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Corynoxine B


Catalogue Number : BD-D0323
Specification : HPLC≥98%
CAS number : 17391-18-3
Formula : C22H28N2O4
Molecular Weight : 384.48
PUBCHEM ID : 10091424
Volume : 10mg

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Catalogue Number


Analysis Method






Molecular Weight



White powder

Botanical Source

Uncaria rhynchophylla(Miq.)Miq. ex Havil.

Structure Type



Standards;Natural Pytochemical;API




Spiro[3H-indole-3,1'(5'H)-indolizine]-7'-acetic acid, 6'-ethyl-1,2,2',3',6',7',8',8'a-octahydro-α-(methoxymethylene)-2-oxo-, methyl ester, (αE,3R,6'S,7'S,8'aS)-/Corynoxine B/Methyl (7β,16E)-16-(methoxymethylene)-2-oxocorynoxan-17-oate


methyl (E)-2-[(3R,6'S,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate


1.2±0.1 g/cm3


Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.

Flash Point

293.0±30.1 °C

Boiling Point

560.8±50.0 °C at 760 mmHg

Melting Point



InChl Key


WGK Germany


HS Code Reference


Personal Projective Equipment

Correct Usage

For Reference Standard and R&D, Not for Human Use Directly.

Meta Tag

provides coniferyl ferulate(CAS#:17391-18-3) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate

No Technical Documents Available For This Product.




Citrate is a key regulatory metabolic intermediate as it facilitates the integration of the glycolysis and lipid synthesis pathways. Inhibition of hepatic extracellular citrate uptake, by blocking the sodium-coupled citrate transporter (NaCT or SLC13A5), has been suggested as a potential therapeutic approach to treat metabolic disorders. NaCT transports citrate from the blood into the cell coupled to the transport of sodium ions. The studies herein report the identification and characterization of a novel small dicarboxylate molecule (compound 2) capable of selectively and potently inhibiting citrate transport through NaCT, both in vitro and in vivo. Binding and transport experiments indicate that 2 specifically binds NaCT in a competitive and stereosensitive manner, and is recognized as a substrate for transport by NaCT. The favorable pharmacokinetic properties of 2 permitted in vivo experiments to evaluate the effect of inhibiting hepatic citrate uptake on metabolic endpoints.

Fatty liver is a frequent co-morbidity of type 2 diabetes (T2D) and obesity. Therapies that could simultaneously target both pathogenic elevations in liver fat, and hyperglycemia, are highly desirable because in T2D, the elevations in circulating plasma glucose concentrations can be partially attributed to increased hepatic glucose production due to elevations in hepatic gluconeogenesis1,2,3. Additionally, increased liver fat associated with non-alcoholic fatty liver disease (NAFLD) is considered a pre-requisite for the development of non-alcoholic steatohepatitis (NASH)4. Thiazolidinediones (TZDs) used as anti-diabetes therapies exert multiple benefits on hepatic metabolism by reducing both liver fat and hepatic gluconeogenesis5,6. However, the side effects associated with TZDs such as weight gain and bone fractures have drastically reduced the use of this class of drugs7. More recently, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-IV) inhibitors have become well established diabetes treatments with demonstrated benefits on reducing hepatic fat as well8. Alternative mechanisms capable of decreasing both hepatic lipid burden and glucose production remain of significant interest for the treatment of T2D.

Citrate is a key metabolite involved in intracellular signaling. Through allosteric modulation, citrate inhibits phosphofructokinase (PFK), thereby reducing glycolytic flux9. Citrate also promotes the polymerization and thus activation of acetyl-CoA carboxylase (ACC)10, which catalyzes the rate limiting step in de novo lipogenesis (DNL). Blocking the cellular uptake of citrate is hypothesized to have beneficial metabolic effects by reducing the energy burden placed on cells11. NaDC1, NaDC3, and NaCT (encoded by SLC13A2, SLC13A3, and SLC13A5, respectively) are critical carrier proteins that co-transport sodium ions with Krebs cycle intermediates such as citrate and succinate from the extracellular space into the cell12. In humans, NaDC1 and NaDC3 are di- and tri-carboxylate transporters primarily expressed in the intestine and kidney. While these transporters bind citrate with a lower affinity than other Krebs cycle intermediates, NaDC1 and NaDC3 play an important role in the absorption and excretion of citrate13. SLC13A5 expression is enriched in the human liver and appears to be the predominant plasma membrane citrate transporter expressed13. NaCT, on the other hand, is the only known plasma membrane carrier to preferentially transport citrate over dicarboxylates14. The expression profile and reported substrate selectivity of NaCT make it an attractive target to alter hepatic citrate uptake15.

The regulation of metabolic processes by SLC13A5 was revealed through studies with its homolog in Drosophila melanogaster and Caenorhabditis elegans16,17,18. In these species, inactivation of SLC13a5 specifically resulted in lifespan extension, analogous to the results observed with caloric restriction. In a mammalian model, SLC13a5 knockout (KO) mice show improvements in glycemic control as demonstrated by increases in the glucose infusion rate required to maintain euglycemia in a hyperinsulinemic-euglycemic clamp, which can be attributed to suppression of glucose production19. Additionally, SLC13a5 KO mice that have been fed a high fat diet (HFD) display reductions in body weight and hepatic lipid concentrations including diacylglycerides (DAG) and triglycerides (TAG) relative to their wild type (WT) counterparts. Studies using antisense oligonucleotides (ASO) to knock down SLC13a5 in rats on a HFD corroborated the KO data, demonstrating improvements in insulin responsiveness which was attributed to improvements in hepatic glucose production and insulin responsiveness20. Taken together, these data suggest that pharmacological inhibition of NaCT may prove to be a beneficial strategy for treating metabolic disorders.

Sun et al. (2010) reported small molecule inhibitors of NaCT that were identified via virtual docking using a homology model of NaCT, and a proteoliposome-based assay was used to measure their weak inhibitory activity on citrate transport (<73% inhibition at 1 mM)21. NaDC1 and NaDC3 inhibitors reported by Pajor and Randolph (2007) also displayed weak inhibition of NaCT in transfected CUBS cells22. However, in our hands these compounds exhibited cytotoxicity in HEK-293-derived cell-based assays (using a CellTiter-glo® assessment) thereby confounding the interpretation of citrate uptake activity (Figure S1). Moreover, all previously reported NaCT inhibitors displayed poor ADME properties precluding their use in in vivo experiments. More recently, Colas and collaborators described the identification of new NaDC1 and NaDC3 inhibitors via virtual docking in homology models, with one example also displaying weak inhibitory activity against NaCT (~30% inhibition at 500 μM)23. Herein, the identification of the first potent and selective small molecule probe for NaCT which inhibits cellular citrate uptake in vitro and hepatic citrate uptake in vivo is described. Inhibition of NaCT resulted in lower hepatic lipid concentrations and improved glycemic control in mice fed a HFD, which supports the further exploration of NaCT inhibitors for the treatment of metabolic diseases.


Discovery and characterization of novel inhibitors of the sodium-coupled citrate transporter (NaCT or SLC13A5)


Kim Huard,a,1 Janice Brown,2 Jessica C. Jones,3 Shawn Cabral,4 Kentaro Futatsugi,1 Matthew Gorgoglione,3 Adhiraj Lanba,3 Nicholas B. Vera,3 Yimin Zhu,3 Qingyun Yan,3 Yingjiang Zhou,3 Cecile Vernochet,3 Keith Riccardi,2 Angela Wolford,2 David Pirman,2 Mark Niosi,2 Gary Aspnes,1 Michael Herr,4 Nathan E. Genung,4 Thomas V. Magee,1 Daniel P. Uccello,4 Paula Loria,2 Li Di,2 James R. Gosset,5 David Hepworth,1 Timothy Rolph,3 Jeffrey A. Pfefferkorn,3 and Derek M. Erionb,3

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We recently found that induction of the anti-inflammatory SOCS-3 gene by cyclic AMP occurs through novel cyclic AMP-dependent protein kinase-independent mechanisms involving activation of CCAAT/enhancer-binding protein (C/EBP) transcription factors, notably C/EBPβ, by the cyclic AMP GEF EPAC1 and the Rap1 GTPase. In this study we show that down-regulation of phospholipase (PL) Cϵ with small interfering RNA or blockade of PLC activity with chemical inhibitors ablates exchange protein directly activated by cyclic AMP (EPAC)-dependent induction of SOCS-3 in COS1 cells. Consistent with this, stimulation of cells with 1-oleoyl-2-acetyl-sn-glycerol and phorbol 12-myristate 13-acetate, both cell-permeable analogues of the PLC product diacylglycerol, are sufficient to induce SOCS-3 expression in a Ca2+-dependent manner. Moreover, the diacylglycerol- and Ca2+-dependent protein kinase C (PKC) isoform PKCα becomes activated following cyclic AMP elevation or EPAC stimulation. Conversely, down-regulation of PKC activity with chemical inhibitors or small interfering RNA-mediated depletion of PKCα or -δ blocks EPAC-dependent SOCS-3 induction. Using the MEK inhibitor U0126, we found that activation of ERK MAPKs is essential for SOCS-3 induction by either cyclic AMP or PKC. C/EBPβ is known to be phosphorylated and activated by ERK. Accordingly, we found ERK activation to be essential for cyclic AMP-dependent C/EBP activation and C/EBPβ-dependent SOCS-3 induction by cyclic AMP and PKC. Moreover, overexpression of a mutant form of C/EBPβ (T235A), which lacks the ERK phosphorylation site, blocks SOCS-3 induction by cyclic AMP and PKC in a dominant-negative manner. Together, these results indicate that EPAC mediates novel regulatory cross-talk between the cyclic AMP and PKC signaling pathways leading to ERK- and C/EBPβ-dependent induction of the SOCS-3 gene.


Activation of Protein Kinase Cα by EPAC1 Is Required for the ERK- and CCAAT/Enhancer-binding Protein β-dependent Induction of the SOCS-3 Gene by Cyclic AMP in COS1 Cells*An external file that holds a picture, illustration, etc. Object name is sbox.jpg


Gillian Borland,1 Rebecca J. Bird,1,2 Timothy M. Palmer, and Stephen J. Yarwood3

Publish date

2009 Jun 26;




Cardiovascular diseases form the most common cause of death worldwide, with atherosclerosis as main etiology. Atherosclerosis is marked by cholesterol rich lipoprotein deposition in the artery wall, evoking a pathogenic immune response. Characteristic for the disease is the pathogenic accumulation of macrophages in the atherosclerotic lesion, which become foam cells after ingestion of large quantities of lipoproteins. We hypothesized that, by inducing a CD8 T cell response towards lipoprotein derived apolipoprotein-B100 (ApoB100), lesional macrophages, that are likely to cross-present lipoprotein constituents, can specifically be eliminated. Based on in silico models for protein processing and MHC-I binding, 6 putative CD8 T cell epitopes derived from ApoB100 were synthesized. HLA-A2 binding was confirmed for all peptides by T2 cell binding assays and recall responses after vaccination with the peptides proved that 5 of 6 peptides could induce CD8 T cell responses. Induction of ApoB100 specific CD8 T cells did not impact plaque size and cellular composition in HLA-A2 and human ApoB100 transgenic LDLr−/− mice. No recall response could be detected in cultures of cells isolated from the aortic arch, which were observed in cell cultures of splenocytes and mesenteric lymph nodes, suggesting that the atherosclerotic environment impairs CD8 T cell activation.

Subject terms: Lymphocyte activation, Peptide vaccines, Cardiovascular diseases


Induction of HLA-A2 restricted CD8 T cell responses against ApoB100 peptides does not affect atherosclerosis in a humanized mouse model


Frank H. Schaftenaar,corresponding author1 Jacob Amersfoort,1 Hidde Douna,1 Mara J. Kroner,1 Amanda C. Foks,1 Ilze Bot,1 Bram A. Slutter,1 Gijs H. M. van Puijvelde,1 Jan W. Drijfhout,2 and Johan Kuipercorresponding author1

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