The invention provides a pH-sensitive linker that can simultaneously bind metallic nanoparticles and one or more agents with various molecular size. The linker of the invention can deliver the agents into cells involved in disease processes or close to cells so that the agents can selectively target and effect on the cells. The target delivery provided by the linker of the invention can be used for example for disease sensing, imaging, drug delivery, and therapy.

The invention provides a pH-sensitive linker that can simultaneously bind metallic nanoparticles and one or more agents with various molecular size. The linker of the invention can deliver the agents into cells involved in disease processes or close to cells so that the agents can selectively target and effect on the cells. The target delivery provided by the linker of the invention can be used for example for disease sensing, imaging, drug delivery, and therapy.

This invention provides compounds of the formula (I):

##STR00001##

wherein Y.sup.1, Y.sup.2, Z, X.sup.1, X.sup.2, and W.sup.1 are defined in the specification. These compounds are useful in the treatment of tyrosine kinases, MAPK signaling pathway kinases and PI3K/AKT/mTor signaling pathway kinases-mediated diseases or conditions, such as neurodegeneration, neuroprotection, cancer, autoimmune as well as other diseases and conditions associated with the modulation of tyrosine kinases selected from FYN, FYN Y531F, FLT3, FLT3-ITD, BRK, ITK, FRK, BTK, BMX, SRC, FGR, YES1, LCK, HCK, RET, CSK, LYN, and ROS1; MAPK pathway kinases selected from ARAF, BRAF, CRAF, ERK1/2, MEK1, MEK2, MEK3, MEK4, MEK5, MEK6, and MEK7; and PI3K/AKT/mTor pathway kinases: selected from mTor, PI3K , PI3K , PI3K , and PI3K .

This invention provides compounds of the formula (I):

##STR00001##

wherein Y.sup.1, Y.sup.2, Z, X.sup.1, X.sup.2, and W.sup.1 are defined in the specification. These compounds are useful in the treatment of tyrosine kinases, MAPK signaling pathway kinases and PI3K/AKT/mTor signaling pathway kinases-mediated diseases or conditions, such as neurodegeneration, neuroprotection, cancer, autoimmune as well as other diseases and conditions associated with the modulation of tyrosine kinases selected from FYN, FYN Y531F, FLT3, FLT3-ITD, BRK, ITK, FRK, BTK, BMX, SRC, FGR, YES1, LCK, HCK, RET, CSK, LYN, and ROS1; MAPK pathway kinases selected from ARAF, BRAF, CRAF, ERK1/2, MEK1, MEK2, MEK3, MEK4, MEK5, MEK6, and MEK7; and PI3K/AKT/mTor pathway kinases: selected from mTor, PI3K , PI3K , PI3K , and PI3K .

The present invention relates to a pharmaceutical formulations and compositions comprising cholinergic agonist agents such as pilocarpine-R-(+)-lipoate or its salt, solvate, or hydrate thereof for oral administration with improved compliance, safety, and bioavailability. It further discloses methods of preparing the formulations and its use for the treatment of xerostomia, dry mouth and Sjogren's syndrome.

Described herein are compositions and methods for the treatment or prevention of ocular surface disorders including meibomian gland dysfunction, blepharitis, dry eye disease and other inflammatory and/or infectious diseases of the anterior surface of the eye(s). Said compositions and methods comprise keratolytic conjugates which demonstrate keratolytic activity, and anti-inflammatory or other desirable activities. Topical administration of said compositions to the eyelid margin or surrounding areas provides therapeutic benefit to patients suffering from ocular surface disorders.

Described herein are compositions and methods for the treatment or prevention of ocular surface disorders including meibomian gland dysfunction, blepharitis, dry eye disease and other inflammatory and/or infectious diseases of the anterior surface of the eye(s). Said compositions and methods comprise keratolytic conjugates which demonstrate keratolytic activity, and anti-inflammatory or other desirable activities. Topical administration of said compositions to the eyelid margin or surrounding areas provides therapeutic benefit to patients suffering from ocular surface disorders.

Novel compounds of N-Lipoic-amino acid, N-Lipoic-peptides and their derivatives are described. Also described are compositions and method of compositions containing the derivatives of the amino acids or peptides, and their uses including treating and preventing dermatological or cosmetic conditions or other disorders of the cutaneous system. Compositions and methods of using the compositions for skin lightening and cosmetics are also disclosed.

Novel compounds of N-Lipoic-amino acid, N-Lipoic-peptides and their derivatives are described. Also described are compositions and method of compositions containing the derivatives of the amino acids or peptides, and their uses including treating and preventing dermatological or cosmetic conditions or other disorders of the cutaneous system. Compositions and methods of using the compositions for skin lightening and cosmetics are also disclosed.

A series of multicoordinating and multifunctional ligands optimized for the surface-functionalization of luminescent quantum dots (QDs) and gold nanoparticles (AuNPs) alike is disclosed. An L-aspartic acid precursor is modified with functionality, through simple peptide coupling chemistry, one or two lipoic acid (LA) groups and poly(ethylene glycol) (PEG) moieties in the same ligand. These ligands were combined with a new photoligation strategy to yield hydrophilic and reactive QDs that are colloidally stable over a broad range of conditions, including storage at nanomolar concentration and under ambient conditions.