The present invention pertains to methods of using certain 1-di-isopropyl-phosphinoylalkanes as described herein (DIPA-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds”) for the treatment of ocular discomfort that is caused by eye strain; eye surgery; an airborne irritant or pollutant that interacts with the eye surface; heat discomfort; extended wear of contact lenses; excessive exposure to the sun; asthenopia; conjunctivitis; or a dry eye syndrome. The present invention also pertains to pharmaceutical compositions comprising such compounds, and media contain those pharmaceutical compositions.

A fatty acid-like platinum (IV) prodrug is useful for treating cancer (e.g., ovarian cancer). The fatty acid-like platinum (IV) prodrug may be used in combination with a M1 macrophage.

Compounds and methods for treating, preventing, and ameliorating at least one of vascular oxidative stress, improve vascular functions and/or reduce hypertension, comprising administering to a subject a compound that targets mitochondrial CypD to inhibit vascular oxidative stress, improve vascular functions and/or reduce hypertension.

Tri-phenyl-phosphonium (TPP) is a non-toxic chemical moiety that functionally behaves as a mitochondrial targeting signaling in living cells. TPP-related compounds may be utilized to target mitochondria in cancer stem cells (CSC5), and may be used for treating and/or preventing tumor recurrence, metastasis, drug resistance, and/or radiotherapy resistance, as well as for anticancer therapies. Various TPP-related compounds validated for oxygen consumption inhibition (OCR), were non-toxic, and had little or no effect on ATP production in normal human fibroblasts. Yet these compounds selectively target adherent “bulk” cancer cells. These compounds also inhibit the propagation of CSCs in suspension. TPP-related compounds provide a novel chemical strategy for effectively targeting both i) “bulk” cancer cells and ii) CSCs, while specifically minimizing or avoiding off-target side-effects in normal cells, among other useful therapies.

Tri-phenyl-phosphonium (TPP) is a non-toxic chemical moiety that functionally behaves as a mitochondrial targeting signaling in living cells. TPP-related compounds may be utilized to target mitochondria in cancer stem cells (CSC5), and may be used for treating and/or preventing tumor recurrence, metastasis, drug resistance, and/or radiotherapy resistance, as well as for anticancer therapies. Various TPP-related compounds validated for oxygen consumption inhibition (OCR), were non-toxic, and had little or no effect on ATP production in normal human fibroblasts. Yet these compounds selectively target adherent “bulk” cancer cells. These compounds also inhibit the propagation of CSCs in suspension. TPP-related compounds provide a novel chemical strategy for effectively targeting both i) “bulk” cancer cells and ii) CSCs, while specifically minimizing or avoiding off-target side-effects in normal cells, among other useful therapies.

Tri-phenyl-phosphonium (TPP) is a non-toxic chemical moiety that functionally behaves as a mitochondrial targeting signaling in living cells. TPP-related compounds may be utilized to target mitochondria in cancer stem cells (CSC5), and may be used for treating and/or preventing tumor recurrence, metastasis, drug resistance, and/or radiotherapy resistance, as well as for anticancer therapies. Various TPP-related compounds validated for oxygen consumption inhibition (OCR), were non-toxic, and had little or no effect on ATP production in normal human fibroblasts. Yet these compounds selectively target adherent “bulk” cancer cells. These compounds also inhibit the propagation of CSCs in suspension. TPP-related compounds provide a novel chemical strategy for effectively targeting both i) “bulk” cancer cells and ii) CSCs, while specifically minimizing or avoiding off-target side-effects in normal cells, among other useful therapies.

Methods are provided of identifying a subject having impaired aldehyde dehydrogenase activity; and administering to the subject a compound comprising an isotopicaliy-modified polyunsaturated fatty acid, an isotopicaliy-modified polyunsaturated fatty acid ester, an isotopicaliy-modified polyunsaturated fatty acid thioester, an isotopicaliy-modified polyunsaturated fatty acid amide, a polyunsaturated fatty acid mimetic, or an isotopicaliy-modified polyunsaturated fatty acid pro-drug, the compound having an isotopic modification that reduces oxidation of the compound, thereby reducing production in the subject of substrate for aldehyde dehydrogenase. Some aspects provide coadministering an isotopicaliy-modified polyunsaturated fatty acid and an oxylipin.

Methods are provided of identifying a subject having impaired aldehyde dehydrogenase activity; and administering to the subject a compound comprising an isotopicaliy-modified polyunsaturated fatty acid, an isotopicaliy-modified polyunsaturated fatty acid ester, an isotopicaliy-modified polyunsaturated fatty acid thioester, an isotopicaliy-modified polyunsaturated fatty acid amide, a polyunsaturated fatty acid mimetic, or an isotopicaliy-modified polyunsaturated fatty acid pro-drug, the compound having an isotopic modification that reduces oxidation of the compound, thereby reducing production in the subject of substrate for aldehyde dehydrogenase. Some aspects provide coadministering an isotopicaliy-modified polyunsaturated fatty acid and an oxylipin.

Methods are provided of identifying a subject having impaired aldehyde dehydrogenase activity; and administering to the subject a compound comprising an isotopicaliy-modified polyunsaturated fatty acid, an isotopicaliy-modified polyunsaturated fatty acid ester, an isotopicaliy-modified polyunsaturated fatty acid thioester, an isotopicaliy-modified polyunsaturated fatty acid amide, a polyunsaturated fatty acid mimetic, or an isotopicaliy-modified polyunsaturated fatty acid pro-drug, the compound having an isotopic modification that reduces oxidation of the compound, thereby reducing production in the subject of substrate for aldehyde dehydrogenase. Some aspects provide coadministering an isotopicaliy-modified polyunsaturated fatty acid and an oxylipin.

The present disclosure relates to inhibitors of mitochondrial function. Methods of screening compounds for mitochondrial inhibition are disclosed. Also described are methods of using mitochondrial inhibitors called mitoriboscins—mitochondrial-based therapeutic compounds having anti-cancer and antibiotic properties—to prevent or treat cancer, bacterial infections, and pathogenic yeast, as well as methods of using mitochondrial inhibitors to provide anti-aging benefits. Specific mitoriboscin compounds and groups of mitoriboscins are also disclosed.