The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

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 present disclosure provides bioorthogonal compositions for delivering agents in a subject. The disclosure also provides methods of producing the compositions, as well as methods of using the same.

The present invention relates to methods and compositions for the treatment of BAF-related disorders such as cancers and viral infections.

Disclosed is the use of the reactive components of the inverse electron-demand Diels Alder reaction for chemical masking and unmasking in vitro. This can be applied in complex chemical reactions and, particularly in the synthesis of biomolecules, e.g. on solid supports. The reactice components are a dienophile, particularly a trans-cyclooctene, and a diene, particularly a tetrazine.

Among other things, the present disclosure provides compounds comprising universal antibody binding moieties and targeting moieties. In some embodiments, provided compounds recruit various types of antibodies to diseased cells such as cancer cells, and induce immune activities to kill such cells. Provided technologies are useful for treating various diseases including cancer.

The present disclosure relates to a method for labeling a radioisotope includes providing a cyclooctyne compound represented by the following formula (I), and to which a biomolecule, a fluorescent dye, or a nanoparticle compound is bound, and reacting the cyclooctyne compound with a quinone compound represented by the following formula (II) and labeled with the radioisotope in room temperature; a radiolabeling compound represented by the following formula (II), for labeling a molecule having a cyclooctyne moiety; and a composition for medical diagnosis or for treating cancer comprising a quinone compound represented by the following formula (II) and labeled with the radioisotope:

##STR00001##

in formula (I), Z is the biomolecule, the fluorescent dye, or the nanoparticle compound,

##STR00002##

in formula (II), b is 0 or an integer from 1 to 10; L is CH.sub.2, COO, or CONH; M is the radioisotope.

Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of c-MYC protein. The disclosed PROTACs typically include a first targeting moiety that binds to c-MYC (M.sub.c-MYC) which may be derived from a substituted heterocycle that binds to c-MYC such as a substituted pyrazole. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (M.sub.E3). As such, the disclosed PROTACS may be described as having a formula M.sub.c-MYC-L-M.sub.E3 or M.sub.E3-L-M.sub.c-MYC.

The present disclosure provides bioorthogonal compositions for delivering agents in a subject. The disclosure also provides methods of producing the compositions, as well as methods of using the same.