The present invention is directed to compositions and methods for the treatment of cancers, particularly cancers of epithelial origin. Therapy with a plurality of nutraceutical, non-chemotherapeutic and chemotherapeutic agents, that together target a plurality of cancer-supportive processes in a patient are disclosed. Among other things, the present invention encompasses the insight that redundant targeting of multiple such pathways provides effective treatment of various cancer, including late-stage cancers, metastasized cancers, and/or cancers that have failed treatment with traditional chemotherapy and/or other therapeutic modalities.

The present invention is directed to compositions and methods for the treatment of cancers, particularly cancers of epithelial origin. Therapy with a plurality of nutraceutical, non-chemotherapeutic and chemotherapeutic agents, that together target a plurality of cancer-supportive processes in a patient are disclosed. Among other things, the present invention encompasses the insight that redundant targeting of multiple such pathways provides effective treatment of various cancer, including late-stage cancers, metastasized cancers, and/or cancers that have failed treatment with traditional chemotherapy and/or other therapeutic modalities.

The present invention is directed to compositions and methods for the treatment of cancers, particularly cancers of epithelial origin. Therapy with a plurality of nutraceutical, non-chemotherapeutic and chemotherapeutic agents, that together target a plurality of cancer-supportive processes in a patient are disclosed. Among other things, the present invention encompasses the insight that redundant targeting of multiple such pathways provides effective treatment of various cancer, including late-stage cancers, metastasized cancers, and/or cancers that have failed treatment with traditional chemotherapy and/or other therapeutic modalities.

The present invention relates to a pharmaceutical composition comprising a cyclotide and a ligand of the kappa opioid receptor (the kOR), or a combination thereof, for use in treating Multiple Sclerosis (MS), in remyelination, in improving CNS lesions, in preventing or reducing demyelination and/or CNS lesions, and/or in treating pain, in particular neuropathic pain and/or pain resulting from/coming along with MS. The present invention further relates to a combination of a cyclotide and a ligand of the kOR and to a pharmaceutical composition comprising said combination. The present invention further relates to a use of a cyclotide for reducing adverse effects of a ligand of the kOR and/or for increasing the potency and/or efficacy of a ligand of the kOR. Further, the present invention relates to a kit comprising a cyclotide and a ligand of the kOR. The present invention further relates to a pharmaceutical composition as part of a kit, wherein a comprised cyclotide and ligand of the kOR are for use in treating MS and related diseases and/or symptoms. The present invention further relates to a kit comprising a pharmaceutical composition comprising a cyclotide and a ligand of the kOR, wherein said pharmaceutical composition and/or said cyclotide and ligand of the kOR is/are for use in treating MS and related diseases and/or symptoms. The invention further relates to (a) novel Viola-type cyclotide(s).

The present invention relates to a pharmaceutical composition comprising a cyclotide and a ligand of the kappa opioid receptor (the kOR), or a combination thereof, for use in treating Multiple Sclerosis (MS), in remyelination, in improving CNS lesions, in preventing or reducing demyelination and/or CNS lesions, and/or in treating pain, in particular neuropathic pain and/or pain resulting from/coming along with MS. The present invention further relates to a combination of a cyclotide and a ligand of the kOR and to a pharmaceutical composition comprising said combination. The present invention further relates to a use of a cyclotide for reducing adverse effects of a ligand of the kOR and/or for increasing the potency and/or efficacy of a ligand of the kOR. Further, the present invention relates to a kit comprising a cyclotide and a ligand of the kOR. The present invention further relates to a pharmaceutical composition as part of a kit, wherein a comprised cyclotide and ligand of the kOR are for use in treating MS and related diseases and/or symptoms. The present invention further relates to a kit comprising a pharmaceutical composition comprising a cyclotide and a ligand of the kOR, wherein said pharmaceutical composition and/or said cyclotide and ligand of the kOR is/are for use in treating MS and related diseases and/or symptoms. The invention further relates to (a) novel Viola-type cyclotide(s).

The present invention relates to a pharmaceutical composition comprising a cyclotide and a ligand of the kappa opioid receptor (the kOR), or a combination thereof, for use in treating Multiple Sclerosis (MS), in remyelination, in improving CNS lesions, in preventing or reducing demyelination and/or CNS lesions, and/or in treating pain, in particular neuropathic pain and/or pain resulting from/coming along with MS. The present invention further relates to a combination of a cyclotide and a ligand of the kOR and to a pharmaceutical composition comprising said combination. The present invention further relates to a use of a cyclotide for reducing adverse effects of a ligand of the kOR and/or for increasing the potency and/or efficacy of a ligand of the kOR. Further, the present invention relates to a kit comprising a cyclotide and a ligand of the kOR. The present invention further relates to a pharmaceutical composition as part of a kit, wherein a comprised cyclotide and ligand of the kOR are for use in treating MS and related diseases and/or symptoms. The present invention further relates to a kit comprising a pharmaceutical composition comprising a cyclotide and a ligand of the kOR, wherein said pharmaceutical composition and/or said cyclotide and ligand of the kOR is/are for use in treating MS and related diseases and/or symptoms. The invention further relates to (a) novel Viola-type cyclotide(s).

The present disclosure relates to, among other things, compounds and methods for treating neuropathic pain, ocular pain, ocular inflammation, and/or dry eye and methods of detecting mutations in specific G-protein coupled receptors, such as missense mutations, and determining the extent to which these mutations alter the pharmacological response of the G-protein coupled receptor.

The present invention relates to peptide ligands of the melanocortin receptors, in particular the melancortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as insulin resistance.

The present invention relates to peptide ligands of the melanocortin receptors, in particular the melancortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as insulin resistance.

The present disclosure provides POZ derivatives having a range of active functional groups allowing conjugation of POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives. In one embodiment, the POZ derivative is a terminally activated monofunctional POZ derivative.