The present disclosure relates to compounds and methods which may be useful for modulating the expression of a target gene comprising a CGG trinucleotide repeat sequence and treating diseases and conditions in which the target gene plays an active role. The present disclosure provides compounds and methods for modulating the expression of fmr1 and fmr2, and provides compounds and methods for treating fragile X syndrome and fragile XE syndrome.

The present application provides bifunctional compounds of Formula (X): ##STR00001##
or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for protein kinases. The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases.

The invention provides compositions, kits and methods to treat a hyperproliferative disorder with an agent that increases expression of MCR1 and an MCR1 ligand. The invention also provides a method of treating drug-resistant melanoma, comprising administering an MCR1 ligand to a patient in need thereof. The present invention also provides in certain embodiments a melanoma-targeting conjugate comprising Formula I:
T-L-X
wherein T is a MCR1 ligand, L is a linker, and X an anti-cancer composition, for the therapeutic treatment of a hyperproliferative disorder. The present invention also provides methods, kits and uses of the conjugate of Formula I.

The present disclosure relates to benzoselenophene-based compounds, method of preparing the benzoselenophene-based compounds, pharmaceutical compositions and antibody-drug conjugates including the benzoselenophene-based compounds.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of IL-17. 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 IL-17.

Described herein are compounds of Formula (I), polymers and implantable elements comprising compounds of Formula (II), and compositions and methods of use thereof. In particular, the compounds, modified polymers, implantable elements and related compositions may be used in methods for the prevention and treatment of a disease, disorder or condition in a subject.

The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.

Disclosed are a type of mitochondria-targeted polypeptides, the preparation method and the uses thereof. The polypeptide is abbreviated as MTP. The synthesis method of the present disclosure is simple, and the mitochondria-targeted polypeptide prepared by the method can specifically target the mitochondria of cells and are basically non-toxic to cells. In addition, these synthesized polypeptides demonstrate good cell-membrane-penetrating properties, and can conveniently undergo further multi-functional derivation and modification, thereby providing a potential delivery tool for the preparation of a mitochondria-targeted medicament.

The present invention relates to a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (a dual-linker) containing a 2,3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.

The present invention relates to a compound comprising an EZH2 inhibitor and an E3 ligase binder, and a pharmaceutical composition for preventing or treating EZH2-associated disease and a pharmaceutical composition for selective protein degradation containing the same as an active ingredient. Since the compound of the present invention can selectively degrade EZH2, it can be effectively used for the treatment of EZH2-related diseases and cancers, particularly, cancers in which EZH2 is overexpressed, and can be usefully used for the selective degradation of EZH2.