The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders and activators of CD137. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by CD137.

Compositions of dendrimers conjugated with one or more therapeutic agents that decrease exosome secretion and methods of use thereof for treating, alleviating, and/or preventing one or more symptoms associated with one or more neurological disease or disorders, cancer, inflammatory diseases, bacterial and viral infections, and other disorders have been developed. Preferably, the therapeutic agents are one or more agents that inhibit or reduce activity and/or quantity of neutral sphingomyelinase 2 (nSMase2) such as small molecule inhibitors of nSMase2. Compositions are particularly suited for reducing Aβ plaque formation, reducing tau propagation, improving cognition, or combinations thereof in a subject with psychiatric and neurological disorders. Compositions are also suited for treating, alleviating, and/or preventing one or more symptoms associated with cancer, bacterial and viral infections, and inflammatory diseases. Methods of treating a human subject having one or more of the diseases and disorders are provided.

Compositions of dendrimers conjugated with one or more therapeutic agents that decrease exosome secretion and methods of use thereof for treating, alleviating, and/or preventing one or more symptoms associated with one or more neurological disease or disorders, cancer, inflammatory diseases, bacterial and viral infections, and other disorders have been developed. Preferably, the therapeutic agents are one or more agents that inhibit or reduce activity and/or quantity of neutral sphingomyelinase 2 (nSMase2) such as small molecule inhibitors of nSMase2. Compositions are particularly suited for reducing Aβ plaque formation, reducing tau propagation, improving cognition, or combinations thereof in a subject with psychiatric and neurological disorders. Compositions are also suited for treating, alleviating, and/or preventing one or more symptoms associated with cancer, bacterial and viral infections, and inflammatory diseases. Methods of treating a human subject having one or more of the diseases and disorders are provided.

A polymer-prostaglandin conjugate comprising: a polymer backbone comprising a plurality of moieties of formula (I): where: T represents a triazole moiety; Q is independently selected at each occurrence and may be present or absent and when present represents a linking group; R is selected from the group consisting of linear or branched hydrocarbon; D is selected from prostaglandins; and L is a group of formula (II) wherein R.sup.5 is selected from hydrogen and C.sub.1 to C.sub.6 alkyl; (R) indicates the end of the group bonded to the R group; and (D) indicates the end of the group attached to the group D. ##STR00001##

A polymer-prostaglandin conjugate comprising: a polymer backbone comprising a plurality of moieties of formula (I): where: T represents a triazole moiety; Q is independently selected at each occurrence and may be present or absent and when present represents a linking group; R is selected from the group consisting of linear or branched hydrocarbon; D is selected from prostaglandins; and L is a group of formula (II) wherein R.sup.5 is selected from hydrogen and C.sub.1 to C.sub.6 alkyl; (R) indicates the end of the group bonded to the R group; and (D) indicates the end of the group attached to the group D. ##STR00001##

The present invention relates to a targeted protease degradation (TED) platform, and specifically to a conjugate of target molecule-linker-E3 ligase ligand as shown in formula I, R.sub.T-L1-R.sub.E3 (formula I), wherein R.sub.T is a monovalent group of the target molecule, R.sub.E3 is a monovalent group of the E3 ligase ligand, L1 is the linker linking A and B, and L1 is as shown in formula II below: —W-L2-W.sup.2— (II).

The presently disclosed subject matter relates to nitric oxide-releasing particles for delivering nitric oxide, and their use in biomedical and pharmaceutical applications.

The presently disclosed subject matter relates to nitric oxide-releasing particles for delivering nitric oxide, and their use in biomedical and pharmaceutical applications.

Non-crushable pill formulations and methods of using the formulations are disclosed. A non-crushable pill formulation for preventing unintended use of a drug, comprising a polymer, the polymer forming a polymer backbone of the complex; cross-linkers, the cross-linkers connecting the polymer backbone through covalently bonding to form at least one inner cavity within the complex; and the drug, the drug being trapped either covalently or non-covalently in the at least one inner cavity within the complex, wherein the drug is protected from releasing outside of the complex.

Non-crushable pill formulations and methods of using the formulations are disclosed. A non-crushable pill formulation for preventing unintended use of a drug, comprising a polymer, the polymer forming a polymer backbone of the complex; cross-linkers, the cross-linkers connecting the polymer backbone through covalently bonding to form at least one inner cavity within the complex; and the drug, the drug being trapped either covalently or non-covalently in the at least one inner cavity within the complex, wherein the drug is protected from releasing outside of the complex.