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Nonami, Atsushi,Sattler, Martin,Weisberg, Ellen,Liu, Qingsong,Zhang, Jianming,Patricelli, Matthew P.,Christie, Amanda L.,Saur, Amy M.,Kohl, Nancy E.,Kung, Andrew L.,Yoon, Hojong,Sim, Taebo,Gray, Natha American Society of Hematology 2015 Blood Vol.125 No.20
<P>Oncogenic forms of NRAS are frequently associated with hematologic malignancies and other cancers, making them important therapeutic targets. Inhibition of individual downstream effector molecules (eg, RAF kinase) have been complicated by the rapid development of resistance or activation of bypass pathways. For the purpose of identifying novel targets in NRAS-transformed cells, we performed a chemical screen using mutant NRAS transformed Ba/F3 cells to identify compounds with selective cytotoxicity. One of the compounds identified, GNF-7, potently and selectively inhibited NRAS-dependent cells in preclinical models of acute myelogenous leukemia and acute lymphoblastic leukemia. Mechanistic analysis revealed that its effects were mediated in part through combined inhibition of ACK1/AKT and of mitogen-activated protein kinase kinase kinase kinase 2 (germinal center kinase). Similar to genetic synthetic lethal approaches, these results suggest that small molecule screens can be used to identity novel therapeutic targets in cells addicted to RAS oncogenes.</P>
Griseusin C, a Novel Quinone Derivative from a Marine-Derived Fungus Penicillium sp.
Li, Xiang,Zheng, Yinan,Sattler, Isabel,Lin, Wenhan The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.11
A novel quinone derivative, Griseusin C (1), along with a known quinone, Naphthoquinone C (2), was isolated from the lyophilized culture broth of the marine-derived fungus Penicillium sp. The structures were elucidated on the basis of extensive 1D-and 2D-NMR, as well as HRESIMS, spectroscopic analysis. The relative stereochemistries of the compounds were assessed by NOESY analysis.
Cephalosporolides H and I, Two Novel Lactones from a Marine-Derived Fungus, Penicillium sp.
Yao, Yanhua,Zheng, Yinan,Sattler, Isabel,Lin, Wenhan,Li, Xiang 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.7
Two novel lactones, Cephalosporolides H (1) and I (2), were isolated from the lyophilized culture broth of the marine-derived fungus, Penicillium sp. The structures were elucidated on the basis of extensive 1D- and 2D-NMR, as well as HRESI-MS spectroscopic analyses. The relative stereochemistries of the compounds were assessed by comparison of the NOESY analysis and spectral data with those in the literature.
Metabolic Effects of Sulforaphane Oral Treatment in Streptozotocin-Diabetic Rats
Carolina Guerini de Souza,José Augusto Sattler,Adriano Martimbianco de Assis,Anderson Rech,Marcos Luiz Santos Perry 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.9
Diabetes has reached epidemic levels in the whole world, and the use of bioactive compounds that may have the capacity to prevent and treat diabetes is of great interest. Sulforaphane (SFN) is a compound which is found in cruciferous vegetables and that acts as both a potent antioxidant and regulator of gene expression. The aim of this study was to evaluate the effect of SFN in diabetes induced by streptozotocin (STZ). Male Wistar rats were gavaged with water or 0.1, 0.25, or 0.5 mg/kg of SFN before an injection of STZ (80 mg/kg). Animals treated with SFN showed fasting glycemia, insulin sensitivity, and hepatic glycogen concentrations, similar to the control group (nondiabetic), and different from the diabetic group. Diabetic animals also presented elevated levels of serum triacylglycerols (TAG), urea, and creatinine, and all SFN doses were able to reverse these alterations. However, the same doses of SFN accentuated alterations in total cholesterol, alanine, and aspartate aminotransferase levels, and had no effect on hepatic TAG, HDL cholesterol, and uptake of 2-deoxy glucose in adipose tissue and soleum muscle. Based on the effects inferred by the present data, SFN presented some positive effects against diabetes induction, although the impairment of hepatic function and cholesterol levels were aggravated after treatment with the compound.
Griseusin C, a Novel Quinone Derivative from a Marine-Derived Fungus Penicillium sp.
Xiang Li,Yinan Zheng,Isabel Sattler,Wenhan Lin 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.11
A novel quinone derivative, Griseusin C (1), along with a known quinone, Naphthoquinone C (2), was isolated from the lyophilized culture broth of the marine-derived fungus Penicillium sp. The structures were elucidated on the basis of extensive 1D- and 2D-NMR, as well as HRESIMS, spectroscopic analysis. The relative stereochemistries of the compounds were assessed by NOESY analysis.
Cephalosporolides H and I, Two Novel Lactones from a Marine-Derived Fungus, Penicillium sp.
Xiang Li,Yanhua Yao,Yinan Zheng,Isabel Sattler,Wenhan Lin 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.7
Two novel lactones, Cephalosporolides H (1) and I (2), were isolated from the lyophilized culture broth of the marine-derived fungus, Penicillium sp. The structures were elucidated on the basis of extensive 1D- and 2D-NMR, as well as HRESI-MS spectroscopic analyses. The relative stereochemistries of the compounds were assessed by comparison of the NOESY analysis and spectral data with those in the literature.
Characterization of anti-inflammatory effect of soybean septapeptide and its molecular mechanism
Kevin M. Lewis,Steven A. Sattler,ChulHee Kang,Hongmin Wu,Sang Geon Kim,김한복 한국미생물학회 2018 미생물학회지 Vol.54 No.3
Activation of nuclear factor kappa B (NFκB) leads to theinflammatory process. During this NFκB-dependent inflammationprocess, inducible nitric oxide synthase (iNOS) are expressedin the inflammatory cells. Our previous data indicated that aspecific septapeptide (GVAWWMY) from the soybean extractfermented by Bacillus licheniformis B1 inhibited iNOS mRNAexpression and NO production in cultured macrophage cells. Ourfurther experiments revealed that treatment of same septapeptideresulted in inhibition of LPS-induced NFκB activation byreversing degradation of IκBα, an inhibitory protein for NFκB. The molecular docking indicated that the septapeptide binds toIκB kinase β (IKKβ), and thus it can inhibit phosphorylation ofIκBα. Supporting this, the binding site for the septapeptide hasthe highest affinity (-8.7 kcal/mol) and the site was located atthe kinase domain (KD) of IKKβ, which can significantlyaffect the kinase activity of IKKβ.
Walker, Alexander M.,Hayes, Robert P.,Youn, Buhyun,Vermerris, Wilfred,Sattler, Scott E.,Kang, ChulHee American Society of Plant Biologists 2013 PLANT PHYSIOLOGY - Vol.162 No.2
<P><I>The catalytic mechanism and exact specificity for hydroxycinnamoyltransferase from sorghum were determined by comprehensive approaches with crystal structures of apo-form and ternary product complex, site-directed mutagenesis, and kinetic and thermodynamic analyses.</I></P>