Abstract: This disclosure is directed to methods for treating an inflammatory disorder, comprising administering to a patient suffering from the disorder an effective amount of an inhibitor of an enzyme that regulates the S-palmitoylation of a pro-inflammatory transcription factor.

Abstract: A method for determining activity of an acyl transferase enzyme, the method comprising: (i) preparing a reaction mixture comprising: (a) an acyl transferase enzyme, (b) a peptide substrate bound to a fluorophore, wherein the substrate is a cysteine-containing oligopeptide of 5-25 amino acids in length, (c) an acyl-CoA, and (d) a detergent comprising micelles, wherein the acyl transferase enzyme mediates acylation on a cysteine of said peptide substrate to result in association of the peptide with micelles of the detergent with resultant increase in fluorescence polarization; and (ii) measuring fluorescent signal of the reaction mixture; wherein an increase in fluorescence polarization of the reaction mixture compared to fluorescence polarization of a control reaction indicates acyl transferase activity of the acyl transferase enzyme. The above assay method may also be used for screening compounds for their ability to act as inhibitors of an acyl transferase enzyme.

Abstract: The present disclosure is directed to a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a TiPARP agonist, wherein the TiPARP agonist may be, for example, a tamoxifen compound (e.g., tamoxifen or derivative thereof), flavone or derivative thereof, isoflavone or derivative thereof, diindolylmethane compound, or chlorinated dibenzo-p-dioxin (CDBD) compound or derivative thereof. The cancer may be associated with elevated expression of HIF-1? and may be selected from, for example, breast cancer, colon cancer, lung cancer, skin cancer, brain cancer, blood cancer, cervical cancer, liver cancer, prostate carcinoma, pancreas carcinoma, gastric carcinoma, ovarian carcinoma, renal cell carcinoma, mesothelioma, and melanoma. The cancer may, in some embodiments, exclude breast cancer.

Abstract: This disclosure demonstrates that inhibition of Sirt5 can suppress malignant transformation of cells. Therefore, methods of treating cancer based on inhibition of Sirt5 are disclosed.

Abstract: A compound useful as a Sirt2 or Sirt5 inhibitor having the formula (1) wherein: R1 is a hydrocarbon group having at least two carbon atoms connected by carbon-carbon bonds, wherein said hydrocarbon group is optionally endcapped by a neutral or anionic oxygen-containing group; R2a, R2b, and R2c are independently selected from hydrogen atom and hydrocarbon groups; X0, X1, X2, and X3 are independently selected from —(CH2)n—, —NR5—, —O—, —S—, and a bond, wherein n represents 1, 2, or 3, provided that at least one of X0-X3 is —(CH2)n—; and R3 and R4 are independently selected from the group consisting of hydrogen atom, hydrocarbon groups, biological groups, and protecting groups. Also described are pharmaceutical compositions of the inhibiting compounds, and methods of treatment by administration of the inhibiting compounds.

Abstract: This disclosure demonstrates that inhibition of Sirt5 can suppress malignant transformation of cells. Therefore, methods of treating cancer based on inhibition of Sirt5 are disclosed.

Abstract: This disclosure demonstrates that inhibition of Sirt5 can suppress malignant transformation of cells. Therefore, methods of treating cancer based on inhibition of Sirt5 are disclosed.

Abstract: Method for identifying a modulator of Sirt6, PfSir2a, or Sirt7 deacylase activity, wherein a fatty-acylated substrate containing an acyl-lysine moiety and an indicator moiety is contacted with Sirt6, PfSir2a, or Sirt7 in the presence of a candidate compound under conditions for Sirt6, PfSir2a, or Sirt7 to deacylate the substrate, wherein the acyl is a hydrophobic fatty acyl group containing a hydrocarbon group having at least three carbon atoms connected by carbon-carbon bonds; contacting the deacylated substrate with a cleavage agent that cleaves the linkage between the lysine and indicator moiety to generate a detectable signal; and correlating a quantified Sirt6, PfSir2a, or Sirt7 deacylase activity therefrom. Modulating compounds of Sirt6, PfSir2a, or Sirt7 deacylase activity are also described, as are pharmaceutical compositions thereof, methods of treatment by administration of the modulating compounds, and kits for practicing the method.

Abstract: Sirt5, a mitochondrial Sirtuin, has been identified herein as an efficient demalonylase and desuccinylase. Disclosed herein are assays to identify Sirt5 modulators based on this robust enzymatic activity. Sirt5-specific modulators can be used study the biological function of Sirt5 and to target Sirt5 activities in treating human diseases.

Abstract: The present disclosure provides NAD analogs of the formula: wherein R1, n, and X1 are defined herein, useful for the identification of PARP target proteins and the amino acid sequence wherein the ribose group is attached to the target protein. Also, provided herein are methods of identifying target protein and amino acid sequences. Additionally, the present disclosure provides methods of identifying DNA sequences associated with specific chromatin proteins.

Abstract: The instant application describes novel compounds that modulate (in particular, inhibit) Sirt2, with structures according to Formulas (1) and (2) provided herein. The invention is also directed to pharmaceutical compositions thereof, methods of treatment (i.e., cancer and neurodegenerative disease) by administration of the modulating compounds, assay methods for finding modulators of Sirt2, and kits for practicing the assay method.

Abstract: The present disclosure provides NAD analogs of the formula: wherein R1, n, and X1 are defined herein, useful for the identification of PARP target proteins and the amino acid sequence wherein the ribose group is attached to the target protein. Also, provided herein are methods of identifying target protein and amino acid sequences. Additionally, the present disclosure provides methods of identifying DNA sequences associated with specific chromatin proteins.

Abstract: The instant application describes novel compounds that modulate (in particular, inhibit) Sirt2, with structures according to Formulas (1) and (2) provided herein. The invention is also directed to pharmaceutical compositions thereof, methods of treatment (i.e., cancer and neurodegenerative disease) by administration of the modulating compounds, assay methods for finding modulators of Sirt2, and kits for practicing the assay method.

Abstract: The instant application describes novel compounds that modulate (in particular, inhibit) Sirt2 , with structures according to Formulas (1) and (2) provided herein. The invention is also directed to pharmaceutical compositions thereof, methods of treatment (i.e., cancer and neurodegenerative disease) by administration of the modulating compounds, assay methods for finding modulators of Sirt2 , and kits for practicing the assay method.

Abstract: Method for identifying a modulator of Sirt6, PfSir2a, or Sirt7 deacylase activity, wherein a fatty-acylated substrate containing an acyl-lysine moiety and an indicator moiety is contacted with Sirt6, PfSir2a, or Sirt7 in the presence of a candidate compound under conditions for Sirt6, PfSir2a, or Sirt7 to deacylate the substrate, wherein the acyl is a hydrophobic fatty acyl group containing a hydrocarbon group having at least three carbon atoms connected by carbon-carbon bonds; contacting the deacylated substrate with a cleavage agent that cleaves the linkage between the lysine and indicator moiety to generate a detectable signal; and correlating a quantified Sirt6, PfSir2a, or Sirt7 deacylase activity therefrom. Modulating compounds of Sirt6, PfSir2a, or Sirt7 deacylase activity are also described, as are pharmaceutical compositions thereof, methods of treatment by administration of the modulating compounds, and kits for practicing the method.

Abstract: A compound useful as a Sirt2 or Sirt5 inhibitor having the formula (1) wherein: R1 is a hydrocarbon group having at least two carbon atoms connected by carbon-carbon bonds, wherein said hydrocarbon group is optionally endcapped by a neutral or anionic oxygen-containing group; R2a, R2b, and R2c are independently selected from hydrogen atom and hydrocarbon groups; X0, X1, X2, and X3 are independently selected from —(CH2)n—, —NR5—, —O—, —S—, and a bond, wherein n represents 1, 2, or 3, provided that at least one of X0-X3 is —(CH2)n—; and R3 and R4 are independently selected from the group consisting of hydrogen atom, hydrocarbon groups, biological groups, and protecting groups. Also described are pharmaceutical compositions of the inhibiting compounds, and methods of treatment by administration of the inhibiting compounds.

Abstract: Method for identifying a modulator of Sirt6, PfSir2a, or Sirt7 deacylase activity, wherein a fatty-acylated substrate containing an acyl-lysine moiety and an indicator moiety is contacted with Sirt6, PfSir2a, or Sirt7 in the presence of a candidate compound under conditions for Sirt6, PfSir2a, or Sirt7 to deacylate the substrate, wherein the acyl is a hydrophobic fatty acyl group containing a hydrocarbon group having at least three carbon atoms connected by carbon-carbon bonds; contacting the deacylated substrate with a cleavage agent that cleaves the linkage between the lysine and indicator moiety to generate a detectable signal; and correlating a quantified Sirt6, PfSir2a, or Sirt7 deacylase activity therefrom. Modulating compounds of Sirt6, PfSir2a, or Sirt7 deacylase activity are also described, as are pharmaceutical compositions thereof, methods of treatment by administration of the modulating compounds, and kits for practicing the method.

Abstract: Sirt5, a mitochondrial Sirtuin, has been identified herein as an efficient demalonylase and desuccinylase. Disclosed herein are assays to identify Sirt5 modulators based on this robust enzymatic activity. Sirt5-specific modulators can be used study the biological function of Sirt5 and to target Sirt5 activities in treating human diseases.

Abstract: The instant application describes novel compounds that modulate (in particular, inhibit) Sirt2, with structures according to Formulas (1) and (2) provided herein. The invention is also directed to pharmaceutical compositions thereof, methods of treatment (i.e., cancer and neurodegenerative disease) by administration of the modulating compounds, assay methods for finding modulators of Sirt2, and kits for practicing the assay method.

Abstract: This disclosure demonstrates that inhibition of Sirt5 can suppress malignant transformation of cells. Therefore, methods of treating cancer based on inhibition of Sirt5 are disclosed.