Month: November 2022

Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension was written by Wu, Patrick;Feng, QiPing;Kerchberger, Vern Eric;Nelson, Scott D.;Chen, Qingxia;Li, Bingshan;Edwards, Todd L.;Cox, Nancy J.;Phillips, Elizabeth J.;Stein, C. Michael;Roden, Dan M.;Denny, Joshua C.;Wei, Wei-Qi. And the article was included in Nature Communications in 2022.Application of 83799-24-0 The following contents are mentioned in the article:

Discovering novel uses for existing drugs, through drug repurposing, can reduce the time, costs, and risk of failure associated with new drug development. However, prioritizing drug repurposing candidates for downstream studies remains challenging. Here, we present a high-throughput approach to identify and validate drug repurposing candidates. This approach integrates human gene expression, drug perturbation, and clin. data from publicly available resources. We apply this approach to find drug repurposing candidates for two diseases, hyperlipidemia and hypertension. We screen >21,000 compounds and replicate ten approved drugs. We also identify 25 (seven for hyperlipidemia, eighteen for hypertension) drugs approved for other indications with therapeutic effects on clin. relevant biomarkers. For five of these drugs, the therapeutic effects are replicated in the All of Us Research Program database. We anticipate our approach will enable researchers to integrate multiple publicly available datasets to identify high priority drug repurposing opportunities for human diseases. 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: 83799-24-0Application of 83799-24-0).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) 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 are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Application of 83799-24-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

A Decade of Pharmacogenetic Studies in Jordan: A Systemic Review was written by Yehya, Alaa;Altaany, Zaid. And the article was included in Pharmacogenomics Journal in 2021.SDS of cas: 83799-24-0 The following contents are mentioned in the article:

The aim of this study was to perform a systematic overview of the pharmacogenetic studies conducted in Jordan. A structured search of Medline was conducted for articles over the last decade (Jan. 2010-July 2020). Studies were classified by design, sample size, drug-gene combination, and the significance of the results. Thirty-two studies met the criteria for review. Most pharmacogenomic studies had a case-only design (n = 23). Only five studies included >500 participants. The total number of genetic variants in all studies was one hundred fifteen, which were found in forty genes, including dynamic (n = 27), and kinetic (n = 9) genes. The most commonly studied drugs were within the hematol. and cardiol. therapeutic areas and included statins, warfarin, aspirin, and clopidogrel. Most studies (n = 18) reported results with mixed p values [<0.05 and >0.05]. Pharmacogenomic research in Jordan is still in its infancy and is limited mainly to replication attempts. The need for standardization is imperative, especially in developing countries with scarce funding resources. 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: 83799-24-0SDS of cas: 83799-24-0).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) 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 bearing a masked aldehyde function in the 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.SDS of cas: 83799-24-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of Potent Antagonists of the Antiapoptotic Protein XIAP for the Treatment of Cancer was written by Oost, Thorsten K.;Sun, Chaohong;Armstrong, Robert C.;Al-Assaad, Ali-Samer;Betz, Stephen F.;Deckwerth, Thomas L.;Ding, Hong;Elmore, Steven W.;Meadows, Robert P.;Olejniczak, Edward T.;Oleksijew, Andrew;Oltersdorf, Tilman;Rosenberg, Saul H.;Shoemaker, Alexander R.;Tomaselli, Kevin J.;Zou, Hua;Fesik, Stephen W.. And the article was included in Journal of Medicinal Chemistry in 2004.Reference of 86069-86-5 The following contents are mentioned in the article:

Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogs that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small mol. XIAP antagonists as a potential therapy for cancers that overexpress XIAP. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Reference 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 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.Reference of 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of Potent Antagonists of the Antiapoptotic Protein XIAP for the Treatment of Cancer was written by Oost, Thorsten K.;Sun, Chaohong;Armstrong, Robert C.;Al-Assaad, Ali-Samer;Betz, Stephen F.;Deckwerth, Thomas L.;Ding, Hong;Elmore, Steven W.;Meadows, Robert P.;Olejniczak, Edward T.;Oleksijew, Andrew;Oltersdorf, Tilman;Rosenberg, Saul H.;Shoemaker, Alexander R.;Tomaselli, Kevin J.;Zou, Hua;Fesik, Stephen W.. And the article was included in Journal of Medicinal Chemistry in 2004.Recommanded Product: 86069-86-5 The following contents are mentioned in the article:

Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogs that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small mol. XIAP antagonists as a potential therapy for cancers that overexpress XIAP. 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: 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. 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: 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption was written by Napimoga, M. H.;Rocha, E. P.;Trindade-da-Silva, C. A.;Demasi, A. P. D.;Martinez, E. F.;Macedo, C. G.;Abdalla, H. B.;Bettaieb, A.;Haj, F. G.;Clemente-Napimoga, J. T.;Inceoglu, B.;Hammock, B. D.. And the article was included in Journal of Periodontal Research in 2018.Category: piperidines The following contents are mentioned in the article:

In the current study we used the sEH inhibitor (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea [TPPU]) to investigate the immunomodulatory effects in a mouse periodontitis model. Mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 6) that were treated orally, daily for 15 days, with 1 mg/kg of TPPU. Then, the mice were killed and their jaws were analyzed for bone resorption using morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by microarray PCR or western blotting. Infected mice treated with TPPU showed lower bone resorption than infected mice without treatment. Interestingly, infected mice showed increased expression of sEH; however, mice treated with TPPU had a reduction in expression of sEH. Besides, several proinflammatory cytokines and mol. markers were downregulated in the gingival tissue in the group treated with 1 mg/kg of TPPU. The sEH inhibitor, TPPU, showed immunomodulatory effects, decreasing bone resorption and inflammatory responses in a bone resorption mouse model. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Category: piperidines).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. 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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

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