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

Described are compounds for targeting proteases, e.g. serine proteases and their use in the diagnostic methods and methods for treatment of respiratory diseases such as cystic fibrosis. The compounds have the structure [H][B]-[A]; wherein [H] is a hydrophilic group, [B] is a subsite recognition group and [A] is a binding group; wherein A has the formula: C(0)CH.sub.2NR.sup.1COOR.sup.2 and wherein [B] has the structure: (i) [COCH.sub.2NR.sup.3]m-, or (ii) -[AA1-AA2]- or (iii) -(AA1-C0-CH.sub.2NR.sup.3) or (iv) (COCH.sub.2NR.sup.3-AA1)- or (v) (C0CH.sub.2NR.sup.4-AA1-AA3)-.

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.

In antibody-drug conjugates having tubulysin analog as the warhead, according to formula (III)

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the acetate group in the Tuv subunit (dotted box) demonstrates improved stability against hydrolytic cleavage.

Provided herein are bispecific antigen-binding molecules that bind HER2 and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human HER2. The bispecific antigen-binding molecules cluster on the surface of HER2 IHC2+ and IHC3+ cells, and are internalized into the cellular lysosomes. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.

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.

Compounds and compositions are disclosed in which a quaternized drug unit is linked to a targeting ligand unit from which a tertiary amine-containing drug is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease using the compounds and compositions of the invention are also disclosed.

The present invention provides one or more compounds of formula (I) for conjugation to small molecules, polymers, peptides, proteins, antibodies, antibody fragments etc.

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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. ##STR00001##

Provided herein are bispecific antigen-binding molecules that bind HER2 and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably nonoverlapping) epitopes of the extracellular domain of human HER2. The bispecific antigen-binding molecules cluster on the surface of HER2 IHC2+ and IHC3+ cells, and are internalized into the cellular lysosomes. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.