The present invention relates to immunoconjugates, compositions, methods and uses for treating brain tumors, especially glioma, by administration of a tumour necrosis factor alpha (TNFα) immunoconjugate.

The present invention provides compounds for use in the treatment of respiratory diseases of animals, especially Bovine or Swine Respiratory disease (BRD and SRD).

The present invention provides compounds for use in the treatment of respiratory diseases of animals, especially Bovine or Swine Respiratory disease (BRD and SRD).

Described herein is a multiplexed and high content screening assay using primary neurons for identifying small molecule modulators of neuronal mitochondrial mitostasis (MnMs). Also described is a high throughput screening assay using primary neurons for identifying small molecules that increase mitochondrial function, identified by measuring the electrochemical potential across the inner mitochondrial membrane and ATP generation. Most MnMs that increased mitochondrial content, length and/or health also increased mitochondrial function without altering neurite outgrowth. Some MnMs protect mitochondria in primary neurons from Aβ(1-42) toxicity, glutamate toxicity, increased oxidative stress and the toxic cellular environment associated with Alzheimer's disease. Some MnMs target mitochondria directly. An MnM also increases the synaptic activity of hippocampal neurons and is potent in vivo, increasing the respiration rate of brain mitochondria after administering the compound to mice. The MnMs were demonstrated to protect the mitochondrial population in neurons in an in vivo model of Alzheimer's Disease. Also described is a method for treating a patient suffering from a disorder characterized by dysfunction of neuronal mitostasis, comprising administering to the patient a therapeutically effective amount of a compound (MnM), or a pharmaceutically acceptable salt thereof.

Described herein is a multiplexed and high content screening assay using primary neurons for identifying small molecule modulators of neuronal mitochondrial mitostasis (MnMs). Also described is a high throughput screening assay using primary neurons for identifying small molecules that increase mitochondrial function, identified by measuring the electrochemical potential across the inner mitochondrial membrane and ATP generation. Most MnMs that increased mitochondrial content, length and/or health also increased mitochondrial function without altering neurite outgrowth. Some MnMs protect mitochondria in primary neurons from Aβ(1-42) toxicity, glutamate toxicity, increased oxidative stress and the toxic cellular environment associated with Alzheimer's disease. Some MnMs target mitochondria directly. An MnM also increases the synaptic activity of hippocampal neurons and is potent in vivo, increasing the respiration rate of brain mitochondria after administering the compound to mice. The MnMs were demonstrated to protect the mitochondrial population in neurons in an in vivo model of Alzheimer's Disease. Also described is a method for treating a patient suffering from a disorder characterized by dysfunction of neuronal mitostasis, comprising administering to the patient a therapeutically effective amount of a compound (MnM), or a pharmaceutically acceptable salt thereof.

The present invention relates to high doses of macitentan (INN), i.e. propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide or pharmaceutically acceptable salts, solvates, hydrates or morphological forms thereof for use in the treatment of pulmonary vascular disease and/or cardiac dysfunction in functional single ventricular heart disease patients, especially in Fontan-palliated patients. Moreover, the present invention relates to the use of high doses of macitentan for the manufacture of a medicament as well as to a method for the treatment of said diseases. Further, the present invention relates to a dosage regimen as well as to a combination of macitentan with one or more phosphodiesterase type 5 (PDE5) inhibitors, prostacyclin analogues, prostacyclin receptor agonists or soluble guanylate cyclase stimulators. Besides, the present invention relates to a pharmaceutical composition for the treatment of pulmonary vascular disease and/or cardiac dysfunction in functional single ventricular heart disease patients, especially in Fontan-palliated patients comprising a high dose of macitentan. Moreover, the present invention relates to the use of high doses aprocitentan for the same purpose.

The present invention relates to high doses of macitentan (INN), i.e. propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide or pharmaceutically acceptable salts, solvates, hydrates or morphological forms thereof for use in the treatment of pulmonary vascular disease and/or cardiac dysfunction in functional single ventricular heart disease patients, especially in Fontan-palliated patients. Moreover, the present invention relates to the use of high doses of macitentan for the manufacture of a medicament as well as to a method for the treatment of said diseases. Further, the present invention relates to a dosage regimen as well as to a combination of macitentan with one or more phosphodiesterase type 5 (PDE5) inhibitors, prostacyclin analogues, prostacyclin receptor agonists or soluble guanylate cyclase stimulators. Besides, the present invention relates to a pharmaceutical composition for the treatment of pulmonary vascular disease and/or cardiac dysfunction in functional single ventricular heart disease patients, especially in Fontan-palliated patients comprising a high dose of macitentan. Moreover, the present invention relates to the use of high doses aprocitentan for the same purpose.

The present disclosure relates to prodrugs, double prodrugs, derivatives and analogues of 3-(methylamino)-2-((methylamino)methyl)propane-1-thiol. The compounds of this disclosure also relate to ##STR00001##
The use of these compounds as radio— and chemo—protectors is also described.

The present application provides SOX9 inhibitor compounds and compositions and methods of use thereof. In certain aspects, the SOX9 inhibitor is a peptide comprising a portion of the SOX9 dimerization motif. In other aspects, the SOX9 inhibitor is a compound of the general formula I

##STR00001##

where one A is H and the other is:

##STR00002##

and the remaining substituents are as defined in the application.

Disclosed are a benzyl piperazine compound, a preparation method there for and an application thereof in an antivirus. The benzyl piperazine compound has a structure represented by the following general formula(I). It is proven by experiments that the benzyl piperazine compound not only has significant antiviral activity, but also has the advantages of low cytotoxicity, a high selectivity index and soon.

##STR00001##