Day: November 24, 2022

Uncertainty Quantification in Alchemical Free Energy Methods was written by Bhati, Agastya P.;Wan, Shunzhou;Hu, Yuan;Sherborne, Brad;Coveney, Peter V.. And the article was included in Journal of Chemical Theory and Computation in 2018.Recommanded Product: 219580-11-7 The following contents are mentioned in the article:

Alchem. free energy methods have gained much importance recently from several reports of improved ligand-protein binding affinity predictions based on their implementation using mol. dynamics simulations. A large number of variants of such methods implementing different accelerated sampling techniques and free energy estimators are available, each claimed to be better than the others in its own way. However, the key features of reproducibility and quantification of associated uncertainties in such methods have barely been discussed. Here, we apply a systematic protocol for uncertainty quantification to a number of popular alchem. free energy methods, covering both absolute and relative free energy predictions. We show that a reliable measure of error estimation is provided by ensemble simulation-an ensemble of independent MD simulations-which applies irresp. of the free energy method. The need to use ensemble methods is fundamental and holds regardless of the duration of time of the mol. dynamics simulations performed. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Recommanded Product: 219580-11-7).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Recommanded Product: 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Activation-Induced Cytidine Deaminase Regulates Fibroblast Growth Factor/Extracellular Signal-Regulated Kinases Signaling to Achieve the Naive Pluripotent State During Reprogramming was written by Kumar, Ritu;Evans, Todd. And the article was included in Stem Cells (Durham, NC, United States) in 2019.Related Products of 219580-11-7 The following contents are mentioned in the article:

Induced pluripotent stem cells (iPSCs) derived by in vitro reprogramming of somatic cells retain the capacity to self-renew and to differentiate into many cell types. Pluripotency encompasses multiple states, with naive iPSCs considered as ground state, possessing high levels of self-renewal capacity and maximum potential without lineage restriction. We showed previously that activation-induced cytidine deaminase (AICDA) facilitates stabilization of pluripotency during reprogramming. Here, we report that Acida^-/- iPSCs, even when successfully reprogrammed, fail to achieve the naive pluripotent state and remain primed for differentiation because of a failure to suppress fibroblast growth factor (FGF)/extracellular signal-regulated kinases (ERK) signaling. Although the mutant cells display marked genomic hypermethylation, suppression of FGF/ERK signaling by AICDA is independent of deaminase activity. Thus, our study identifies AICDA as a novel regulator of naive pluripotency through its activity on FGF/ERK signaling. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Related Products of 219580-11-7).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Related Products of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Epigenetic Regulation of Wnt Signaling by Carboxamide-Substituted Benzhydryl Amines that Function as Histone Demethylase Inhibitors was written by Zhang, Wen;Sviripa, Vitaliy M.;Xie, Yanqi;Yu, Tianxin;Haney, Meghan G.;Blackburn, Jessica S.;Adeniran, Charles A.;Zhan, Chang-Guo;Watt, David S.;Liu, Chunming. And the article was included in iScience in 2020.HPLC of Formula: 1373422-53-7 The following contents are mentioned in the article:

Aberrant activation of Wnt signaling triggered by mutations in either Adenomatous Polyposis Coli (APC) or CTNNB1 (å°?catenin) is a hallmark of colorectal cancers (CRC). As part of a program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing either aryl or heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors of the Wnt pathway. A biotinylated variant of N-((5-chloro-8-hydroxyquinolin-7-yl) (4-(diethylamino)phenyl)-methyl)butyramide (CBA-1) identified KDM3A as a binding partner. KDM3A is a Jumonji (JmjC) domain-containing demethylase that is significantly upregulated in CRC. KDM3A regulates the demethylation of histone H3鈥瞫 lysine 9 (H3K9Me2), a repressive marker for transcription. Inhibiting KDM3 increased H3K9Me2 levels, repressed Wnt target genes, and curtailed in vitro CRC cell proliferation. CBA-1 also exhibited in vivo inhibition of Wnt signaling in a zebrafish model without displaying in vivo toxicity. This study involved multiple reactions and reactants, such as 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7HPLC of Formula: 1373422-53-7).

3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.HPLC of Formula: 1373422-53-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fibroblast growth factor receptor inhibitors was written by Suneel Kumar, B. V. S.;Narasu, Lakshmi;Gundla, Rambabu;Dayam, Raveendra;Sarma, J. A. R. P.. And the article was included in Current Pharmaceutical Design in 2013.Electric Literature of C28H41N7O3 The following contents are mentioned in the article:

A review. Fibroblast growth factor receptors (FGFRs) play an important role in embryonic development, angiogenesis, wound healing, cell proliferation and differentiation. The fibroblast growth factor receptor (FGFR) isoforms have been under intense scrutiny for effective anticancer drug candidates. The fibroblast growth factor (FGF) and its receptor (FGFR) provide another pathway that seems critical to monitoring angiogenesis. Recent findings suggest that FGFR mediates signaling, regulates the PKM2 activity, and plays a crucial role in cancer metabolism The current review also covers the recent findings on the role of FGFR1 in cancer metabolism This paper reviews the progress, mechanism, and binding modes of recently known kinase inhibitors such as PD173074, SU series and other inhibitors still under clin. development. Some of the structural classes that will be highlighted in this review include Pyrido[2,3-d]pyrimidines, Indolin-2-one, Pyrrolo[2,1-f][1,2,4]triazine, Pyrido[2,3-d]pyrimidin-7(8H)-one, and 1,6-Naphthyridin-2(1H)-ones. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Electric Literature of C28H41N7O3).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Electric Literature of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of H3K4 demethylation induces autophagy in cancer cell lines was written by Wang, Zhen;Long, Qiao-Yun;Chen, Lin;Fan, Jia-Dong;Wang, Zhao-Ning;Li, Lian-Yun;Wu, Min;Chen, Xuefeng. And the article was included in Biochimica et Biophysica Acta, Molecular Cell Research in 2017.COA of Formula: C24H27N5O2 The following contents are mentioned in the article:

Epigenetic factors and related small mols. have emerged to be strongly involved in autophagy process. Here we report that 2-PCPA and GSK-LSD1, two inhibitors of histone H3K4 demethylase KDM1A/LSD1, induce autophagy in multiple mammalian cell lines. The two small mols. induce accumulation of LC3II, formation of autophagosome and autolysosome, and SQSTM1/p62 degradation 2-PCPA treatment inhibits cell proliferation through cell cycle arrest but does not inducing cell death. Exogenous expression of KDM1A/LSD1 impaired the autophagic phenotypes triggered by 2-PCPA. The autophagy induced by 2-PCPA requires LC3-II processing machinery. But depletion of BECN1 and ULK1 with siRNA did not affect the LC3-II accumulation triggered by 2-PCPA. 2-PCPA treatment induces the change of global gene expression program, including a series of autophagy-related genes, such as SQSTM1/p62. Taken together, our data indicate that KDM1A/LSD1 inhibitors induce autophagy through affecting the expression of autophagy-related genes and in a BECN1-independent manner. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0COA of Formula: C24H27N5O2).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.COA of Formula: C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response was written by Amin, Ruhul;Shukla, Anjali;Zhu, Jacqueline Jufen;Kim, Sohyoung;Wang, Ping;Tian, Simon Zhongyuan;Tran, Andy D.;Paul, Debasish;Cappell, Steven D.;Burkett, Sandra;Liu, Huaitian;Lee, Maxwell P.;Kruhlak, Michael J.;Dwyer, Jennifer E.;Simpson, R. Mark;Hager, Gordon L.;Ruan, Yijun;Hunter, Kent W.. And the article was included in Nature Communications in 2021.Application of 1373423-53-0 The following contents are mentioned in the article:

Mech. signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor pos. (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Application of 1373423-53-0).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Application of 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Morphological screening of mesenchymal mammary tumor organoids to identify drugs that reverse epithelial-mesenchymal transition was written by Zhao, Na;Powell, Reid T.;Yuan, Xueying;Bae, Goeun;Roarty, Kevin P.;Stossi, Fabio;Strempfl, Martina;Toneff, Michael J.;Johnson, Hannah L.;Mani, Sendurai A.;Jones, Philip;Stephan, Clifford C.;Rosen, Jeffrey M.. And the article was included in Nature Communications in 2021.HPLC of Formula: 1373423-53-0 The following contents are mentioned in the article:

The epithelial-mesenchymal transition (EMT) has been implicated in conferring stem cell properties and therapeutic resistance to cancer cells. Therefore, identification of drugs that can reprogram EMT may provide new therapeutic strategies. Here, we report that cells derived from claudin-low mammary tumors, a mesenchymal subtype of triple-neg. breast cancer, exhibit a distinctive organoid structure with extended “spikes” in 3D matrixes. Upon a miR-200 induced mesenchymal-epithelial transition (MET), the organoids switch to a smoother round morphol. Based on these observations, we developed a morphol. screening method with accompanying anal. pipelines that leverage deep neural networks and nearest neighborhood classification to screen for EMT-reversing drugs. Through screening of a targeted epigenetic drug library, we identified multiple class I HDAC inhibitors and Bromodomain inhibitors that reverse EMT. These data support the use of morphol. screening of mesenchymal mammary tumor organoids as a platform to identify drugs that reverse EMT. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0HPLC of Formula: 1373423-53-0).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.HPLC of Formula: 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The hepatotoxic potential of protein kinase inhibitors predicted with Random Forest and Artificial Neural Networks was written by Schoning, Verena;Krahenbuhl, Stephan;Drewe, Jurgen. And the article was included in Toxicology Letters in 2018.Name: 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea The following contents are mentioned in the article:

Protein kinases (PKs) play a role in many pivotal aspects of cellular function. Dysregulation and mutations of protein kinases are involved in the development of different diseases, which might be treated by inhibition of the corresponding kinase. Protein kinase inhibitors (PKIs) are generally well tolerated, but unexpected and serious adverse events on the heart, lung, kidney and liver were observed clin. In this study, the structure-activity relationship of PKIs in relation to hepatotoxicity was investigated. A dataset of 165 PKIs was compiled and the probability of human hepatotoxicity with two different machine learning algorithms (Random Forest and Artificial Neural Networks) was analyzed. The estimated probability of hepatotoxicity was generally high for single PKIs. However, depending on the target kinase of the PKI, a difference in hepatotoxic potential could be observed The similarity of the PKIs to each other is caused by the conserved site of action of the protein kinases. Hepatotoxicity may therefore always be an issue in PKIs. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Name: 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Pyrimidine derivatives have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.Name: 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SHMT2 and the BRCC36/BRISC deubiquitinase regulate HIV-1 Tat K63-ubiquitylation and destruction by autophagy was written by Xu, Muyu;Moresco, James J.;Chang, Max;Mukim, Amey;Smith, Davey;Diedrich, Jolene K.;Yates, John R. III;Jones, Katherine A.. And the article was included in PLoS Pathogens in 2018.Computed Properties of C22H23N5O2 The following contents are mentioned in the article:

HIV-1 Tat is a key regulator of viral transcription, however little is known about the mechanisms that control its turnover in T cells. Here we use a novel proteomics technique, called DiffPOP, to identify the mol. target of JIB-04, a small mol. compound that potently and selectively blocks HIV-1 Tat expression, transactivation, and virus replication in T cell lines. Mass-spectrometry anal. of whole-cell extracts from 2D10 Jurkat T cells revealed that JIB-04 targets Serine Hydroxymethyltransferase 2 (SHMT2), a regulator of glycine biosynthesis and an adaptor for the BRCC36 K63Ub-specific deubiquitinase in the BRISC complex. Importantly, knockdown of SHMT1,2 or BRCC36, or exposure of cells to JIB-04, strongly increased Tat K63Ub-dependent destruction via autophagy. Moreover, point mutation of multiple lysines in Tat, or knockdown of BRCC36 or SHMT1,2, was sufficient to prevent destruction of Tat by JIB-04. We conclude that HIV-1 Tat levels are regulated through K63Ub-selective autophagy mediated through SHMT1,2 and the BRCC36 deubiquitinase. This study involved multiple reactions and reactants, such as 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7Computed Properties of C22H23N5O2).

3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Computed Properties of C22H23N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity was written by Schniewind, Inaki;Hadiwikarta, Wahyu Wijaya;Grajek, Julia;Poleszczuk, Jan;Richter, Susan;Peitzsch, Mirko;Mueller, Johannes;Klusa, Daria;Beyreuther, Elke;Loeck, Steffen;Luehr, Armin;Frosch, Susanne;Groeben, Christer;Sommer, Ulrich;Krause, Mechthild;Dubrovska, Anna;von Neubeck, Claere;Kurth, Ina;Peitzsch, Claudia. And the article was included in Cell Reports in 2022.Application of 1373422-53-7 The following contents are mentioned in the article:

Proton radiotherapy has been implemented into the standard-of-care for cancer patients within recent years. However, exptl. studies investigating cellular and mol. mechanisms are lacking, and prognostic biomarkers are needed. Cancer stem cell (CSC)-related biomarkers, such as aldehyde dehydrogenase (ALDH), are known to influence cellular radiosensitivity through inactivation of reactive oxygen species, DNA damage repair, and cell death. In a previous study, we found that ionizing radiation itself enriches for ALDH-pos. CSCs. In this study, we analyze CSC marker dynamics in prostate cancer, head and neck cancer, and glioblastoma cells upon proton beam irradiation We find that proton irradiation has a higher potential to target CSCs through induction of complex DNA damages, lower rates of cellular senescence, and minor alteration in histone methylation pattern compared with conventional photon irradiation Math. modeling indicates differences in plasticity rates among ALDH-pos. CSCs and ALDH-neg. cancer cells between the two irradiation types. This study involved multiple reactions and reactants, such as 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7Application of 1373422-53-7).

3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Application of 1373422-53-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia