Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression

Pirat, Céline; Dacquet, Catherine; Leclerc, Véronique; Hennuyer, Nathalie; Beucher-Gaudin, Monique; Zanirato, Ghislaine; Géant, Anne; Staels, Bart; Ktorza, Alain; Farce, Amaury; Caignard, Daniel‐Henri; Berthelot, Pascal; Lebegue, Nicolas

doi:10.1016/j.ejmech.2017.06.006

Cited by 7 publications

(4 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ion channels (e.g., ENaC and KCNE1/KCNQ1), carriers (such as NCC and NHE3), Na(+)/K(+)-ATPase, enzymes (including GSK3), and transcription factors or regulators (including forkhead box O 3a (FOXO3a), NF-kappaB, b-catenin and p27) are extensively regulated by SGK1 (6). Thus, SGK1 impacts a wide variety of physiological functions (7) and plays an active role in the pathophysiology of several disorders, including hypertension (8), diabetes (9), inflammation (10), autoimmune disease (11), and tumor growth (12). SGK1 belongs to the "AGC" subfamily of protein kinases, containing 60 members, including PKA, PKG, and PKC, which all share a conserved catalytic kinase domain (13).…”

Section: Introductionmentioning

confidence: 99%

SGK1 in Human Cancer: Emerging Roles and Mechanisms

et al. 2021

View full text Add to dashboard Cite

Serum and glucocorticoid-induced protein kinase 1 (SGK1) is a member of the “AGC” subfamily of protein kinases, which shares structural and functional similarities with the AKT family of kinases and displays serine/threonine kinase activity. Aberrant expression of SGK1 has profound cellular consequences and is closely correlated with human cancer. SGK1 is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in the genesis and development of many human cancers. Abnormal expression of SGK1 has been found in tissue and may hopefully become a useful indicator of cancer progression. In addition, SGK1 acts as a prognostic factor for cancer patient survival. This review systematically summarizes and discusses the role of SGK1 as a diagnostic and prognostic biomarker of diverse cancer types; focuses on its essential roles and functions in tumorigenesis, cancer cell proliferation, apoptosis, invasion, metastasis, autophagy, metabolism, and therapy resistance and in the tumor microenvironment; and finally summarizes the current understanding of the regulatory mechanisms of SGK1 at the molecular level. Taken together, this evidence highlights the crucial role of SGK1 in tumorigenesis and cancer progression, revealing why it has emerged as a potential target for cancer therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

SGK1 in Human Cancer: Emerging Roles and Mechanisms

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Functionalization of the ketone tail portion of the acyl group with O-methyl oxime ether or introduction of a trifluoroethoxy group in previous PPAR agonist series developed in our laboratory were found to respectively enhance PPARa and decrease PPARc functional activity 15,33,36 . These chemical modulations were then applied by oxime forming reactions on the benzoyl part of ethoxy 32a or trifluoroethoxy 32 b racemates in order to assess the impact of the nature of the substituents on PPAR transactivation ( Table 2).…”

Section: In Vitro Evaluation: Binding Studies and Transactivation Assaysmentioning

confidence: 96%

“…MS (ESI þ ) m/z 538.3 [M þ H] þ .2.1.36. General procedure for synthesis of carboxylic acids(31)(32)(33)(34)(35)(36)(37)(38) A solution of ester 23-30 (0.5 mmol, 1.0 eq) and lithium hydroxide (36 mg, 1.5 mmol, 3.0 eq) in THF/H 2 O (3:2, 15 mL) is stirred at room temperature for 10 h. After removal of the solvent in vacuo, 1 N HCl aqueous solution (10 mL) is added and the resulting precipitate is filtered and purified by flash column chromatography (DCM/MeOH 9:1) to yield the corresponding carboxylic acid. for C 28 H 25 F 2 NO 6 : C, 66.01; H, 4.95; N, 2.75; found C, 66.22; H, 5.01; N, 2.69.…”

mentioning

confidence: 99%

Effect of 6-Benzoyl-benzothiazol-2-one scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists

Hurtevent

Naour

Leclerc

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

“…Derivative 26 was prepared [30] quantitatively from ethyl 2-(diethoxyphosphoryl)acetate (25) utilizing p-toluenesulfonyl azide as a diazo transfer reagent. Thereafter, a catalytic amount of rhodium(II) acetate dimer was used to generate a carbenoid from the diazo compound 26, which was inserted into the OÀ H bond of 1,3-propanediol to provide 27 in a 60 % yield.…”

Section: Chemistrymentioning

confidence: 99%

N2′‐Branched Acyclic Nucleoside Phosphonates Containing 9‐Deazahypoxanthine as Inhibitors of Plasmodium falciparum 6‐Oxopurine Phosphoribosyltransferase

et al. 2023

View full text Add to dashboard Cite

Twelve N2′‐branched acyclic nucleoside phosphonates and bisphosphonates were synthesized as potential inhibitors of Plasmodium falciparum hypoxanthine‐guanine‐xanthine phosphoribosyltransferase (PfHGXPRT), the key enzyme in the purine salvage pathway for production of purine nucleotides. The chemical structures were designed with the aim to study selectivity of the inhibitors for PfHGXPRT over human HGPRT. The newly prepared compounds contain 9‐deazahypoxanthine connected to a phosphonate group via a five‐atom‐linker bearing a nitrogen atom (N2′) as a branching point. All compounds, with the additional phosphonate group(s) in the second aliphatic linker attached to N2′ atom, were low micromolar inhibitors of PfHGXPRT with low to modest selectivity for the parasite enzyme over human HGPRT. The effect of the addition of different chemical groups/linkers to N2′ atom on the inhibition constants and selectivity is discussed.

show abstract

Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression

Cited by 7 publications

References 73 publications

SGK1 in Human Cancer: Emerging Roles and Mechanisms

SGK1 in Human Cancer: Emerging Roles and Mechanisms

Effect of 6-Benzoyl-benzothiazol-2-one scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists

N2′‐Branched Acyclic Nucleoside Phosphonates Containing 9‐Deazahypoxanthine as Inhibitors of Plasmodium falciparum 6‐Oxopurine Phosphoribosyltransferase

Contact Info

Product

Resources

About