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

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

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 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.

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.

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).

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

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

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.

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.2—NR.sup.1—COOR.sup.2 and wherein [B] has the structure: (i) —[CO—CH.sub.2—NR.sup.3]m-, or (ii) -[AA1-AA2]- or (iii) -(AA1-C0-CH.sub.2NR.sup.3)— or (iv) —(CO—CH.sub.2—NR.sup.3-AA1)- or (v) —(C0—CH.sub.2—NR.sup.4-AA1-AA3)-.