A61K47/542

Short chain ceramide-based lipids and uses thereof

Provided herein, in some aspects, are delivery vehicles comprising a glycosphingolipid and an agent to be delivered attached to the glycosphingolipid. In some embodiments, the glycosphingolipid comprises an oligosaccharide and a short chain (e.g., C0-C3) ceramide. In some embodiments, the agent to be delivered is a therapeutic agent. The glycosphingolipid is able to deliver the agent to a cell or to a cellular compartment, as well as across the musical barrier. In some embodiments, agents delivered using the glycosphingolipid described herein exhibit longer half-life, compared to agents delivered alone. Methods of delivering a therapeutic agent to a subject for treating a disease using the glycosphingolipid delivery vehicle are also provided.

BIOMARKERS OF METAP2 INHIBITORS AND APPLICATIONS THEREOF
20230225996 · 2023-07-20 ·

The present disclosure relates to modified or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of, metabolic dysfunction associated with a treatment in a subject having cancer. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of, cancer comprising administering a combination of a polymer conjugated MetAP2 inhibitors and at least one second agent.

MDMA ENANTIOMERS
20230226019 · 2023-07-20 · ·

A composition for use in psychotherapeutic or medical treatment of an R(−) enantiomer of MDMA or MDA. A method of treating an individual for a medical condition (especially autism and social anxiety disorders), by administering an effective amount of a composition of an R(−) enantiomer of MDMA or MDA and treating the individual. A method of reducing neurotoxicity of MDMA and MDA, by administering an effective amount of a composition of an R(−) enantiomer of MDMA or MDA to an individual and reducing neurotoxicity of MDMA or MDA while treating the individual. A method of reducing hyperthermia of MDMA and MDA. A method of reducing physical dependence or abuse liability of MDMA and MDA.

Dosing and use of long-acting CLR/ramp agonists
11701409 · 2023-07-18 · ·

Long-acting agonistic analogs for CLR/RAMP receptors are provided that have an extended half-live in vivo. The agonists are delivered to an individual at a dose sufficient to reduce hypertension and ischemic injury, and to reduce cardiotoxicity associated with chemotherapeutic agents.

In vitro and in vivo intracellular delivery of siRNA via self-assembled nanopieces
11701379 · 2023-07-18 · ·

The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.

Diels-alder conjugation methods
11701427 · 2023-07-18 · ·

Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for producing protein-payload constructs (e.g., antibody-drug conjugates) utilizing a combination of transglutaminase and Diels-Alder techniques. Antibody-drug conjugates and compositions which comprise glutaminyl-modified antibodies, Diels-Alder adducts, and reactive payloads and are provided.

IMMODULATOR PEPTIDES COVALENTLY MODIFIED WITH SMALL MOLECULES
20230020406 · 2023-01-19 ·

This invention provides modified IGFBP-derived peptides—collectively termed “immodulator peptides”—and related compositions and methods. Chemical modifications to peptides using small molecules, and sequence extensions to immodulator core sequences exhibit new and surprising biological activities. The invention builds the combinatorial power of the immodulator peptide class further by demonstrating which core sequences bind metal or glycosaminoglycans such as heparin. The invention discloses some surprising biological properties of compositions derived from these modifications, including a host of new therapeutic and diagnostic utilities (e.g. immune modulation of TLR signaling, enhanced collagen synthesis by skin fibroblasts, and synergy with a RIG-1 agonist in killing melanoma cells). The invention also teaches methods for enhancing previously disclosed uses of immodulator peptides by showing how the modifications of the invention can boost the efficacy of immodulator peptides in a model of burn trauma.

Cytokine conjugates for the treatment of proliferative and infectious diseases

Disclosed herein are interleukin (IL) conjugates (e.g., IL-2 conjugates) and use in the treatment of one or more indications. Also described herein are pharmaceutical compositions and kits comprising one or more of the interleukin conjugates (e.g., IL-2 conjugates).

INCRETIN ANALOGUE, PREPARATION METHOD THEREFOR, AND USE THEREOF

An incretin analogue, a preparation method therefor, and the use thereof. The incretin analogue has a GLP-1R/GIPR/GCGR agonist activity, is a triple agonist, and can be used for lowering blood glucose, reducing fat and reducing weight.

BIVALENT COMPOUNDS, CONJUGATES AND USES THEREOF

There are provided bivalent compounds and conjugates thereof, the conjugates comprising a bivalent compound, a targeting moiety, and a bioactive agent, as well as pharmaceutical compositions and methods of use of the conjugate for the treatment, inhibition, or prevention of diseases and disorders which are therapeutic targets of the bioactive agent.

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