The present invention is drawn to the use of Minaprine dihydrochloride and analogs thereof, for reducing tumor growth when administered to a patient suffering from cancer.

Provided herein are compounds, enzyme substrates, compositions, kits, uses, and methods for detecting the presence or absence of a caspase enzyme, measuring the activity of a caspase enzyme, or detecting the presence or absence of apoptosis. The detection or measurement can occur through intracellular cleavage of a compound or enzyme substrate, which can lead to an increase in fluorescence, e.g., in the violet or red channel, through liberation of a nucleic acid binding dye from a peptide, such as liberation of a DNA-binding dye from a negatively charged peptide comprising a sequence recognized and cleaved by a caspase.

An object of the present invention is to provide novel apoptosis inhibitors and therapeutic agents for inner ear hearing impairment. As a pharmaceutical agent for this purpose, biguanide compounds represented by the following structural formula (I) or a rapamycin derivative represented by the following structural formula (II) as an active ingredient is provided: ##STR00001##
wherein R.sup.1 to R.sup.7 are each independently selected from a hydrogen atom, a halogen atom, or a C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a C.sub.6-10 aryl group, a 5- or 6-membered heteroaryl group, or a 5- or 6-membered non-aromatic heterocyclic group, each of which may have a substituent selected from a halogen atom, a cyano group, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group, a C.sub.1-6 alkoxy carbonyl group, a C.sub.3-8 cycloalkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, and a phenyl group; ##STR00002##
wherein R.sub.1 is a C.sub.1-6 alkyl or a C.sub.3-6 alkynyl, R.sub.2 is H, CH2-OH or CH.sub.2CH.sub.2OH, and X is O, (H, H) or (H, OH).

Synthetic fragment antigen-binding (Fab) antibodies are disclosed that bind to an N-terminal activation site of BCL-2-associated X-protein (BAX) and inhibit BAX activation. Also disclosed are methods of using the Fabs for measuring inactive monomeric BAX levels, screening for small molecules that bind to an N-terminal activation site of BAX, inhibiting apoptotic cell death, and predicting the ability of a cancer therapy to promote apoptotic cell death.

This disclosure provides therapeutic methods for treating cancer including combination therapy with a multimeric anti-DR5 antibody and a chemotherapeutic agent, e.g., a type I topoisomerase inhibitor, a nucleoside analog, or a pro-apoptotic agent, e.g., a BCL-2 inhibitor.

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I): ##STR00001##
including stereoisomers, salts and tautomers thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, L.sup.1, L.sup.2, L.sup.3, L.sup.4, M, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

The present invention relates to a method for labeling or targeting cells whose plasma membrane has lost integrity, such as dead cells, such as for discriminating between live cells and cells whose plasma membrane has lost integrity; to an embodiment of the method for determining one or more values of one or more parameters of cells of a biological sample; to use of the method in an assay for screening drugs for therapy such as cancer therapy; to use of the method to monitor and/or determine the effectiveness of a therapy; to an assay kit; to a complex; to the complex for use as a medicament; to the complex for use in treatment of cancer(s) and/or plaque(s) and/or regeneration and/or supporting the immune system; and, to a dead cell.

The present invention relates to a method for detecting cell death using a luminescent compound; to the luminescent compounds for particular uses; to a kit comprising said compounds and to a protein. The method is applicable for detecting cell death, essentially regardless of the mechanism through which cell death occurred or is occurring and is therefore not limited e.g. to detecting cell death resulting from only one mechanism selected from apoptosis and necrosis.

Provided herein are methods and assays for isolating and culturing seborrheic keratosis cells ex vivo. Also provided herein are screening assays using cultured seborrheic keratosis cells and methods for treating seborrheic keratosis in a subject.

Provided herein are methods and compositions relating to libraries of optimized antibodies having nucleic acids encoding for an antibody comprising modified sequences. Libraries described herein include variegated libraries comprising nucleic acids each encoding for a predetermined variant of at least one predetermined reference nucleic acid sequence. Further described herein are protein libraries generated when the nucleic acid libraries are translated. Further described herein are cell libraries expressing variegated nucleic acid libraries described herein.