked cytokines, comprising a cytokine or functional fragment thereof, a masking moiety, a targeting moiety and a proteolytically cleavable linker. The targeting moiety comprises an antigen-binding moiety that specifically binds to an antigen expressed on the surface of a target cell The masking moiety masks the cytokine or functional fragment thereof thereby reducing or preventing binding of the cytokine or functional fragment thereof to its cognate receptor, but upon proteolytic cleavage of the cleavable linker at a target site, the cytokine or functional fragment thereof becomes activated, which renders it capable or more capable of binding to its cognate receptor.

Abstract: The present invention includes methods of identifying a patient who will likely be responsive to treatment with a protein arginine N-methyltransferase 5 inhibitor, or a pharmaceutically acceptable salt thereof, and methods of treating the same.

Abstract: Disclosed are novel compounds which are useful as therapeutics, especially in anti-neoplastic therapy and in other therapeutic regimes where cysteine protease inhibition is implicated.

Abstract: Mutant enzymes and methods of use thereof are provided.

Abstract: Disclosed are novel compounds which are useful as therapeutics, especially in anti-neoplastic therapy and in other therapeutic regimes where cysteine protease inhibition is implicated.

Abstract: Methods for identifying ubiquitin ligases and ubiquitin ligase modulators are disclosed. The methods comprise combining the components of a ubiquitylation reaction and using proteins that contain motifs that recognize ubiquitylated sites in the detection of ubiquitylation.

Abstract: Compounds represented by the following structure (I) are disclosed: as are methods for making such compounds, wherein said methods comprise reacting a diacyldiketopiperazine with a first aldehyde to produce an intermediate compound; and reacting the intermediate compound with a second aldehyde to produce the class of compounds with the generic structure, where the first aldehyde and the second aldehydes are selected from the group consisting of an oxazolecarboxaldeyhyde, imidazolecarboxaldehyde, a benzaldehyde, imidazolecarboxaldehyde derivatives, and benzaldehyde derivatives, thereby forming the above compound wherein R1, R1?, R1?, R2, R3, R4, R5, and R6, X1 and X2, Y, Z, Z1, Z2, Z3, and Z4 may each be separately defined in a manner consistent with the accompanying description. Compositions and methods for treating vascular proliferation are also disclosed.

Abstract: Disclosed herein are various novel oxazolidinone, imidazolidinone, and thiazolidinone analogs and methods of treating cancer and/or microbial infection using these analogs. Particular 4-oxazolidinone compounds are shown to have anti-cancer and anti-microbial activity.

Abstract: Methods for identifying ubiquitin ligases and ubiquitin ligase modulators are disclosed. The methods comprise combining the components of a ubiquitylation reaction and using proteins that contain motifs that recognize ubiquitylated sites in the detection of ubiquitylation.

Abstract: Compounds of Formulae I-VI and derivatives thereof having anti-cancer, anti-inflammatory, and anti-microbial properties and to compositions that include one or more of compounds and their derivatives or analogs having anti-cancer, anti-inflammatory and anti-microbial properties are disclosed. Pharmaceutical compositions comprising such compounds and methods of treating cancer, inflammatory conditions, and microbial infections with the disclosed compounds or the disclosed pharmaceutical compositions are also disclosed.

Abstract: Disclosed herein are various novel oxazolidinone, imidazolidinone, and thiazolidinone analogs and methods of treating cancer and/or microbial infection using these analogs. Particular 4-oxazolidinone compounds are shown to have anti-cancer and anti-microbial activity.

Abstract: Disclosed herein are various novel oxazolidinone, imidazolidinone, and thiazolidinone analogs and methods of treating cancer and/or microbial infection using these analogs. Particular 4-oxazolidinone compounds are shown to have anti-cancer and anti-microbial activity.

Abstract: Disclosed herein are various novel oxazolidinone, imidazolidinone, and thiazolidinone analogs and methods of treating cancer and/or microbial infection using these analogs. Particular 4-oxazolidinone compounds are shown to have anti-cancer and anti-microbial activity.

Abstract: Compounds of Formulae I-VI and derivatives thereof having anti-cancer, anti-inflammatory, and anti-microbial properties and to compositions that include one or more of compounds and their derivatives or analogs having anti-cancer, anti-inflammatory and anti-microbial properties are disclosed. Pharmaceutical compositions comprising such compounds and methods of treating cancer, inflammatory conditions, and microbial infections with the disclosed compounds or the disclosed pharmaceutical compositions are also disclosed.

Abstract: Compounds of Formulae I-VI and derivatives thereof having anti-cancer, anti-inflammatory, and anti-microbial properties and to compositions that include one or more of compounds and their derivatives or analogs having anti-cancer, anti-inflammatory and anti-microbial properties are disclosed. Pharmaceutical compositions comprising such compounds and methods of treating cancer, inflammatory conditions, and microbial infections with the disclosed compounds or the disclosed pharmaceutical compositions are also disclosed.

Abstract: Compounds represented by the following structure (I), acid-addition salts and pro-drugs are disclosed: wherein the ring structure includes no substitutions, one substitution, or more than one substitution; and wherein n is equal to an integer grater than 1, preferably 2, 3, or 4; m is equal to a positive integer, preferably 1, 2 or 3, and each separate Xn and X are each separately selected from a nucleophilic residue, preferably —H, —OH, —O—CO-alkyl, —O-alkyl, —NH2, a halogen and the like; and wherein the dashed line represents a C—C bond or a C—H bond, and the dashed and solid line represents either a carbon-carbon single bond or a carbon-carbon double bond.

Abstract: Disclosed herein are various novel oxazolidinone, imidazolidinone, and thiazolidinone analogs and methods of treating cancer and/or microbial infection using these analogs. Particular 4-oxazolidinone compounds are shown to have anti-cancer and anti-microbial activity.

Abstract: Compounds of Formulae I-VI and derivatives thereof having anti-cancer, anti-inflammatory, and anti-microbial properties and to compositions that include one or more of compounds and their derivatives or analogs having anti-cancer, anti-inflammatory and anti-microbial properties are disclosed. Pharmaceutical compositions comprising such compounds and methods of treating cancer, inflammatory conditions, and microbial infections with the disclosed compounds or the disclosed pharmaceutical compositions are also disclosed.