The present technology relates to novel cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools and/or biomarkers. The novel cannabinergic nitrate ester compounds provide medicaments useful in treating a variety of diseases and medical disorders.

The invention relates to novel small molecule compounds having a basic structure as depicted by formula (A), where in particular exemplary embodiments R.sup.1 is —OH, R.sup.2 is —NO.sub.2 and R.sup.3 is H, R.sup.4 and R.sup.5 are H, one of R.sup.6 and R.sup.7 is selected from H, —CONH.sub.2, and —CONR.sup.9.sub.2, and the other one is selected from —CONR.sup.9.sub.2 and —CONR.sup.11R.sup.9, wherein R.sup.9 and R.sup.11 are (possibly multiply) substituted alkyl and H or alkyl, respectively. The compounds of the invention inhibit the enzyme Catechol-O-methyltransferase (COMT) and exhibit a low off-target profile. The compounds are provided for use as a medicament, in particular for use in prevention or treatment of Parkinson's disease.

As described herein, chromosomal missegregations, chromosomal micronuclei, cytosolic DNA, and combinations thereof are indicative of metastatic cancer. Methods and compositions are described herein that are useful for detection and treatment of patients with chromosomal instabilities such as chromosomal missegregations, chromosomal micronuclei, cytosolic DNA, and combinations thereof. For example, some of the methods and compositions include use of kinesin-13 proteins such as Kif2b, MCAK/Kif2c, or KIF13A. The methods and compositions can also include inhibitors of STING, ENPP1, cGAS, NF-kB transcription factor p52, NF-kB transcription factor RelB, or any combination thereof. Methods are also described for identifying compounds that are effective for treatment of cancer, including metastatic cancer.

This invention relates to the use of nitroalkene derivatives for the treatment of neurodegenerative conditions in mammals in which neuroinflammation is a contributing factor, such as in amyotrophic lateral sclerosis (ALS).

Combination therapies for treating cancer comprising administration of a topoisomerase-1 inhibitor and a PARP inhibitor are provided. The topoisomerase-1 inhibitor can be delivered as a liposomal formulation that provides for prolonged accumulation of the topoisomerase-1 inhibitor within a tumor relative to outside of the tumor. Therapeutic benefit can thereby be obtained by delaying the administration of the PARP inhibitor after each administration of a liposomal irinotecan formulation until the accumulation of the topoisomerase inhibitor in the tumor is sufficiently greater than outside the tumor to result in increased efficacy of the PARP inhibitor and topoisomerase inhibitor within the tumor, while reducing the peripheral toxicity of the combination therapy. The therapies disclosed herein are useful in the treatment of human cancers with solid tumors, including cervical cancer.

Combination therapies for treating cancer comprising administration of a topoisomerase-1 inhibitor and a PARP inhibitor are provided. The topoisomerase-1 inhibitor can be delivered as a liposomal formulation that provides for prolonged accumulation of the topoisomerase-1 inhibitor within a tumor relative to outside of the tumor. Therapeutic benefit can thereby be obtained by delaying the administration of the PARP inhibitor after each administration of a liposomal irinotecan formulation until the accumulation of the topoisomerase inhibitor in the tumor is sufficiently greater than outside the tumor to result in increased efficacy of the PARP inhibitor and topoisomerase inhibitor within the tumor, while reducing the peripheral toxicity of the combination therapy. The therapies disclosed herein are useful in the treatment of human cancers with solid tumors, including cervical cancer.

A therapeutic or exercise putty includes a boronated silicone elastomer serving as the base ingredient or component and CBD or CBG oil or powder, DMSO, or CBD or CBG oil or powder together with DMSO, as a secondary ingredient mixed with the base putty. The inclusion of any one of the aforementioned secondary ingredients will reduce the pain and inflammation when the putty is used for hand rehabilitation or exercise by users and patients. Added side effects of reduced stress, tension or discomfort also contribute to a positive rehabilitation exercise experience that supports better user or patient health.

A method and device can alternately deliver high concentration of nitric oxide and oxygen-enriched air. A method of providing a therapeutic amount of nitric oxide to a mammal can include delivering one or more breaths of a therapeutic amount of nitric oxide to the mammal and delivering one or more breaths of an amount of oxygen-enriched air to the mammal immediately after the one or more breaths of the therapeutic amount of nitric oxide.

A method and device can alternately deliver high concentration of nitric oxide and oxygen-enriched air. A method of providing a therapeutic amount of nitric oxide to a mammal can include delivering one or more breaths of a therapeutic amount of nitric oxide to the mammal and delivering one or more breaths of an amount of oxygen-enriched air to the mammal immediately after the one or more breaths of the therapeutic amount of nitric oxide.

The invention provides methods and agents that modulate RelA activity. These methods and modulators of RelA activity can be used to treat cancer progression of basal-like breast cancer, such as triple-negative breast cancer.