Provided herein are compositions of carbonic anhydrase and inhibitors thereof for the treatment of subjects with certain conditions such as heart disease.

Provided herein are methods of using andrographolide, oridonin, isoliquiritigenin, and derivatives thereof to upregulate β-defensin 3 expression in humans and other veterinary animals. Upregulated β-defensin 3 expression is useful in a number of contexts including the prevention of infections, promotion of mucosal health, treatment of wounds, and the treatment of respiratory conditions.

The present invention relates to a composition comprising a compound of formula (I) wherein X is selected from the group consisting of S, Se, P, PO, SO, NR.sup.1, CR.sup.1, CR.sup.1R.sup.1 or C.sub.0-2-alkyl; Z is selected from the group consisting of hydrogen, a halogen, SR.sup.4, OR.sup.4, COR.sup.4 where R.sup.4 is a C.sub.1-12-alkyl; each R.sup.2 is independently selected from the group consisting of C.sub.1-6-alkyl, halogen, C.sub.3-8-cycloalkyl, OH, NH.sub.2, NHR.sup.1, N(R.sup.1).sub.2, O—C.sub.1-6-alkyl, O—C.sub.3-8-cycloalkyl, NH—C.sub.1-6-alkyl, NH—C.sub.3-8-cycloalkyl, S—C.sub.1-6-alkyl, S—C.sub.3-8-cycloalkyl, aryl, heteroaryl, aryloxy, heteroaryloxy, arylamino, heteroarylamino, arylalkyl, heteroarylalkyl, arylalkyloxy and heteroarylalkyloxy; d is selected from 0, 1, 2, and 3; each R.sup.3 is independently selected from the group consisting of C.sub.1-6-alkyl, halogen, C.sub.3-8-cycloalkyl, OH, NH.sub.2, NHR.sup.1, N(R.sup.1).sub.2, O—C.sub.1-6-alkyl, O—C.sub.3-8-cycloalkyl, NH—C.sub.1-6-alkyl, NH—C.sub.3-8-cycloalkyl, S—C.sub.1-6-alkyl, S-C3-8-cycloalkyl, aryl, heteroaryl, aryloxy, heteroaryloxy, arylamino, heteroarylamino, arylalkyl, heteroarylalkyl, arylalkyloxy and heteroarylalkyloxy; e is selected from 0, 1, 2, 3, and 4; R.sup.1 is selected from the group consisting of C.sub.1-6-alkyl, C.sub.3-8-cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl; R.sup.5 is N—(CHW)—N(Y.sup.1)(Y.sup.2)(Y.sup.3) or C═CH—(CHW)—N(Y.sup.1)(Y.sup.2)(Y.sup.3); each W is individually selected from the group consisting of linear or branched C.sub.1-6-alkyl or together with the nitrogen atom —N(Y.sup.1)(Y.sup.2)(Y.sup.3)— to which it is attached forms an optionally substituted nitrogen-containing heteroaryl or optionally substituted nitrogen-containing heterocyclyl together with Y.sup.1 where; Y.sup.1 is selected from the group consisting of C.sub.1-12-alkyl or together with the W and the nitrogen atom to which it is attached forms an optionally substituted nitrogen-containing heteroaryl or optionally substituted nitrogen-containing heterocyclyl; Y.sup.2 is selected from the group consisting of C.sub.1-12-alkyl; Y.sup.3 is selected from the group consisting of linear or branched C.sub.2-25-alkyl, linear or branched C.sub.2-25 alkenyl or linear or branched C.sub.2-25 alkynyl; where A is selected from any pharmaceutical relevant/acceptable anion/counterion; wherein if X is S and Z is a halogen then Y.sup.3 cannot be a C.sub.2-alkyl or a branched C.sub.3-alkyl; wherein if X is S and Z is hydrogen then Y.sup.3 cannot be C.sub.2-alkyl or linear or branched C.sub.5-alkyl. The invention also relates to anti-microbial composition fo

The present invention relates to a composition comprising a compound of formula (I) wherein X is selected from the group consisting of S, Se, P, PO, SO, NR.sup.1, CR.sup.1, CR.sup.1R.sup.1 or C.sub.0-2-alkyl; Z is selected from the group consisting of hydrogen, a halogen, SR.sup.4, OR.sup.4, COR.sup.4 where R.sup.4 is a C.sub.1-12-alkyl; each R.sup.2 is independently selected from the group consisting of C.sub.1-6-alkyl, halogen, C.sub.3-8-cycloalkyl, OH, NH.sub.2, NHR.sup.1, N(R.sup.1).sub.2, O—C.sub.1-6-alkyl, O—C.sub.3-8-cycloalkyl, NH—C.sub.1-6-alkyl, NH—C.sub.3-8-cycloalkyl, S—C.sub.1-6-alkyl, S—C.sub.3-8-cycloalkyl, aryl, heteroaryl, aryloxy, heteroaryloxy, arylamino, heteroarylamino, arylalkyl, heteroarylalkyl, arylalkyloxy and heteroarylalkyloxy; d is selected from 0, 1, 2, and 3; each R.sup.3 is independently selected from the group consisting of C.sub.1-6-alkyl, halogen, C.sub.3-8-cycloalkyl, OH, NH.sub.2, NHR.sup.1, N(R.sup.1).sub.2, O—C.sub.1-6-alkyl, O—C.sub.3-8-cycloalkyl, NH—C.sub.1-6-alkyl, NH—C.sub.3-8-cycloalkyl, S—C.sub.1-6-alkyl, S-C3-8-cycloalkyl, aryl, heteroaryl, aryloxy, heteroaryloxy, arylamino, heteroarylamino, arylalkyl, heteroarylalkyl, arylalkyloxy and heteroarylalkyloxy; e is selected from 0, 1, 2, 3, and 4; R.sup.1 is selected from the group consisting of C.sub.1-6-alkyl, C.sub.3-8-cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl; R.sup.5 is N—(CHW)—N(Y.sup.1)(Y.sup.2)(Y.sup.3) or C═CH—(CHW)—N(Y.sup.1)(Y.sup.2)(Y.sup.3); each W is individually selected from the group consisting of linear or branched C.sub.1-6-alkyl or together with the nitrogen atom —N(Y.sup.1)(Y.sup.2)(Y.sup.3)— to which it is attached forms an optionally substituted nitrogen-containing heteroaryl or optionally substituted nitrogen-containing heterocyclyl together with Y.sup.1 where; Y.sup.1 is selected from the group consisting of C.sub.1-12-alkyl or together with the W and the nitrogen atom to which it is attached forms an optionally substituted nitrogen-containing heteroaryl or optionally substituted nitrogen-containing heterocyclyl; Y.sup.2 is selected from the group consisting of C.sub.1-12-alkyl; Y.sup.3 is selected from the group consisting of linear or branched C.sub.2-25-alkyl, linear or branched C.sub.2-25 alkenyl or linear or branched C.sub.2-25 alkynyl; where A is selected from any pharmaceutical relevant/acceptable anion/counterion; wherein if X is S and Z is a halogen then Y.sup.3 cannot be a C.sub.2-alkyl or a branched C.sub.3-alkyl; wherein if X is S and Z is hydrogen then Y.sup.3 cannot be C.sub.2-alkyl or linear or branched C.sub.5-alkyl. The invention also relates to anti-microbial composition fo

Provided herein are pharmaceutical compositions, each comprising a pyrone compound, for example, a compound of Formula I, and a pharmaceutically acceptable excipient. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of an inflammatory, neurodegenerative, or immune-mediated disease (e.g., multiple sclerosis).

##STR00001##

Provided herein are pharmaceutical compositions, each comprising a pyrone compound, for example, a compound of Formula I, and a pharmaceutically acceptable excipient. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of an inflammatory, neurodegenerative, or immune-mediated disease (e.g., multiple sclerosis).

##STR00001##

Methods, compositions and kits for reducing renal tissue toxicity in a subject caused by a kidney damaging agent are provided. The methods comprise administering to the subject: (i) a kidney damaging agent; (ii) a PPARA activator; and (iii) an inhibitor of a cellular pathway selected from the group consisting of C/EBP, PPARG, ER stress, GLUT2 and SGLT1/2; or (i) a kidney damaging agent; (ii) a SGLT2 inhibitor; and (iii) a PPARA activator, a C/EBP inhibitor, a PPARG inhibitor, or an ER stress inhibitor.

Methods, compositions and kits for reducing renal tissue toxicity in a subject caused by a kidney damaging agent are provided. The methods comprise administering to the subject: (i) a kidney damaging agent; (ii) a PPARA activator; and (iii) an inhibitor of a cellular pathway selected from the group consisting of C/EBP, PPARG, ER stress, GLUT2 and SGLT1/2; or (i) a kidney damaging agent; (ii) a SGLT2 inhibitor; and (iii) a PPARA activator, a C/EBP inhibitor, a PPARG inhibitor, or an ER stress inhibitor.

Disclosed herein are methods for treating cancer comprising administering at least one immune checkpoint inhibitor and at least one Retinoic Acid Receptor or Retinoid X Receptor active agent.

Disclosed herein are methods for treating cancer comprising administering at least one immune checkpoint inhibitor and at least one Retinoic Acid Receptor or Retinoid X Receptor active agent.