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.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

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.

Provided are a calcium-sensing receptor (CaSR) agonist compound and application thereof. Specifically, provided are a series of polypeptide CaSR agonist compounds and pharmaceutically acceptable salts thereof, which have agonist effects on human CaSRs to reduce plasma parathyroid hormone and serum calcium ion levels, and can be used for treatment of metabolic diseases such as primary hyperparathyroidism, secondary hyperparathyroidism, and tumor-induced hypercalcemia.

Methods, compounds, compositions and kits for the treatment and/or prevention of cancer are provided. In particular, methods for the treatment of cancer comprising the administration of a TLR2 agonist, such as a conjugate of dipalmitoyl-S-glyceryl-cysteine (Pam2Cys) and polyethylene glycol (PEG), more particularly a Pam2Cys-Ser-PEG compound, and an immunostimulant such as an anti-PD-1, anti-PDL-1, anti-PL-1, or anti-CTLA-4 immunotherapeutic, are provided.

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.

The invention provides novel compounds, compositions and formulations of liposomes, microbubbles and/or nanodroplets, and emulsions thereof, that are useful in delivery of various nucleic acids and genes (e.g., single stranded RNA, DNA, si-RNA and CRISPR constructs), as well as methods of preparation and use thereof including methods of imaging and gene delivery using ultrasound activation.

The invention relates to the method for building nanoparticle-based drug carriers and the nanoparticle based drug delivery system able to manipulate the corresponding protein corona for specific and potent drug delivery to cancer cells.