The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof: ##STR00001##

The present invention relates to novel compounds based on 3- ketocoumarins, which are useful as photoinitiators and sensitizer and to compositions thereof. More particularly, the novel compounds comprise a polyhydroxy polymeric core, which is chemically bonded to 3-ketocoumarin derivatives.

The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof: ##STR00001##

The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof: ##STR00001##

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.

Disclosed are XBP-1/IRE-1 inhibitors having formula disclosed herein. Methods of making and using these inhibitors for the treatment of cancer, in particular B cell cancers, are also disclosed. Also disclosed is a genetic XBP-1-knockout cancer mouse model.

Disclosed are XBP-1/IRE-1 inhibitors having formula disclosed herein. Methods of making and using these inhibitors for the treatment of cancer, in particular B cell cancers, are also disclosed. Also disclosed is a genetic XBP-1-knockout cancer mouse model.

Disclosed are XBP-1/IRE-1 inhibitors having formula disclosed herein. Methods of making and using these inhibitors for the treatment of cancer, in particular B cell cancers, are also disclosed. Also disclosed is a genetic XBP-1-knockout cancer mouse model.

Disclosed are XBP-1/IRE-1 inhibitors having formula disclosed herein. Methods of making and using these inhibitors for the treatment of cancer, in particular B cell cancers, are also disclosed. Also disclosed is a genetic XBP-1-knockout cancer mouse model.