Day: November 24, 2022

Targeting non-canonical pathways as a strategy to modulate the sodium iodide symporter was written by Read, Martin L.;Brookes, Katie;Thornton, Caitlin E. M.;Fletcher, Alice;Nieto, Hannah R.;Alshahrani, Mohammed;Khan, Rashida;Borges de Souza, Patricia;Zha, Ling;Webster, Jamie R. M.;Alderwick, Luke J.;Campbell, Moray J.;Boelaert, Kristien;Smith, Vicki E.;McCabe, Christopher J.. And the article was included in Cell Chemical Biology in 2022.Quality Control of 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid The following contents are mentioned in the article:

The sodium iodide symporter (NIS) functions to transport iodide and is critical for successful radioiodide ablation of cancer cells. Approaches to bolster NIS function and diminish recurrence post-radioiodide therapy are impeded by oncogenic pathways that suppress NIS, as well as the inherent complexity of NIS regulation. Here, we utilize NIS in high-throughput drug screening and undertake rigorous evaluation of lead compounds to identify and target key processes underpinning NIS function. We find that multiple proteostasis pathways, including proteasomal degradation and autophagy, are central to the cellular processing of NIS. Utilizing inhibitors targeting distinct mol. processes, we pinpoint combinatorial drug strategies giving robust >5-fold increases in radioiodide uptake. We also reveal significant dysregulation of core proteostasis genes in human tumors, identifying a 13-gene risk score classifier as an independent predictor of recurrence in radioiodide-treated patients. We thus propose and discuss a model for targetable steps of intracellular processing of NIS function. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0Quality Control of 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Quality Control of 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Probing the orientation of inhibitor and epoxy-eicosatrienoic acid binding in the active site of soluble epoxide hydrolase was written by Lee, Kin Sing Stephen;Henriksen, Niel M.;Ng, Connie J.;Yang, Jun;Jia, Weitao;Morisseau, Christophe;Andaya, Armann;Gilson, Michael K.;Hammock, Bruce D.. And the article was included in Archives of Biochemistry and Biophysics in 2017.Product Details of 1222780-33-7 The following contents are mentioned in the article:

Soluble epoxide hydrolase (sEH) is an important therapeutic target of many diseases, such as chronic obstructive pulmonary disease (COPD) and diabetic neuropathic pain. It acts by hydrolyzing and thus regulating specific bioactive long chain polyunsaturated fatty acid epoxides (lcPUFA), like epoxyeicosatrienoic acids (EETs). To better predict which epoxides could be hydrolyzed by sEH, one needs to dissect the important factors and structural requirements that govern the binding of the substrates to sEH. This knowledge allows further exploration of the physiol. role played by sEH. Unfortunately, a crystal structure of sEH with a substrate bound has not yet been reported. In this report, new photoaffinity mimics of a sEH inhibitor and EET regioisomers were prepared and used in combination with peptide sequencing and computational modeling, to identify the binding orientation of different regioisomers and enantiomers of EETs into the catalytic cavity of sEH. Results indicate that the stereochem. of the epoxide plays a crucial role in dictating the binding orientation of the substrate. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Product Details of 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Piperidine derivatives are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Product Details of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

A Supervised Molecular Dynamics Approach to Unbiased Ligand-Protein Unbinding was written by Deganutti, Giuseppe;Moro, Stefano;Reynolds, Christopher A.. And the article was included in Journal of Chemical Information and Modeling in 2020.Application of 1222780-33-7 The following contents are mentioned in the article:

The recent paradigm shift toward the use of the kinetics parameters in place of thermodn. constants is leading the computational chem. community to develop methods for studying the mechanisms of drug binding and unbinding. From this standpoint, mol. dynamics (MD) plays an important role in delivering insight at the mol. scale. However, a known limitation of MD is that the time scales are usually far from those involved in ligand-receptor unbinding events. Here, we show that the algorithm behind supervised MD (SuMD) can simulate the dissociation mechanism of druglike small mols. while avoiding the input of any energy bias to facilitate the transition. SuMD was tested on seven different intermol. complexes, covering four G protein-coupled receptors: the A_2A and A₁ adenosine receptors, the orexin 2 and the muscarinic 2 receptors, and the soluble globular enzyme epoxide hydrolase. SuMD well-described the multi-step nature of ligand-receptor dissociation, rationalized previous exptl. data and produced valuable working hypotheses for structure-kinetics relationships. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Application of 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.Application of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Three-Dimensional Quantitative Structure-Activity Relationship Analyses of 尾-Lactam Antibiotics and Tripeptides as Substrates of the Mammalian H⁺/Peptide Cotransporter PEPT1 was written by Biegel, Annegret;Gebauer, Sabine;Hartrodt, Bianka;Brandsch, Matthias;Neubert, Klaus;Thondorf, Iris. And the article was included in Journal of Medicinal Chemistry in 2005.Category: piperidines The following contents are mentioned in the article:

The utilization of the membrane transport protein PEPT1 as a drug delivery system is a promising strategy to enhance the oral bioavailability of drugs. Since very little is known about the substrate binding site of PEPT1, computational methods are a meaningful tool to gain a more detailed insight into the structural requirements for substrates. Three-dimensional quant. structure-activity relationship (3D-QSAR) studies using the comparative mol. similarity indexes anal. (Co-MSIA) method were performed on a training set of 98 compounds Affinity constants of 尾-lactam antibiotics and tripeptides were determined at Caco-2 cells. A statistically reliable model of high predictive power was obtained (q² = 0.828, r² = 0.937). The results derived from Co-MSIA were graphically interpreted using different field contribution maps. The authors identified those regions which are crucial for the interaction between peptidomimetics and PEPT1. The new 3D-QSAR model was used to design a new druglike compound mimicking a dipeptide. The predicted K_i value was confirmed exptl. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Category: piperidines).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Three-Dimensional Quantitative Structure-Activity Relationship Analyses of 尾-Lactam Antibiotics and Tripeptides as Substrates of the Mammalian H⁺/Peptide Cotransporter PEPT1 was written by Biegel, Annegret;Gebauer, Sabine;Hartrodt, Bianka;Brandsch, Matthias;Neubert, Klaus;Thondorf, Iris. And the article was included in Journal of Medicinal Chemistry in 2005.Related Products of 86069-86-5 The following contents are mentioned in the article:

The utilization of the membrane transport protein PEPT1 as a drug delivery system is a promising strategy to enhance the oral bioavailability of drugs. Since very little is known about the substrate binding site of PEPT1, computational methods are a meaningful tool to gain a more detailed insight into the structural requirements for substrates. Three-dimensional quant. structure-activity relationship (3D-QSAR) studies using the comparative mol. similarity indexes anal. (Co-MSIA) method were performed on a training set of 98 compounds Affinity constants of 尾-lactam antibiotics and tripeptides were determined at Caco-2 cells. A statistically reliable model of high predictive power was obtained (q² = 0.828, r² = 0.937). The results derived from Co-MSIA were graphically interpreted using different field contribution maps. The authors identified those regions which are crucial for the interaction between peptidomimetics and PEPT1. The new 3D-QSAR model was used to design a new druglike compound mimicking a dipeptide. The predicted K_i value was confirmed exptl. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Related Products of 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Related Products of 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Conformational Properties of Secondary Amino Acids: Replacement of Pipecolic Acid by N-Methyl-L-alanine in Efrapeptin C was written by Dutt Konar, Anita;Vass, Elemer;Hollosi, Miklos;Majer, Zsuzsanna;Grueber, Gerhard;Frese, Katrin;Sewald, Norbert. And the article was included in Chemistry & Biodiversity in 2013.Quality Control of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

The efrapeptins, a family of naturally occurring peptides with inhibitory activities against ATPases, contain several 伪,伪-disubstituted 伪-amino acids such as 伪-aminoisobutyric acid (Aib) or isovaline (Iva) besides pipecolic acid (Pip), 尾-Ala, Leu, Gly, and a C-terminal heterocyclic residue. Secondary 伪-amino acids such as proline are known to stabilize discrete conformations in peptides. A similar influence is ascribed to N-alkyl 伪-amino acids. We synthesized two efrapeptin C analogs with replacement of Pip by N-methyl-L-alanine (MeAla) using a combination of solid- and solution-phase techniques in a fragment-condensation strategy to compare the conformational bias of both secondary amino acids. The solution conformation was investigated by vibrational CD (VCD) to probe whether the analogs adopt a 3₁₀-helical conformation. The MeAla-containing analogs [MeAla^1,3]efrapeptin C and [MeAla^1,3,11]efrapeptin C inhibit ATP hydrolysis by the A₃B₃ complex of A₁A₀-ATP synthase from Methanosarcina mazei Goe1. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Quality Control of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Quality Control of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Conformational Properties of Secondary Amino Acids: Replacement of Pipecolic Acid by N-Methyl-L-alanine in Efrapeptin C was written by Dutt Konar, Anita;Vass, Elemer;Hollosi, Miklos;Majer, Zsuzsanna;Grueber, Gerhard;Frese, Katrin;Sewald, Norbert. And the article was included in Chemistry & Biodiversity in 2013.Safety of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

The efrapeptins, a family of naturally occurring peptides with inhibitory activities against ATPases, contain several 伪,伪-disubstituted 伪-amino acids such as 伪-aminoisobutyric acid (Aib) or isovaline (Iva) besides pipecolic acid (Pip), 尾-Ala, Leu, Gly, and a C-terminal heterocyclic residue. Secondary 伪-amino acids such as proline are known to stabilize discrete conformations in peptides. A similar influence is ascribed to N-alkyl 伪-amino acids. We synthesized two efrapeptin C analogs with replacement of Pip by N-methyl-L-alanine (MeAla) using a combination of solid- and solution-phase techniques in a fragment-condensation strategy to compare the conformational bias of both secondary amino acids. The solution conformation was investigated by vibrational CD (VCD) to probe whether the analogs adopt a 3₁₀-helical conformation. The MeAla-containing analogs [MeAla^1,3]efrapeptin C and [MeAla^1,3,11]efrapeptin C inhibit ATP hydrolysis by the A₃B₃ complex of A₁A₀-ATP synthase from Methanosarcina mazei Goe1. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Safety of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Safety of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Movement to the Clinic of Soluble Epoxide Hydrolase Inhibitor EC5026 as an Analgesic for Neuropathic Pain and for Use as a Nonaddictive Opioid Alternative was written by Hammock, Bruce D.;McReynolds, Cindy B.;Wagner, Karen;Buckpitt, Alan;Cortes-Puch, Irene;Croston, Glenn;Lee, Kin Sing Stephen;Yang, Jun;Schmidt, William K.;Hwang, Sung Hee. And the article was included in Journal of Medicinal Chemistry in 2021.Synthetic Route of C16H20F3N3O3 The following contents are mentioned in the article:

This report describes the development of an orally active analgesic that resolves inflammation and neuropathic pain without the addictive potential of opioids. EC5026 (I) acts on the cytochrome P 450 branch of the arachidonate cascade to stabilize epoxides of polyunsaturated fatty acids (EpFA), which are natural mediators that reduce pain, resolve inflammation, and maintain normal blood pressure. EC5026 is a slow-tight binding transition-state mimic that inhibits the soluble epoxide hydrolase (sEH) at picomolar concentrations The sEH rapidly degrades EpFA; thus, inhibiting sEH increases EpFA in vivo and confers beneficial effects. This mechanism addresses disease states by shifting endoplasmic reticulum stress from promoting cellular senescence and inflammation toward cell survival and homeostasis. We describe the synthesis and optimization of EC5026 and its development through human Phase 1a trials with no drug-related adverse events. Addnl., we outline fundamental work leading to discovery of the analgesic and inflammation-resolving CYP450 branch of the arachidonate cascade. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Synthetic Route of C16H20F3N3O3).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Synthetic Route of C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Oral treatment of rodents with soluble epoxide hydrolase inhibitor 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU): Resulting drug levels and modulation of oxylipin pattern was written by Ostermann, Annika I.;Herbers, Jan;Willenberg, Ina;Chen, Rongjun;Hwang, Sung Hee;Greite, Robert;Morisseau, Christophe;Gueler, Faikah;Hammock, Bruce D.;Schebb, Nils Helge. And the article was included in Prostaglandins and Other Lipid Mediators in 2015.Formula: C16H20F3N3O3 The following contents are mentioned in the article:

Epoxides from polyunsaturated fatty acids (PUFAs) are potent lipid mediators. In vivo stabilization of these epoxides by blockade of the soluble epoxide hydrolase (sEH) leads to anti-inflammatory, analgesic and normotensive effects. Therefore, sEH inhibitors (sEHi) are a promising new class of drugs. Herein, we characterized pharmacokinetic (PK) and pharmacodynamic properties of a com. available potent sEHi 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU). Cell culture studies suggest its high absorption and metabolic stability. Following administration in drinking water to rats (0.2, 1, and 5 mg TPPU/L with 0.2% PEG400), TPPU’s blood concentration increased dose dependently within the treatment period to reach an almost steady state after 8 days. TPPU was found in all the tissues tested. The linoleic epoxide/diol ratios in most tissues were dose dependently increased, indicating significant sEH inhibition. Overall, administration of TPPU with the drinking water led to systemic distribution as well as high drug levels and thus makes chronic sEH inhibition studies possible. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Formula: C16H20F3N3O3).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Piperidine derivatives bearing a masked aldehyde function in the 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Formula: C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

A HaloTag-Based Small Molecule Microarray Screening Methodology with Increased Sensitivity and Multiplex Capabilities was written by Noblin, Devin J.;Page, Charlotte M.;Tae, Hyun Seop;Gareiss, Peter C.;Schneekloth, John S.;Crews, Craig M.. And the article was included in ACS Chemical Biology in 2012.Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

Small Mol. Microarrays (SMMs) represent a general platform for screening small mol.-protein interactions independent of functional inhibition of target proteins. In an effort to increase the scope and utility of SMMs, the authors have modified the SMM screening methodol. to increase assay sensitivity and facilitate multiplex screening. Fusing target proteins to the HaloTag protein allows the authors to covalently prelabel fusion proteins with fluorophores, leading to increased assay sensitivity and an ability to conduct multiplex screens. The authors use the interaction between FKBP12 and two ligands, rapamycin and ARIAD’s bump ligand, to show that the HaloTag-based SMM screening methodol. significantly increases assay sensitivity. Addnl., using wild type FKBP12 and the FKBP12 F36V mutant, prelabeling various protein isoforms with different fluorophores allows the authors to conduct multiplex screens and identify ligands to a specific isoform. Finally, the authors show this multiplex screening technique is capable of identifying ligands selective for a specific PTP1B isoform using a 20,000-compound screening deck. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem