This invention provides compounds that have spirocyclic E3 Ubiquitin Ligase targeting moieties (Degrons), which can be used as is or linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

The invention relates to benzodiazepine derivatives with antiproliferative activity and more specifically to benzodiazepine compounds of formulae (I), (II), (TI) and (T2). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

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The present invention relates to a tyrosine kinase inhibitor (“TKI”) conjugate or a pharmaceutically acceptable salt thereof, wherein said conjugate comprises a plurality of TKI moieties -D covalently conjugated via at least one moiety -L.sup.1-L.sup.2- to a polymeric moiety Z, wherein -L.sup.1- is covalently and reversibly conjugated to -D and -L.sup.2- is covalently conjugated to Z and wherein -L.sup.1- is a linker moiety and -L.sup.2- is a chemical bond or a spacer moiety; and to related aspects.

A conjugate comprising the following topoisomerase inhibitor derivative (A*): where Y is H or F, with a single overall linker moiety connecting two topoisomerase inhibitor derivatives to a Ligand Unit, wherein the topoisomerase inhibitor derivatives are cleavable from the Ligand Unit. Also provided is A* with the linking unit attached, and intermediates for their synthesis.

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This disclosure generally relates to therapeutic conjugates that covalently bind to a biological target. Methods of administering the compositions to a subject in need thereof are also provided herein.

The disclosure relates to new compounds, including bifunctional compounds, to be used as modulators of ubiquitination for targeted protein degradation.

Reagents and methods to cloak and uncloak RNA polymers and applications thereof are provided. Photocloaking molecules are used to label RNA polymers. Radiant energy is used to remove photoreleaseable protecting adducts and revert a RNA polymer to its native form.

The present disclosure includes the use of a miRNA inhibitor for treating a tauopathy associated with a decreased level of SIRT1 protein or SIRT1 gene expression, PGC-1α protein and/or PGC-α gene expression, and/or CD36 and/or CD36 gene expression.

Disclosed herein are compounds that target SMARCA2, SMARCA4 or BRM, causing their degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

The present invention provides compounds, compositions thereof, and methods of using the same.