Abstract: Provided herein is a compound having a structure of Formula (I): (Formula (I)) wherein: D is S, O or an ester; p is 1 to 6; L1 and/or L2 are independently linear or branched C1-C30 alkyl, optionally having one or more C?C double bonds of E or Z geometry; and wherein: if D is S then L1 and/or L2 are unsubstituted or substituted with one or more S; and if D is O or an ester, then L1 and/or L2 are substituted with one more S. The compound may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acid. Further provided are methods for making the compound.

Abstract: The present invention provides a novel compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof, a preparation method thereof, and an antibiotic composition comprising the same. The novel compound of the present invention having excellent antimicrobial activity is very useful for preventing and treating a bacterial infection.

Abstract: Disclosed herein is a lipid having a net charge at physiological pH, and being covalently attached to a lipid moiety. The lipid moiety comprises a hydrocarbon structure having two or more linked hydrocarbon chains, optionally having cis or trans C?C, at least one of said chains being covalently attached to the head group optionally via the linker region. The hydrocarbon chains are bonded to one another at a branch point at an internal carbon of the chain attached to the linker region, which branch point comprises a functional group having an electronegative atom. The hydrocarbon chains each have between 1 and 40 carbon atoms, wherein the hydrocarbon structure in total comprises between 10 and 150 carbon atoms. Advantageously, the hydrocarbon structure may assume a generally flared shape for enhanced delivery of cargo molecules. Further provided are delivery vehicles comprising the lipids.

Abstract: The application relates to a lipid conjugate of formula M-X1-L wherein M is a molecule of interest such as a drug moiety; X1 is a linker group such as ester, ether or carbamate; and L is a lipid scaffold represented by formula (IId): -L1-[L2(H)(X2R)]n-L3-[L4(H)(X2R)]p-L5-L6 and wherein L comprises 5 to 40 carbon atoms and 0 to 2 carbon-carbon double bonds. The lipid conjugate can p be formulated in a drug delivery vehicle such as a lipid nanoparticle (LNP).

Abstract: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-dimethylaminomethyl-[1-3]-dioxolane by screening for an effect of the agent on the liver of a model subject.

Abstract: This invention provides lipid-linked prodrugs having structures as set out herein. Uses of such lipid-linked prodrug compounds for treatment of various indications, and methods for making and using lipid-linked prodrugs are also provided.

Abstract: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-dimethylaminomethyl-[1-3]-dioxolane by screening for an effect of the agent on the liver of a model subject.

Abstract: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract: This invention provides lipid-linked prodrugs having structures as set out herein. Uses of such lipid-linked prodrug compounds for treatment of various indications, and methods for making and using lipid-linked prodrugs are also provided.

Abstract: Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Abstract: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-dimethylaminomethyl-[1-3]-dioxolane by screening for an effect of the agent on the liver of a model subject.

Abstract: Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Abstract: The invention relates to a method for producing a hydrazine of general formula (I) and the pharmaceutically acceptable salts thereof from an amine of formula (II), characterised in that said method uses a urea of formula (III) as a synthesis intermediate.

Abstract: Novel compounds, particularly derivatives of boroarginine, boroornithine and borolysine that selectively modulate, regulate, and/or inhibit enteropeptidase. Compositions, particularly pharmaceutical compositions, as well as methods to treat excess weight, obesity and diseases associated with an abnormal fat metabolism.

Abstract: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-dimethylaminomethyl-[1-3]-dioxolane by screening for an effect of the agent on the liver of a model subject.

Abstract: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract: The invention relates to a method for producing a hydrazine of general formula (I) and the pharmaceutically acceptable salts thereof from an amine of formula (II), characterised in that said method uses a urea of formula (III) as a synthesis intermediate.

Abstract: A method of treating a lysosomal storage disease comprises administering a pyrimethamine derivative to a subject in need thereof.

Abstract: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract: Novel compounds selected from 2-(3-aminoaryl)amino-4-aryl-thiazoles of formula (I) that selectively modulate, regulate, and/or inhibit signal transductions mediated by certain native and/or mutant tyrosine kinases implicated in a variety of human and animal diseases such as cell proliferative metabolic, allergic and degenerative disorders. More particularly, these compounds are potent and selective c-kit inhibitors.