Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with cancer, including tubulysins and protein (e.g., antibody) drug conjugates thereof.

A mitochondrial-targeted PARP inhibitor is provided herein, as well as methods of making and using the mitochondrial-targeted PARP inhibitor.

The invention described herein pertains to the diagnosis, imaging, and/or treatment of pathogenic cell populations. In particular, the invention described herein pertains to the diagnosis, imaging, and/or treatment of diseases caused by PSMA expressing cells, such as prostate cancer cells, using compounds capable of targeting PSMA expressing cells.

The invention described herein pertains to the diagnosis, imaging, and/or treatment of pathogenic cell populations. In particular, the invention described herein pertains to the diagnosis, imaging, and/or treatment of diseases caused by PSMA expressing cells, such as prostate cancer cells, using compounds capable of targeting PSMA expressing cells.

The present technology relates to compounds, kits, compositions, and methods useful for the treatment of numerous pathologies including dementia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases, spinal cord injury, traumatic brain injury, diabetes and metabolic syndrome, defective wound healing, and/or sensorineural hearing and vision loss.

This application relates to compounds of Formula (I-a) or Formula (I-b), or is salts or solvates thereof. R.sup.1 is (CH.sub.2).sub.5CH.sub.3 or comprises 2-4 fused benzene rings. R.sup.2 is I, Br, F, Cl, H, OH, OCH.sub.3, NH.sub.2, NO.sub.2 or CH.sub.3. R.sup.3 is a peptide-bonded glycine, aspartate or glutamate or is glutamate peptide bonded through C.sub.delta. L is CH.sub.2NH, (CH.sub.2).sub.2NH, (CH.sub.2).sub.3NH, or (CH.sub.2).sub.4NH. R.sup.4 is a radiometal chelator optionally bound by a radiometal. Variable n is 1-3. The compounds may be useful for imaging prostate specific membrane antigen (PSMA)-expressing tissues or for treating PSMA-expressing diseases (e.g. cancer).

In one aspect, the present disclosure provides tubulysin analogs of the formula (I) wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X.sub.1, X.sub.2, X.sub.3, and A.sub.1 are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. ##STR00001##

Improved processes for the preparation of tubulysin compounds, tubulysin drug linker compounds, and their intermediates are disclosed.

Compounds that affect quorum sensing (QS) in Staphylococcus aureus and related Staphylococcus species (e.g., S. epidermidis). Compounds which modulate one or more of the four AgrC receptors of Staphylococcus species, particularly of Staphylococcus aureus. Modulation includes inhibition or activation of one or more of these four AgrC receptors. These compounds are useful for bacterial interference and are useful for treating bacterial infections, particularly staphylococcal infection. Treatment can include combination of one or more of the compounds of the invention in combination with one or more antibiotics.

Compounds of formula (I) as inhibitors of DCN1 and compositions containing the same are disclosed. Methods of using the DCN1 inhibitors in the treatment of diseases and conditions wherein inhibition of DCN1 provides a benefit, like oxidative stress-related diseases and conditions, neurodegenerative diseases and conditions, metabolic disorders, and muscular nerve degeneration, also are disclosed.

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