Lysosomal acid lipase (LAL) substrates, assays for lysosomal acid lipase using the substrates, and methods for diagnosing diseases and conditions attributable to lysosomal acid lipase deficiency.

The present application describes process for preparing an ortho-allylated hydroxy aryl compounds such as compounds of Formula (I) by reacting an allylic alcohol with a hydroxy aryl compound in the presence of aluminum compound selected from alumina and aluminum alkoxides and in a non-protic solvent wherein at least one carbon atom ortho to the hydroxy group in the hydroxy aryl compound is unsubstituted. The present application also includes compounds of Formula (I).

##STR00001##

The sulfonium salt does not contain a toxic metal and exhibits higher cationic polymerization performance and crosslinking performance than a tetrakis(pentafluorophenyl)borate salt. The heat- or photo-acid generator contains the sulfonium salt. The sulfonium salt is formed of a sulfonium cation selected from a group represented by general formulas (1), (9), (10) and (11) described below and a gallate anion represented by formula (a). The heat- or photo-acid generator contains the sulfonium salt. The heat- or energy ray-curable composition contains the acid generator and a cationically polymerizable compound. A cured product can be obtained by curing the same. ##STR00001##

The sulfonium salt does not contain a toxic metal and exhibits higher cationic polymerization performance and crosslinking performance than a tetrakis(pentafluorophenyl)borate salt. The heat- or photo-acid generator contains the sulfonium salt. The sulfonium salt is formed of a sulfonium cation selected from a group represented by general formulas (1), (9), (10) and (11) described below and a gallate anion represented by formula (a). The heat- or photo-acid generator contains the sulfonium salt. The heat- or energy ray-curable composition contains the acid generator and a cationically polymerizable compound. A cured product can be obtained by curing the same. ##STR00001##

Activity-based probes that can be used to selectively identify and characterize enzymes that are involved in different phases of xenobiotic metabolism in a host and its microbiota population(s) are described. The activity-based probes described specifically label only their target active enzymes involved in xenobiotic metabolism and therefore provide a measurement of true protein functional activity rather than transcript or protein abundance. The activity-based probes also provide multimodal profiling of these active enzymes. Methods for preparing the activity based probes and exemplary methods for their use also are disclosed.

Activity-based probes that can be used to selectively identify and characterize enzymes that are involved in different phases of xenobiotic metabolism in a host and its microbiota population(s) are described. The activity-based probes described specifically label only their target active enzymes involved in xenobiotic metabolism and therefore provide a measurement of true protein functional activity rather than transcript or protein abundance. The activity-based probes also provide multimodal profiling of these active enzymes. Methods for preparing the activity based probes and exemplary methods for their use also are disclosed.

Compounds which directly inhibit IRE-1α activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response or with regulated IRE1-dependent decay (RIDD) and can be used as single agents or in combination therapies.

Compounds which directly inhibit IRE-1α activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response or with regulated IRE1-dependent decay (RIDD) and can be used as single agents or in combination therapies.

Detection of nitroxyl (HNO), the transient one-electron reduced form of nitric oxide, is a significant challenge owing to its high reactivity with biological thiols (rate constants as high as 10.sup.9M.sup.−1 s.sup.−1). Reported herein is a new thiol-based HNO-responsive trigger that can compete against reactive thiols for HNO. This process forms an N-hydroxysulfenamide intermediate which cyclizes to release a masked fluorophore leading to fluorescence enhancement. To ensure a rapid cyclization step, the disclosed design capitalizes on two established physical organic phenomena: the alpha-effect and the Thorpe-Ingold effect. Using this new trigger, NitroxylFluor was developed; a selective HNO-responsive fluorescent probe. Treatment of NitroxylFluor with an HNO donor results in a 16-fold turn-on. This probe also exhibits excellent selectivity over various reactive nitrogen, oxygen, and sulfur species and efficacy in the presence of thiols (e.g., glutathione in mM concentrations). Also, live cell imaging of HNO using NitroxylFluor was performed.

Detection of nitroxyl (HNO), the transient one-electron reduced form of nitric oxide, is a significant challenge owing to its high reactivity with biological thiols (rate constants as high as 10.sup.9M.sup.−1 s.sup.−1). Reported herein is a new thiol-based HNO-responsive trigger that can compete against reactive thiols for HNO. This process forms an N-hydroxysulfenamide intermediate which cyclizes to release a masked fluorophore leading to fluorescence enhancement. To ensure a rapid cyclization step, the disclosed design capitalizes on two established physical organic phenomena: the alpha-effect and the Thorpe-Ingold effect. Using this new trigger, NitroxylFluor was developed; a selective HNO-responsive fluorescent probe. Treatment of NitroxylFluor with an HNO donor results in a 16-fold turn-on. This probe also exhibits excellent selectivity over various reactive nitrogen, oxygen, and sulfur species and efficacy in the presence of thiols (e.g., glutathione in mM concentrations). Also, live cell imaging of HNO using NitroxylFluor was performed.