Provided herein are compounds, compounds including traceless linkers, protein conjugates thereof, and compositions thereof. Also provided herein are methods for the treatment of diseases, disorders, and conditions, and/or the management of the symptoms thereof, associated with inflammatory diseases and autoimmune disorders further associated with the glucocorticoid receptor, glucocorticoid binding, and/or glucocorticoid receptor signalling, including administration of the compounds or payloads via traceless linker-payloads, and protein conjugates thereof.

An antibody-drug conjugate (ADC) has a structure represented by Formula (I): a pharmaceutically acceptable salt thereof wherein Ab is an antibody without glycans (i.e., the protein portion an antibody); G.sub.1 and G.sub.2 are glycan moieties, which may be the same or different; C.sub.n1 and C.sub.n2 are conjugation moieties, which may be the same or different; L.sub.1 and L.sub.2 are linker moieties, which may be the same or different; D.sub.1 and D.sub.2; are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y≠0.

Synthesizing a docetaxel-aconitic anhydride conjugate using docetaxel, including: mixing aconitic anhydride with a chlorinating reagent to produce a first mixture; dissolving the first mixture in an organic solvent to produce a dissolved mixture; stirring the dissolved mixture; evaporating the organic solvent from the dissolved mixture to produce a second mixture; washing the second mixture with an impurity remover to remove impurities and to produce an aconitic anhydride chloride solution; and mixing the docetaxel with the produced aconitic anhydride chloride solution to produce the docetaxel-aconitic anhydride conjugate.

Synthesizing a docetaxel-aconitic anhydride conjugate using docetaxel, including: mixing aconitic anhydride with a chlorinating reagent to produce a first mixture; dissolving the first mixture in an organic solvent to produce a dissolved mixture; stirring the dissolved mixture; evaporating the organic solvent from the dissolved mixture to produce a second mixture; washing the second mixture with an impurity remover to remove impurities and to produce an aconitic anhydride chloride solution; and mixing the docetaxel with the produced aconitic anhydride chloride solution to produce the docetaxel-aconitic anhydride conjugate.

In one embodiment, the invention provides a chimeric antigen receptor (CAR) T cell which is conjugated to a bi-functional molecule which is specific for both an extracellular binding domain of the chimeric antigen receptor (CAR) T cell and prostate-specific membrane antigen (PSMA). The chimeric antigen receptor (CAR) T cell contains a T cell signaling domain and the extracellular binding domain of the chimeric antigen receptor (CAR) T cell is not specific for prostate-specific membrane antigen (PSMA). Compositions and methods of treatment using these CAR T cells are also disclosed.

The present application relates to cyclosporine analogues and their use in medical applications, including as antiviral compounds and in gene therapy.

Provided herein are bifunctional compounds that bind cyclin-dependent kinase 9 (CDK9) and/or promote targeted ubiquitination for the degradation of CDK9. In particular, provided are compounds that can bind CDK9, a protein whose dysregulation is implicated in a variety of cancers, and can promote CDK9′s degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon, VHL). The E3 ubiquitin ligase can ubiquitinate CDK9, marking it for proteasomal degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds. Also provided are methods of treating cancer, and methods of promoting the degradation of CDK9 protein by E3 ubiquitin ligase activity in a subject or biological sample by administering a compound or composition described herein.

The present invention provides a compound or a pharmaceutically acceptable salt thereof containing a modified oligonucleotide with a length of 8 to 80 consecutive nucleosides, in which the modified oligonucleotide has a nucleobase sequence containing at least 8 consecutive nucleobases contained in a nucleobase sequence of any one of SEQ ID NOs: 3 to 73. With the compound or a pharmaceutically acceptable salt thereof, it is possible to treat a disease or a condition against which inhibition of CALM2 gene expression by controlling of the CALM2 gene expression is effective (particularly, congenital long QT syndrome).

A proteolysis targeting chimera (PROTAC), and an application thereof in preparation of a drug for treating a related disease. Specifically disclosed are a compound as represented by formula (I) and a pharmaceutically acceptable salt thereof.

The present disclosure generally relates to novel Tregitope-blood component conjugates and modified polypeptides comprising Tregitopes, with said modified peptides being capable of reacting with blood components to form such Tregitope-blood component conjugates. In aspects, the Tregitope-blood component conjugates include a blood component which acts as a carrier protein (e.g., albumin), and further include a modified polypeptide comprising one or more regulatory T cell epitopes (termed “Tregitopes”), the polypeptide having been modified by attaching a reactive moiety to the polypeptide that is capable of forming a bond (e.g., a covalent linkage) with a reactive functionality on the blood component. The present disclosure also relates to methods of using said Tregitope-blood component conjugates and modified polypeptides comprising Tregitopes in the treatment and prevent of autoimmune disorders, such as type 1 diabetes.