Tag: M.W=350-400

Kim, Eunha published the artcileInhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro, Recommanded Product: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, the publication is European Journal of Pharmacology (2011), 672(1-3), 38-44, database is CAplus and MEDLINE.

Stearoyl-CoA desaturase1 (SCD1) whole body deficiency protects mice from diet-induced obesity. However the specific mechanism of how SCD1 deficiency protects mice from obesity is not clear yet. To understand the tissue-specific role of SCD1 in energy homeostasis, we investigated the responses of adipocytes, hepatocytes and myotubes to SCD1 inhibition. 3T3-L1 adipocytes treated with a SCD1 inhibitor had decreased expression of lipogenic genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol-regulatory element binding protein 1c (SREBP1c) while the expression of fatty acid oxidative genes including carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α) remained unaltered. In mouse primary hepatocytes, treatment with the inhibitor reduced the expression of FAS, ACC, and SREBP1c but increased the expression of fatty acid oxidative genes including acyl-CoA oxidase (AOX), CPT1, and PGC1-α. In addition, inhibitor-treated C2C12 myotubes showed decrease in ACC and FAS expression and increase in expression of CPT1, AOX and PGC1-α. AMP-activated protein kinase (AMPK) is known to regulate cellular metabolism in response to available energy and AMPK activation is associated with enhancement of fatty acid oxidation and suppression of lipogenesis. In all tested cell models, AMPK phosphorylation was increased significantly when SCD1 was inhibited. Taken together, our results indicate that inhibition of SCD1 activity has beneficial lipid metabolic effects of decreased lipogenesis and/or increased fatty acid oxidation, which is at least in part due to an increase of AMPK activation.

European Journal of Pharmacology published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C20H22ClN3O3, Recommanded Product: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Ma, Mark Kin Fai published the artcileStearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress-induced differentiation, Name: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, the publication is Journal of Hepatology (2017), 67(5), 979-990, database is CAplus and MEDLINE.

We investigated the functional role and clin. significance of stearoyl-CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulating liver tumor-initiating cells (T-ICs) and sorafenib resistance, with the aim of developing a novel therapeutic strategy against hepatocellular carcinomas (HCCs).We evaluated the clinic-pathol. relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clin. samples by qPCR and immunohistochem. analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize the functional roles of SCD1 in regulating liver T-ICs and sorafenib resistance. Mol. pathways mediating the phenotypic alterations were identified through RNA sequencing anal. and functional rescue experiments The combinatorial effect of SCD1 inhibition and sorafenib was tested using a patient-derived tumor xenograft (PDTX) model.SCD1 overexpression was found in HCC, which was associated with shorter disease-free survival (p = 0.008, log rank test). SCD1 was found to regulate the populations of liver T-ICs; while its suppression by a SCD1 inhibitor suppressed liver T-ICs and sorafenib resistance. Interestingly, SCD1 was markedly upregulated in our established sorafenib-resistant PDTX model, and its overexpression predicts the clin. response of HCC patients to sorafenib treatment. Suppression of SCD1 forces liver T-ICs to differentiate via ER stress-induced unfolded protein response, resulting in an enhanced sensitivity to sorafenib. The PDTX#1 model, combined with sorafenib treatment and a novel SCD1 inhibitor (SSI-4), showed a maximal growth suppressive effect.SCD1-mediated ER stress regulates liver T-ICs and sorafenib sensitivity. Targeting SCD1 alone or in combination with sorafenib might be a novel personalized medicine against HCC. In this study, SCD1 was found to play acrit. role in regulating liver tumor initiating cells and sorafenib resistance through the regulation of ER stress mediated differentiation. Targeting SCD1 in combination with sorafenib may be a novel therapeutic strategy against liver cancer.

Journal of Hepatology published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C20H22ClN3O3, Name: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Malesevic, Miroslav published the artcileAn improved method for the solution cyclization of peptides under pseudo-high dilution conditions, Application In Synthesis of 158922-07-7, the main research area is cyclopeptide solid phase synthesis; macrocyclization solid phase solution pseudo high dilution.

Depending on the ring size, the cyclization of peptides often is accompanied by dimerization or cyclodimerization. Hence, these macrocyclizations have to be performed under high dilution conditions. Efficient cyclization of peptides in solution with a min. amount of solvent succeeds, when a dual syringe pump is used to simultaneously add the linear peptide precursor and a coupling reagent from two sep. syringes.

Journal of Biotechnology published new progress about Dilution. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, Application In Synthesis of 158922-07-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zeng, Xiaojun published the artcileCopper-Catalyzed Decarboxylative Difluoromethylation, HPLC of Formula: 158922-07-7, the main research area is copper catalyzed decarboxylative difluoromethylation; difluoromethylation aliphatic carboxylic acid radical mechanism.

We report herein a highly efficient Cu-catalyzed protocol for the conversion of aliphatic carboxylic acids to the corresponding difluoromethylated analogs. This robust, operationally simple and scalable protocol tolerates a variety of functional groups and can convert a diverse array of acid-containing complex mols. to the alkyl-CF2H products. Mechanistic studies support the involvement of alkyl radicals.

Journal of the American Chemical Society published new progress about Alkylation. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, HPLC of Formula: 158922-07-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Nishizawa, Naoki published the artcileDesign and Synthesis of an Investigational Nonapeptide KISS1 Receptor (KISS1R) Agonist, Ac-D-Tyr-Hydroxyproline (Hyp)-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH2 (TAK-448), with Highly Potent Testosterone-Suppressive Activity and Excellent Water Solubility, SDS of cas: 158922-07-7, the main research area is nonapeptide KISS1 receptor agonist testosterone.

Metastin/kisspeptin is an endogenous ligand of KISS1R. Metastin and KISS1R are suggested to play crucial roles in regulating the secretion of GnRH and continuous administration of metastin derivatives attenuated the plasma testosterone levels in male rats. The optimization studies of metastin derivatives led to the discovery of Ac-D-Tyr-D-Trp-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH2, TAK-683, (I), which suppressed plasma testosterone in rats at lower doses than those of leuprolide. Although I possessed an extremely potent pharmacol. activity, 20-mg/mL aqueous solution of I has a gel formation property. In order to improve this physicochem. property, the authors substituted D-Trp at position 47 with a variety of amino acids; the authors identified that substitution with cyclic amino acids, which could change peptide conformation, retained its potency. Especially, Hyp47 analog TAK-448 (II) showed not only superior pharmacol. activity to I, but also excellent water solubility Furthermore, 20-mg/mL aqueous solution of 24 did not show a gel formation up to five days.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, SDS of cas: 158922-07-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Liu, Ruiwu published the artcileStructure-activity relationship studies of a series of peptidomimetic ligands for α4β1 integrin on Jurkat T-leukemia cells, Application In Synthesis of 158922-07-7, the main research area is peptide solid phase synthesis SAR integrin ligand anticancer.

α4β1 Integrin is a therapeutic target for inflammation, autoimmune diseases, and lymphoid cancers. A series of peptidomimetic ligands based on the Nle-D-I motif have been synthesized and their binding affinities (IC50) to activated α4β1 integrin on Jurkat T-leukemia cells were determined using a cell adhesion assay. One of the 51 ligands, peptide I, has an IC50 = 0.6 nM, more than two fold increase of binding affinity than the initial lead compound II. Extensive SAR studies provided important information for further ligand optimization, which has served as a foundation for studies that ultimately led to identification of a potent ligand with an IC50 = 2 pM.

Biopolymers published new progress about Antitumor agents. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, Application In Synthesis of 158922-07-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Vendrell, Marc published the artcileIndoloquinolizidine-peptide hybrids as multiple agonists for D1 and D2 dopamine receptors, Formula: C21H21NO4, the main research area is indoloquinolizidine peptide hybrid preparation dopamine receptor agonist structure activity; solid phase synthesis peptide combinatorial library indoloquinolizidine drug design; radioligand binding brain striatum membrane intracellular cAMP production assay; peptide indoloquinolizidine acid asym synthesis tryptophyl reduction hydrogenation hydrolysis.

Multiple-specificity ligands are considered promising pharmacol. tools that may show higher efficacy in the treatment of diseases for which the modulation of a single target is therapeutically inadequate. We prepared a set of novel ligands for D1 and D2 dopamine receptors by combining two indolo[2,3-a]quinolizidine scaffolds with various tripeptide moieties. The binding and functional properties of these mols. were determined by radioligand binding studies in brain striatum membranes and by intracellular cAMP production assays in cells expressing different dopamine receptor subtypes. Some indoloquinolizidine-peptide hybrids, mainly with the trans configuration, showed dual agonist activity at both D1 and D2 dopamine receptors and may therefore be useful for testing the therapeutic potential of multivalent drugs on these targets.

ChemMedChem published new progress about Animal cell line. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, Formula: C21H21NO4.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Arranz-Gibert, Pol published the artcileLipid Bilayer Crossing-The Gate of Symmetry. Water-Soluble Phenylproline-Based Blood-Brain Barrier Shuttles, Quality Control of 158922-07-7, the main research area is lipid bilayer permeation drug delivery phenylproline blood brain barrier.

Drug delivery to the brain can be achieved by various means, including blood-brain barrier (BBB) disruption, neurosurgical-based approaches, and mol. design. Recently, passive diffusion BBB shuttles have been developed to transport low-mol.-weight drug candidates to the brain which would not be able to cross unaided. The low water solubility of these BBB shuttles has, however, prevented them from becoming a mainstream tool to deliver cargos across membranes. Here, we describe the design, synthesis, physicochem. characterization, and BBB-transport properties of phenylproline tetrapeptides, (PhPro)4, an improved class of BBB shuttles that operates via passive diffusion. These PhPro-based BBB shuttles showed 3 orders of magnitude improvement in water solubility compared to the gold-standard (N-MePhe)4, while retaining very high transport values. Transport capacity was confirmed when two therapeutically relevant cargos, nipecotic acid and L-3,4-dihydroxyphenylalanine (i.e., L-DOPA), were attached to the shuttle. Addnl., we used the unique chiral and conformationally restricted character of the (PhPro)4 shuttle to probe its chiral interactions with the lipid bilayer of the BBB. We studied the transport properties of 16 (PhPro)4 stereoisomers using the parallel artificial membrane permeability assay and looked at differences in secondary structure. Most stereoisomers displayed excellent transport values, yet this study also revealed pairs of enantiomers with high enantiomeric discrimination and different secondary structure, where one enantiomer maintained its high transport values while the other had significantly lower values, thereby confirming that stereochem. plays a significant role in passive diffusion. This could open the door to the design of chiral and membrane-specific shuttles with potential applications in cell labeling and oncol.

Journal of the American Chemical Society published new progress about Biological permeation. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, Quality Control of 158922-07-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem