Novel compounds reducing IRS-1 serine phosphorylation for treatment of diabetes

Simon-Szabó, Laura; Kokas, Márton; Greff, Zoltán; Boros, Sándor; Bánhegyi, Péter; Zsákai, Lilian; Szántai-Kis, Csaba; Vántus, Tibor; Mandl, József; Bánhegyi, Gábor; Vályi‐Nagy, István; Őrfi, László; Ullrich, Axel; Csala, Miklós; Kéri, Gÿorgý

doi:10.1016/j.bmcl.2015.11.099

Cited by 10 publications

(5 citation statements)

References 20 publications

(17 reference statements)

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“…Investigation of lipotoxicity in RINm5F cells has been established in our laboratory [8,16,20]. Cell viability was assessed by using an MTT assay after 24 h treatments with palmitate or co-treatments with palmitate and an unsaturated FA at 250 or 500 µM individual concentrations.…”

Section: Effect Of Unsaturated Fatty Acids On Palmitate-induced Cell mentioning

confidence: 99%

Effect of cis- and trans-Monounsaturated Fatty Acids on Palmitate Toxicity and on Palmitate-induced Accumulation of Ceramides and Diglycerides

Sarnyai

Somogyi

Gór-Nagy

et al. 2020

IJMS

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Dietary trans fatty acids (TFAs) have been implicated in serious health risks, yet little is known about their cellular effects and metabolism. We aim to undertake an in vitro comparison of two representative TFAs (elaidate and vaccenate) to the best-characterized endogenous cis-unsaturated FA (oleate). The present study addresses the possible protective action of TFAs on palmitate-treated RINm5F insulinoma cells with special regards to apoptosis, endoplasmic reticulum stress and the underlying ceramide and diglyceride (DG) accumulation. Both TFAs significantly improved cell viability and reduced apoptosis in palmitate-treated cells. They mildly attenuated palmitate-induced XBP-1 mRNA cleavage and phosphorylation of eukaryotic initiation factor 2α (eIF2α) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), but they were markedly less potent than oleate. Accordingly, all the three unsaturated FAs markedly reduced cellular palmitate incorporation and prevented harmful ceramide and DG accumulation. However, more elaidate or vaccenate than oleate was inserted into ceramides and DGs. Our results revealed a protective effect of TFAs in short-term palmitate toxicity, yet they also provide important in vitro evidence and even a potential mechanism for unfavorable long-term health effects of TFAs compared to oleate.

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Section: Effect Of Unsaturated Fatty Acids On Palmitate-induced Cell mentioning

confidence: 99%

Effect of cis- and trans-Monounsaturated Fatty Acids on Palmitate Toxicity and on Palmitate-induced Accumulation of Ceramides and Diglycerides

Sarnyai

Somogyi

Gór-Nagy

et al. 2020

IJMS

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“…On the contrary, in the case of the structures 10 (C5-C6 double bond), 53.53% present only a substituent at C6 (R 5 = H) with the following distribution referring to the total number of structures: 44.46% carbon substituent [55,56] (32.12% phenyl ring [42,57,58]), 4.70% oxygen substituent [59,60], and 1.00% nitrogen substituent [32,61]. In 7.05% of the structures there is a substituent at C5 (R 6 = H) with the following distribution referring to the total number of structures: 4.16% carbon substituent [62,63] (0.10% phenyl ring [16,56]), 0.47% oxygen substituent [56,64], and 2.39% nitrogen substituent [64,65].…”

Section: Substitution Pattern At C5 and C6mentioning

confidence: 99%

Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications

et al. 2019

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Pyrido[2,3-d]pyrimidines (1) are a type of privileged heterocyclic scaffolds capable of providing ligands for several receptors in the body. Among such structures, our group and others have been particularly interested in pyrido[2,3-d]pyrimidine-7(8H)-ones (2) due to the similitude with nitrogen bases present in DNA and RNA. Currently there are more than 20,000 structures 2 described which correspond to around 2900 references (half of them being patents). Furthermore, the number of references containing compounds of general structure 2 have increased almost exponentially in the last 10 years. The present review covers the synthetic methods used for the synthesis of pyrido[2,3-d]pyrimidine-7(8H)-ones (2), both starting from a preformed pyrimidine ring or a pyridine ring, and the biomedical applications of such compounds.

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“…The inhibition activity of pyrido [2,3-d]pyrimidine derivatives toward CK2 kinase has not been studied. Noteworthy, the substituted pyrido [2,3-d]pyrimidines are the inhibitors of EGFR [21][22][23][24], Cyclin-Dependent kinases [25,26], Src-tyrosine kinase [27,28] and c-Jun N-Terminal kinase (JNK) [29,30]. It was found that among 2-substituted pyrido [2,3-d]pyrimidin-7-one derivatives there are powerful selective inhibitors of CDK4/6 kinase (Palbociclib) [25], Abl kinase (PD173955) [31,32] and p38 MAP kinase (Pamapimod) [33] which are effective in the treatment of autoimmune and cancer diseases.…”

Section: Bioorganic Chemistrymentioning

confidence: 99%

Synthesis and biological evaluation of novel amino-substituted derivatives of pyrido[2,3-d]pyrimidine as inhibitors of protein kinase CK2

et al. 2017

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A search for human protein kinase CK2 inhibitors in a series of new amino-substituted pyrido[2,3-d]pyrimidine derivatives. Methods. Organic synthesis, analytical and spectral methods, molecular docking, in vitro biochemical testing. Results. Synthesis of new pyrido[2,3d]pyrimidine derivatives with various aminogroups in position[s] 4 and 6 of the heterocycle was developed. Two compounds inhibiting kinase CK2 in micromolar concentrations were found among these derivatives. Conclusion. New pyrido[2,3-d]pyrimidin-7-ones containing aminogroups in position[s] 4 and 6 of heterocyclic system and new 4-amino-substituted pyrido[2,3-d]pyrimidin-7-amine derivatives have been synthesized. The inhibition activity of new pyrido[2,3-d]pyrimidines has been examined and the optimization modes have been suggested. Methyl-2-[(7-aminopyrido[2,3-d]pyrimidine-6-yl)amino]benzoate and N-(4-anilino-7oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-yl)-3,4-dimethoxy-benzamide were found to inhibit protein kinase CK2 at IC50 of 6 and 19.5 μМ, respectively.

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Novel compounds reducing IRS-1 serine phosphorylation for treatment of diabetes

Abstract: Leave this area blank for abstract info.

Cited by 10 publications

References 20 publications

Effect of cis- and trans-Monounsaturated Fatty Acids on Palmitate Toxicity and on Palmitate-induced Accumulation of Ceramides and Diglycerides

Effect of cis- and trans-Monounsaturated Fatty Acids on Palmitate Toxicity and on Palmitate-induced Accumulation of Ceramides and Diglycerides

Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications

Synthesis and biological evaluation of novel amino-substituted derivatives of pyrido[2,3-d]pyrimidine as inhibitors of protein kinase CK2

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