A61K31/06

METHODS AND COMPOSITIONS FOR TREATMENT OF BRAF MUTANT CANCERS
20200009138 · 2020-01-09 ·

The present invention provides various compositions and methods useful for the treatment of BRAF-mutant tumors, such as BRAF.sup.V600E-mutant tumors. In some embodiments such methods involve administration of three active agentsa RAF inhibitor, a MEK inhibitor, and an ERK inhibitor. The present invention also provides novel intermittent dosing regimens for these three active agents that maintain maximal anti-tumor efficacy while also minimizing toxicity.

NANOPARTICLES FOR MITOCHONDRIAL TRAFFICKING OF AGENTS
20200003782 · 2020-01-02 ·

Nanoparticles include a core, a hydrophilic layer around the core, and one or more mitochondrial targeting moieties, and may optionally include one or more contrast agents or one or more therapeutic agents. For effective mitochondrial targeting the nanoparticles have a diameter of about 200 nm or less or have a zeta potential of about 0 mV or more.

NANOPARTICLES FOR MITOCHONDRIAL TRAFFICKING OF AGENTS
20200003782 · 2020-01-02 ·

Nanoparticles include a core, a hydrophilic layer around the core, and one or more mitochondrial targeting moieties, and may optionally include one or more contrast agents or one or more therapeutic agents. For effective mitochondrial targeting the nanoparticles have a diameter of about 200 nm or less or have a zeta potential of about 0 mV or more.

2,4-dinitrophenol formulations and methods using same

The present invention includes a low dose and sustained release formulation of a mitochondrial uncoupling agent The compositions of the invention are useful for preventing or treating a disease or disorder, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, insulin resistance and/or diabetes, in a subject in need thereof.

2,4-dinitrophenol formulations and methods using same

The present invention includes a low dose and sustained release formulation of a mitochondrial uncoupling agent The compositions of the invention are useful for preventing or treating a disease or disorder, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, insulin resistance and/or diabetes, in a subject in need thereof.

Sensitization of cancer cells to differentiation therapy with mitochondrial uncoupler niclosamide ethanolamine

Methods are provided for the treatment of cancer by administering a mitochondrial uncoupler in a dose effective to increase differentiation of the cancer cells, which may be provided in a combination with a retinoic acid to differentiate the cancer cells. The effect on the targeted cancer cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used. The cancer may be resistant to retinoic acid.

Sensitization of cancer cells to differentiation therapy with mitochondrial uncoupler niclosamide ethanolamine

Methods are provided for the treatment of cancer by administering a mitochondrial uncoupler in a dose effective to increase differentiation of the cancer cells, which may be provided in a combination with a retinoic acid to differentiate the cancer cells. The effect on the targeted cancer cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used. The cancer may be resistant to retinoic acid.

Prostaglandin and prostamide drug delivery systems and intraocular therapeutic uses thereof

Biocompatible, bioerodible implants and microspheres include latanoprost and a biodegradable polymer effective, when placed intraocular (such as into the subtenon space) to treat glaucoma.

Anthelmintic compounds

The present invention relates to novel anthelmintic compounds of formula (I) below: ##STR00001##
wherein Y and Z are independently a bicyclic carbocyclic or a bicyclic heterocyclic group, or one of Y or Z is a bicyclic carbocyclic or a bicyclic heterocyclic group and the other of Y or Z is alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclyl or heteroaryl, and variables X.sub.1, X.sub.6, X.sub.8, Q.sub.1, Q.sub.2, Q.sub.3, Q.sub.4, Q.sub.5, Q.sub.6, Ring A, Ring B, W, W, R.sub.2, R.sub.3, R, R, m, n and q are as defined herein. The invention also provides for veterinary compositions comprising the anthelmintic compounds of the invention, and their uses for the treatment and prevention of parasitic infections in animals.

Anthelmintic compounds

The present invention relates to novel anthelmintic compounds of formula (I) below: ##STR00001##
wherein Y and Z are independently a bicyclic carbocyclic or a bicyclic heterocyclic group, or one of Y or Z is a bicyclic carbocyclic or a bicyclic heterocyclic group and the other of Y or Z is alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclyl or heteroaryl, and variables X.sub.1, X.sub.6, X.sub.8, Q.sub.1, Q.sub.2, Q.sub.3, Q.sub.4, Q.sub.5, Q.sub.6, Ring A, Ring B, W, W, R.sub.2, R.sub.3, R, R, m, n and q are as defined herein. The invention also provides for veterinary compositions comprising the anthelmintic compounds of the invention, and their uses for the treatment and prevention of parasitic infections in animals.