Applicants have developed an amplification system and methodology for IHC and ISH staining that utilizes “click chemistry” to covalently bind reporter molecules to tissue.

The phosphine transition metal complex of the present invention is represented by formula (1). ##STR00001##
Preferably, R.sup.1 and R.sup.6 are identical groups, R.sup.2 and R.sup.7 are identical groups, R.sup.3 and R.sup.8 are identical groups, R.sup.4 and R.sup.9 are identical groups, R.sup.5 and R.sup.10 are identical groups, and n and y are identical numbers. The phosphine transition metal complex is suitably obtained by reacting a phosphine derivative represented by formula (2) and a phosphine derivative represented by formula (3) with a salt of a transition metal of gold, copper or silver. ##STR00002##
See the description for the meanings of the symbols in each formula.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

The phosphine transition metal complex of the present invention is represented by formula (1).

##STR00001##

Preferably, R.sup.1 and R.sup.6 are identical groups, R.sup.2 and R.sup.7 are identical groups, R.sup.3 and R.sup.8 are identical groups, R.sup.4 and R.sup.9 are identical groups, R.sup.5 and R.sup.10 are identical groups, and n and y are identical numbers. The phosphine transition metal complex is suitably obtained by reacting a phosphine derivative represented by formula (2) and a phosphine derivative represented by formula (3) with a salt of a transition metal of gold, copper or silver.

##STR00002##

See the description for the meanings of the symbols in each formula.

Compounds represented by Formula (I) and (II) and salts thereof are described herein. The compounds or salts of Formula (I) and (II) may be used to treat senescence-associated diseases and disorders. ##STR00001##

Disclosed herein, inter alia, are compounds for binding STRAD pseudokinase and uses thereof.

Applicants have developed an amplification system and methodology for IHC and ISH staining that utilizes “click chemistry” to covalently bind reporter molecules to tissue.

There is provided a method for producing a 2,3-bisphosphinopyrazine derivative, the method comprising a first step of adding a base to a liquid comprising: 2,3-dihalogenopyrazine represented by the following general formula (1); a hydrogen-phosphine borane compound represented by the following general formula (2); and a deboranating agent, and allowing the resultant to react to thereby obtain the 2,3-bisphosphinopyrazine derivative represented by the following general formula (3). According to the present invention, a method for producing the industrially advantageous 2,3-bisphosphinopyrazine derivative can be provided. ##STR00001##

Dye and compositions to monitor the multistep protein aggregation process in both test tubes and live cells are provided. These dyes can detect misfolded protein oligomers and distinguish insoluble protein aggregates from misfolded oligomers. Applications of these dyes include measuring kinetics of protein aggregation, monitoring aggregation of specific proteins in intact live cells, monitoring aggregation of cellular proteome in intact live cells, and tracking the time course of protein aggregation in cells under stress conditions.

The aryl sulfonamide compounds of this invention have powerful and cell-type specific Bcl inhibitory activity. Selected compounds in this class promote apoptosis in senescent cells, and are being developed for treating senescent-related conditions. Selected compounds in this class promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.