The present invention relates to bi-functional compounds which function to recruit endogenous proteins to an E3 ubiquitin ligase for degradation, and methods for using same. More specifically, the present disclosure provides specific proteolysis targeting chimera (PROTAC) molecules which find utility as modulators of targeted ubiquitination of a variety of polypeptides and other proteins, in particular the androgen receptor of a slice variant of AR which lacks the LBD, labelled as AR-V7, which are then degraded and/or otherwise inhibited by the compounds as described herein.

Provided herein are compounds and pharmaceutical compositions useful in modulating kinase activity, and related diseases. Also provided herein are methods of treating an eye disease or disorder in a subject. Also provided herein are methods of reducing intraocular pressure in a subject. Also provided herein are methods of modulating kinase activity in a cell. Also provided herein are methods of making the compounds provided herein, and compounds useful for the preparation of the compounds provided herein.

Disclosed herein are methods and compounds for inducing DDB1- and CUL4-associated factor 16 (DCAF16)-mediated protein degradation in mammalian cells. In some embodiments, also disclosed herein are methods of modulating the substrate selectivity of a DCAF16-CUL4-RBX1-DDB1 complex (CRL4) for modulating protein degradation.

The invention relates to compounds that inhibit DUBs, particularly USP9X. The invention also includes methods of inhibiting DUBs, including USP9X, and methods of treating cancers.

The invention relates to compounds that inhibit DUBs, particularly USP9X. The invention also includes methods of inhibiting DUBs, including USP9X, and methods of treating cancers.

The invention provides a long-acting parathyroid hormone peptide (PTH) that is retained in a subject's blood serum for periods of time that greatly exceed the natural hormone. The long-acting PTH is conjugated to at the carbon 3 position of a non-hormonal vitamin D via a scaffold of discreet length that facilitates its purification, detection, solubility, and efficacy at the PTH receptor (PTHR). The PTH may be conjugated to the non-hormonal vitamin D via a 36 mer poly(ethylene glycol) moiety (PTH-PEG36-VitD). The invention also provides optimized manufacturing methods and formulations. The PTH-PEG36-VitD has a vastly-improved serum half-life and bioavailability when compared to a non-conjugated PTH peptide. PTH-PEG36-VitD also significantly increases serum calcium, reduces urinary calcium, and reduces serum phosphate.

Disclosed are bispecific compounds (degraders) that target ALK for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat diseases and disorders characterized or mediated by aberrant ALK activity

Disclosed are bispecific compounds (degraders) that target ALK for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat diseases and disorders characterized or mediated by aberrant ALK activity

The invention provides non-hormonal Vitamin D conjugated to G-CSF or compounds with G-CSF activity or GM-CSF or compounds having GM-CSF activity singly or in combination that result in increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms.

Fibroblast activation protein (FAP)-targeting compounds (e.g., conjugates); a method for imaging cancer or fibrosis; and methods for treating an inflammatory disease/disorder and cancer.