Cardax Pharmaceuticals, Inc.

Hawaii Biotech, Inc.

Hawaii Biotechnology Group, Inc.

Cardax Pharma, Inc.

Sean O'Malley

Henry Lee Jackson

Samuel Fournier Lockwood

Geoff Nadolski

David G Watumull

Laura M Hix

Alan Thomas Johnson

Seong Jin Kim

Guan-Sheng Jiao

Paul G Grothaus

Dana E Davis

Compounds of Formula I are provided: Ris &#x2014;OR, m is an integer from 0 to 5, n is an integer from 0 to 2, each Ris independently selected from hydrogen, halogen, and alkyl, Ris selected from hydrogen, alkyl, cycloalkyl, aryl, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkyloxyalkyl, aralkyl, alkylaminoalkyl, dialkylaminoalkyl, aralkylaminoalkyl, and heterocycloalkyl, Ris an alkyl, each Ris independently hydrogen or alkyl, and each of R, R, R, and Ris independently optionally substituted. Compounds of Formula I are included in pharmaceutical compositions for the treatment of a subject exposed to atoxin.

Hydroxamic acids comprising pyrazole moiety and uses thereof

Compounds of formula I are provided: Ris an alkoxy or O(CH)X, p is an integer from 2 to 3 and X is OH, NH, or COH, m is an integer from 0 to 5, n is an integer from 0 to 5, each Ris independently selected from hydrogen, alkenyl, hydroxyalkyl, alkoxymethyl, heterocyclyl, hetereocyclylmethyl, amino, amido, hydroxamido, any of which may be optionally substituted with one or more of acyl, alkyl, alkoxy, hydroxyalkyl, or halogen, each Ris independently selected from hydrogen, halogen, alkyl, alkenyl, carboxy, hydroxymethyl, amido, and at least one of Rand Ris not hydrogen.

Hydroxamic acids and uses thereof

A method of controlling (e.g., influencing or affecting) connexin 43 expression in a subject may include administering to the subject an effective amount of a pharmaceutically acceptable formulation. In some embodiments, controlling connexin 43 expression in a subject may effectively treat cardiac arrhythmia and/or cancerous and pre-cancerous cells in a subject. The pharmaceutically acceptable formulation may include a synthetic analog or derivative of a carotenoid. The subject may be administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include an acyclic alkene including at least one substituent and/or a cyclic ring including at least one substituent. In some embodiments, a carotenoid analog or derivative may include at least one substituent.

[object Object]

A method of treating liver disease in a subject may include administering to the subject an effective amount of a pharmaceutically acceptable formulation. The pharmaceutically acceptable formulation may include a synthetic analog or derivative of a carotenoid. The subject may be administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include a cyclic ring including at least one substituent. In some embodiments, a cyclic ring of a carotenoid analog or derivative may include at least one substituent. The substituent may be coupled to the cyclic ring with an ester functionality.

Carotenoid ester analogs or derivatives for the inhibition and amelioration of liver disease

A method for inhibiting and/or ameliorating the occurrence of diseases in a human subject whereby a subject is administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative. In some embodiments, the administration of analogs or derivatives of carotenoids may inhibit and/or ameliorate the occurrence of diseases in subjects. In some embodiments, analogs or derivatives of carotenoids may be water-soluble and/or water dispersible. Maladies that may be treated with analogs or derivatives of carotenoids embodied herein may include diseases that provoke or trigger an inflammatory response. In an embodiment, asthma may be treated with analogs or derivatives of carotenoids embodied herein. In an embodiment, administering analogs or derivatives of carotenoids embodied herein to a subject may control or affect the bioavailability of eicosanoids. In an embodiment, atherosclerosis may be treated with analogs or derivatives of carotenoids embodied herein. In an embodiment, administering the analogs or derivatives of carotenoids embodied herein to a subject may control or affect the bioavailability of 5-LO-catalyzed eicosanoid metabolites. In an embodiment, 5-LO-catalyzed eicosanoid metabolites that may be controlled or affected by administering analogs or derivatives of carotenoids to a subject may include proinflammatory effector molecules (e.g., leukotrienes).

Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation

A method for inhibiting and/or ameliorating the occurrence of diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals in a subject whereby a subject is administered a carotenoid structural analog, either alone or in combination with another carotenoid analog, or co-antioxidant formulation. The analog or analog combination is administered such that the subject's risk of experiencing diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals may be thereby reduced. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of ischemia-reperfusion injury. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of liver disease. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of cancer. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of cardiac arrhythmia and/or sudden cardiac death. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of any disease that involves production of reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals. In one embodiment, a water-soluble and/or water-dispersible astaxanthin analog is particularly effective. This invention further includes pharmaceutical compositions comprising structural carotenoid analogs either alone or in combination.

Structural carotenoid analogs for the inhibition and amelioration of disease

A method for inhibiting and/or ameliorating the occurrence of diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals in a subject whereby a subject is administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The analog or derivative is administered such that the subject's risk of experiencing diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals may be thereby reduced. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of any disease that involves production of reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals. In some embodiments, the invention may include a chemical compound including an analog or derivative of a carotenoid. The carotenoid analog or derivative may be synthetic. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include an acyclic alkene including at least one substituent and/or a cyclic ring including at least one substituent. In some embodiments, a carotenoid analog or derivative may include at least one substituent. The substituent may enhance the solubility of the carotenoid analog or derivative such that the carotenoid analog or derivative at least partially dissolves in water.

Carotenoid analogs or derivatives for the inhibition and amelioration of disease

A method for inhibiting and/or ameliorating the occurrence of diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals in a subject whereby a subject is administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The analog or derivative is administered such that the subject's risk of experiencing diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals may be thereby reduced. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of any disease that involves production of reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals. In some embodiments, the invention may include a pharmaceutical composition including a carotenoid analog or derivative. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include a cyclic ring including at least one substituent. In some embodiments, a cyclic ring of a carotenoid analog or derivative may include at least one substituent. The substituent may be coupled to the cyclic ring with an ether functionality. In some embodiments, a pharmaceutical composition may include a biologically inactive carrier. The pharmaceutical composition may be adapted to be administered to a human subject.

Pharmaceutical compositions including carotenoid ether analogs or derivatives for the inhibition and amelioration of disease

A method for inhibiting and/or ameliorating the occurrence of diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals in a subject whereby a subject is administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The analog or derivative is administered such that the subject's risk of experiencing diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals may be thereby reduced. In some embodiments, the invention may include a chemical compound including an at least partially water soluble carotenoid analog or derivative. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include a cyclic ring including at least one substituent. The substituent may be coupled to the cyclic ring with an ether functionality.

Carotenoid ether analogs or derivatives for the inhibition and amelioration of disease

A method for inhibiting and/or ameliorating the occurrence of diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals in a subject whereby a subject is administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The analog or derivative is administered such that the subject's risk of experiencing diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals may be thereby reduced. In some embodiments, the invention may include a pharmaceutical composition including a carotenoid analog or derivative. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include a cyclic ring including at least one substituent. The substituent may be coupled to the cyclic ring with an ester functionality. The pharmaceutical composition may be adapted to be administered to a human subject.

Pharmaceutical compositions including carotenoid ester analogs or derivatives for the inhibition and amelioration of disease

A method of treating ischemic reperfusion injury in a subject. The method may include administering to the subject an effective amount of a pharmaceutically acceptable formulation. The pharmaceutically acceptable formulation may include a synthetic analog or derivative of a carotenoid. The subject may be administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include a cyclic ring including at least one substituent. In some embodiments, a cyclic ring of a carotenoid analog or derivative may include at least one substituent. The substituent may be coupled to the cyclic ring with an ester functionality.

Carotenoid ester analogs or derivatives for the inhibition and amelioration of ischemic reperfusion injury

A method for inhibiting and/or ameliorating the occurrence of diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals in a subject whereby a subject is administered a carotenoid structural analog, either alone or in combination with another carotenoid analog, or co-antioxidant formulation. The analog or analog combination is administered such that the subject's risk of experiencing diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals may be thereby reduced. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of ischemia-reperfusion injury, liver disease, cancer, cardiac arrhythmia and/or sudden cardiac death, and/or any disease that involves production of reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals. In one embodiment, a water-soluble and/or water-dispersible astaxanthin analog is particularly effective. This invention further includes pharmaceutical compositions comprising structural carotenoid analogs either alone or in combination.

An assay is disclosed for determining whether a test compound modulates the activity of an enzyme having a metallated active site. The assay method employs a comparison of the binding ability of the metallated and unmetallated forms of the enzyme to the test compound.

Growing community of inventors

Honolulu, HI, United States of America

Sean O'Malley