Category: pyrimidines

Gadolinium chloride inhibition of rat hepatic microsomal epoxide hydrolase and glutathione S-transferase gene expression was written by Kim, Sang Geon;Choi, Sung Hee. And the article was included in Drug Metabolism and Disposition in 1997.Reference of 39083-15-3 The following contents are mentioned in the article:

The effects of gadolinium chloride, a Kupffer cell toxicant, on the constitutive and inducible expression of hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) genes were examined in rats. Northern blot anal. showed that treatment of rats with GdCl₃ caused suppression of mEH and GST gene expression. MEH mRNA levels were decreased in a time-dependent manner after a single injected dose of GdCl₃ (10 mg/kg, i.v.), resulting in 95, 55, 17, 36, and 69% of the levels in untreated animals at 6, 12, 18, 24, and 48 h after treatment, resp. A maximal reduction in GST Ya, Yb1/2, and Yc1 mRNA levels was also noted at 18 h after treatment with GdCl₃, followed by a gradual return to levels in untreated rats at later time points. Whereas treatment of rats with thiazole, allyl disulfide, Pr sulfide, oltipraz, or clotrimazole caused 2-13-fold increases in mEH mRNA levels at 18 h after treatment, concomitant GdCl₃ treatment caused 30-70% reductions in the increases in mEH mRNA levels. The chem.-inducible mRNA levels for GST Ya, Yb1/2, and Yc1 were also significantly inhibited by GdCl₃ at 18 h after treatment. Rats treated with GdCl₃ (10 mg/kg/day, i.v.) for 3-5 consecutive days exhibited 40-90% decreases in mEH, GST Ya, and GST Yb1/2 mRNA levels, relative to control, whereas the Yc1 mRNA level was suppressed at early times and returned to levels in untreated animals at day 5 after treatment. The mRNA levels for mEH and GST Ya in rats treated daily with both allyl disulfide (25 mg/kg, po) and GdCl₃ for 3 consecutive days were 20-30% of those in rats treated with allyl disulfide alone. Western immunoblotting showed that mEH and GST Ya protein expression was decreased at 1-3 days after consecutive daily treatment with GdCl₃. Whereas treatment of rats with GdCl₃ at a dose of 1 mg/kg suppressed constitutive hepatic mEH gene expression by 85% at 18 h, rats treated with CaCl₂ (10 mg/kg, i.v.) in combination with GdCl₃ (1 mg/kg, i.v.) showed 45% suppression of the mEH mRNA level, compared with untreated animals. GdCl₃-induced suppression was also significantly reversed for GST Ya mRNA by excessive CaCl₂ administration. These results demonstrate that GdCl₃ effectively inhibits constitutive and inducible mEH and GST expression, with decreases in their mRNA levels. GdCl₃ suppression of detoxifying enzyme expression may be associated with its blocking of intracellular Ca²⁺ influx, which affects signaling pathways for the expression of the genes. This study involved multiple reactions and reactants, such as 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3Reference of 39083-15-3).

5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. 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.Reference of 39083-15-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Cross-suppression of EGFR ligands amphiregulin and epiregulin and de-repression of FGFR3 signalling contribute to cetuximab resistance in wild-type KRAS tumour cells was written by Oliveras-Ferraros, C.;Cufi, S.;Queralt, B.;Vazquez-Martin, A.;Martin-Castillo, B.;de Llorens, R.;Bosch-Barrera, J.;Brunet, J.;Menendez, J. A.. And the article was included in British Journal of Cancer in 2012.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:

BACKGROUND: In addition to the mutational status of KRAS, the epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG) might function as bona fide biomarkers of cetuximab (Ctx) sensitivity for most EGFR-driven carcinomas. METHODS: Lentivirus-delivered small hairpin RNAs were employed to specifically reduce AREG or EREG gene expression in wild-type KRAS A431 squamous cell carcinoma cells. Colony-forming assays were used to monitor the impact of AREG and EREG knockdown on Ctx efficacy. Amphiregulin and EREG protein expression levels were assessed by quant. ELISA in parental A431 cells and in pooled populations of A431 cells adapted to grow in the presence of Ctx. A phosphoproteomic platform was used to measure the relative level of phosphorylation of 42 distinct receptor tyrosine kinases before and after the acquisition of resistance to Ctx. RESULTS: Stable gene silencing of either ligand was found to notably reduce the expression of the other ligand. Parental A431 cells with normal expression levels of AREG/EREG exhibited significantly increased growth inhibition in response to Ctx, compared with derivatives that are engineered to produce minimal AREG/EREG. The parental A431 cells acutely treated with Ctx exhibited reduced basal expression levels of AREG/EREG. Pooled populations of Ctx-resistant A431 cells expressed significantly lower levels of AREG/EREG and were insensitive to the downregulatory effects of Ctx. Phosphoproteomic screen identified a remarkable hyperactivation of FGFR3 in Ctx-resistant A431 cells, which gained sensitivity to the cytotoxic and apoptotic effects of the FGFR3 TK inhibitor PD173074. The A431 parental cells acutely treated with Ctx rapidly activated FGFR3 and their concomitant exposure to Ctx and PD173074 resulted in synergistic apoptosis. CONCLUSION: Cross-suppression of AREG/EREG expression may explain the tight co-expression of AREG and EREG, as well as their tendency to be more highly expressed than other EGFR ligands to determine Ctx efficacy. The pos. selection for Ctx-resistant tumor cells exhibiting AREG/EREG cross-suppression may have an important role in the emergence of Ctx resistance. As de-repression of FGFR3 activity rapidly replaces the loss of EGFR-ligand signalling in terms of cell proliferation and survival, combinations of Ctx and FGFR3-targeted drugs may be a valuable strategy to enhance the efficacy of single Ctx while preventing or delaying acquired resistance to Ctx. British Journal of Cancer (2012) 106, 1406-1414. doi:10.1038/bjc.2012.103 www.bjcancer.com. 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 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.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

Relation between goitrogenic effect and chemical constitution was written by Jensen, K. A.;Kjerulf-Jensen, K.. And the article was included in Acta Pharmacologica et Toxicologica in 1945.Name: 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one The following contents are mentioned in the article:

In young rats, benzenesulfonic acid, phenyl p-toluenesulfonate, p-toluenesulfonamide, taurine, N⁴-(o-carboxybenzoyl)sulfathiazole, Na salt of N⁴-(1-sulfoethyl)sulfathiazole, p-tolyl isothiocyanate, ethylene dithiocyanate, mercaptoacetic acid, cysteine, mercaptosuccinic acid, p-toluenethiol, o-mercaptobenzoic acid, dibenzyl sulfide, bis(2-carboxyethyl) sulfide, α,α’-(thiocarbonyldithio)bis[glycolic acid], thioacetamide, thiobenzamide, xanthogenamide (H₂NC(:S)OEt), Et thionocarbanilate, N-allyl-N’-(m-carboxyphenyl)thiourea, selenourea, 2-methyl-2-thiopseudourea sulfate, thiosemicarbazide, 4-allylthiosemicarbazide, hydrazodithiodicarboxamide, 1,3-oxalylthiourea (thioparabanic acid), 1,3-ethylenethiocarbamide (2-thioxoimidazolidine), 2(3)-benzimidazolethione, 2-imino-4-thiazolidone-5-acetic acid, 5-imino-3-thioxo-1,2,4-dithiazolidine, 2-aminothiazole, thioammeline, 2-amino-4-methyl-6-mercaptopyrimidine, 6-methyl-4-thiouracil, 5-methyl-2-thiouracil (thiothymine), 6-methyluracil, 6-amino-2-thiouracil, 2-amino-4-hydroxy-6-methylpyrimidine, 2-mercapto-4-methyl-6-aminopyrimidine, 2-mercapto-4,6-dimethylpyrimidine, 2-methylmercapto-4-mercapto-6-methylpyrimidine, 2-mercapto-4-phenyl-6-methylpyrimidine, compound (1:1) of NH₃ and 6-imino-5-isonitroso-2-thiouracil, 2-thio-5-aminobarbituric acid (thiouramil), 2-thio-5-ethylbarbituric acid, 2-thioxanthine, 2-thiopseudouric acid, dithiohydurilic acid, 2,4-dioxothiazolidine, 1,4-dithiane, s-trithiane, phenothiazine, biuret, biguanide, dicyandiamidine, thiodicyandiamidine, 1-phenylsemicarbazide, benzoylacetone, salicylaldehyde oxime, β-isatin oxime, dimethylglyoxime, 5-isonitrosobarbituric (violuric) acid, 1-phenyl-3-methyl-4-isonitroso-5-pyrazolone, salicylaldehyde phenylhydrazone, glyoxal osazone, 8-hydroxyquinoline, triphenylphosphine, triphenylarsine, K xanthate, Na diethyldithiocarbamate, KCN, Na₂S, and Na₂S₂O₃ had no goitrogenic action. Sulfaguanidine, sulfonal, dithioöxamide, thiourea, allylthiourea, 1,3-diphenylthiourea, 2-thiohydantoin, 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazoline, 1,3-(1,8-naphthylene)thiourea, thioantipyrine, and p-aminobenzoic acid were weakly goitrogenic or of doubtful effect. Methylthiourea, trimethylthiourea, tetramethylthiourea, dithizone, 6-methyl-2-thiouracil, 6-methyl-5-ethyl-2-thiouracil, 6-methyl-5-butyl-2-thiouracil (m. 189°, preparation described), 6-methyl-5-isoamyl-2-thiouracil (m. 222-3°, preparation given), and 4-phenyl-2-thiouracil were strongly goitrogenic. This study involved multiple reactions and reactants, such as 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3Name: 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one).

5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (cas: 39083-15-3) 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 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: 5-Ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays was written by Lobo-Silva, Jessica;Cabral, Fernanda J.;Amaral, Murilo S.;Miyasato, Patricia A.;de Freitas, Rafaela Paula;Pereira, Adriana S. A.;Khouri, Mariana I.;Barbosa, Mayra M. F.;Ramos, Pablo I. P.;Leite, Luciana C. C.;Asojo, Oluwatoyin A.;Nakano, Eliana;Verjovski-Almeida, Sergio;Farias, Leonardo P.. And the article was included in Parasites & Vectors in 2020.Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate The following contents are mentioned in the article:

Abstract: Background: Schistosomiasis chemotherapy is largely based on praziquantel (PZQ). Although PZQ is very safe and tolerable, it does not prevent reinfection and emerging resistance is a primary concern. Recent studies have shown that the targeting of epigenetic machinery in Schistosoma mansoni may result in severe alterations in parasite development, leading to death. This new route for drug discovery in schistosomiasis has focused on classes of histone deacetylases (HDACs) and histone acetyltransferases (HATs) as epigenetic drug targets. Schistosoma histone demethylases also seem to be important in the transition of cercariae into schistosomula, as well as sexual differentiation in adult worms. Methods: The Target-Pathogen database and mol. docking assays were used to prioritize the druggability of S. mansoni histone demethylases. The transcription profile of Smp_03400 was re-analyzed using available databases. The effect of GSK-J4 inhibitor in schistosomula and adult worms’ motility/viability/oviposition was assessed by in vitro assays. Ultrastructural anal. was performed on adult worms exposed to GSK-J4 by SEM, while internal structures and muscle fiber integrity was investigated by confocal microscopy after Langeron’s carmine or phalloidin staining. Results: The present evaluation of the potential druggability of 14 annotated S. mansoni demethylase enzymes identified the S. mansoni ortholog of human KDM6A/UTX (Smp_034000) as the most suitable druggable target. In silico anal. and mol. modeling indicated the potential for cofactor displacement by the chem. probe GSK-J4. Our re-anal. of transcriptomic data revealed that Smp_034000 expression peaks at 24 h in newly transformed schistosomula and 5-wk-old adult worms. Moreover, this gene was highly expressed in the testes of mature male worms compared to the rest of the parasite body. In in vitro schistosome cultures, treatment with GSK-J4 produced striking effects on schistosomula mortality and adult worm motility and mortality, as well as egg oviposition, in a dose- and time-dependent manner. Unexpectedly, western blot assays did not demonstrate overall modulation of H3K27me3 levels in response to GSK-J4. Confocal and SEM revealed the loss of original features in muscle fibers and alterations in cell-cell contact following GSK-J4 treatment. Conclusions: GSK-J4 presents promising potential for antischistosomal control; however, the underlying mechanisms warrant further investigation.[graphic not available: see fulltext]. 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: 1373423-53-0Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate).

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. 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.Name: Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

KDM6B epigenetically regulated-interleukin-6 expression in the dorsal root ganglia and spinal dorsal horn contributes to the development and maintenance of neuropathic pain following peripheral nerve injury in male rats was written by Li, Liren;Bai, Liying;Yang, Kangli;Zhang, Jian;Gao, Yan;Jiang, Mingjun;Yang, Yin;Zhang, Xuan;Wang, Li;Wang, Xueli;Qiao, Yiming;Xu, Ji-Tian. And the article was included in Brain, Behavior, and Immunity in 2021.Category: pyrimidines The following contents are mentioned in the article:

The lysine specific demethylase 6B (KDM6B) has been implicated as a coregulator in the expression of proinflammatory mediators, and in the pathogenesis of inflammatory and arthritic pain. However, the role of KDM6B in neuropathic pain has yet to be studied. In the current study, the neuropathic pain was determined by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) following lumbar 5 spinal nerve ligation (SNL) in male rats. Immunohistochem., Western blotting, qRT-PCR, and chromatin immunoprecipitation (ChIP)-PCR assays were performed to investigate the underlying mechanisms. Our results showed that SNL led to a significant increase in KDM6B mRNA and protein in the ipsilateral L4/5 dorsal root ganglia (DRG) and spinal dorsal horn; and this increase correlated a markedly reduction in the level of H3K27me3 methylation in the same tissue. Double immunofluorescence staining revealed that the KDM6B expressed in myelinated A- and unmyelinated C-fibers in the DRG; and located in neuronal cells, astrocytes, and microglia in the dorsal horn. Behavioral data showed that SNL-induced mech. allodynia and thermal hyperalgesia were impaired by the treatment of prior to i.t. injection of GSK-J4, a specific inhibitor of KDM6B, or KDM6B siRNA. Both microinjection of AAV2-EGFP-KDM6B shRNA in the lumbar 5 dorsal horn and sciatic nerve, sep., alleviated the neuropathic pain following SNL. The established neuropathic pain was also partially attenuated by repeat i.t. injections of GSK-J4 or KDM6B siRNA, started on day 7 after SNL. SNL also resulted in a remarkable increased expression of interleukin-6 (IL-6) in the DRG and dorsal horn. But this increase was dramatically inhibited by i.t. injection of GSK-J4 and KDM6B siRNA; and suppressed by prior to microinjection of AAV2-EGFP-KDM6B shRNA in the dorsal horn and sciatic nerve. Of ChIP-PCR assay showed that SNL-induced enhanced binding of STAT3 with IL-6 promoter was inhibited by prior to i.t. injection of GSK-J4. Meanwhile, the level of H3K27me3 methylation was also decreased by the treatment. Together, our results indicate that SNL-induced upregulation of KDM6B via demethylating H3K27me3 facilitates the binding of STAT3 with IL-6 promoter, and subsequently mediated-increase in the expression of IL-6 in the DRG and dorsal horn contributes to the development and maintenance of neuropathic pain. Targeting KDM6B might a promising therapeutic strategy to treatment of chronic pain. 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: 1373423-53-0Category: pyrimidines).

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 nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Functional coculture of sympathetic neurons and cardiomyocytes derived from human-induced pluripotent stem cells was written by Winbo, Annika;Ramanan, Suganeya;Eugster, Emily;Jovinge, Stefan;Skinner, Jonathan R.;Montgomery, Johanna M.. And the article was included in American Journal of Physiology in 2020.SDS of cas: 219580-11-7 The following contents are mentioned in the article:

Sympathetic neurons (SNs) capable of modulating the heart rate of murine cardiomyocytes (CMs) can be differentiated from human stem cells. The electrophysiol. properties of human stem cell-derived SNs remain largely uncharacterized, and human neurocardiac cocultures remain to be established. Here, we have adapted previously published differentiation and coculture protocols to develop feeder-free SNs using human-induced pluripotent stem cells (hiPSCs). HiPSC-SNs were characterized in monoculture and coculture with hiPSC-CMs, using antibody labeling, ELISA, and whole cell patch-clamp electrophysiol. techniques. HiPSC-SNs stained pos. for peripherin, tyrosine hydroxylase, and nicotinic acetylcholine receptors, the latter two colocalizing in somas and synaptic varicosities. hiPSC-SNs functionally matured in vitro and exhibited healthy resting membrane potentials (average-61 ± 0.7 mV), secreted norepinephrine upon activation, and generated synaptic and action currents and inward and outward voltage-dependent currents. All hiPSC-SNs fired action potentials in response to current injection, local application of potassium, or spontaneously, followed by short-medium afterhyperpolarizations. A HiPSC-SNs could successfully be maintained in coculture with hiPSC-CMs, and this induced further development of hiPSC-SN action potential kinetics. To test functional coupling between the neurons and cardiomyocytes, the hiPSC-CM beating response to nicotine-induced norepinephrine release was assessed. In neurocardiac cocultures, nicotine exposure significantly increased the hiPSC-CM spontaneous beating rate, but not in hiPSC-CM monocultures, supporting nicotinic neuronal hiPSC-SN stimulation directly influencing hiPSC-CM function. Our data show the development and characterization of electrophysiol. functional hiPSC-SNs capable of modulating the beating rate of hiPSC-CMs in vitro. These human cocultures provide a novel multicellular model to study neurocardiac modulation under physiol. and pathol. conditions. NEW ± NOTEWORTHY We present data on a functional coculture between human-induced pluripotent stem cell-derived sympathetic neurons and cardiomyocytes. Moreover, this study adds significantly to the available data on the electrophysiol. function of humaninduced pluripotent stem cell-derived sympathetic neurons. human-induced pluripotent stem cells; neurocardiac coculture; sympathetic modulation of heart rate; sympathetic neurons. 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: 219580-11-7SDS of cas: 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 ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. 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.SDS of cas: 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The effect of basic fibroblast growth factor 2 on the bovine corpus luteum depends on the stage of the estrous cycle and modulates prostaglandin F_2α action was written by Piotrowska-Tomala, K. K.;Jonczyk, A. W.;Kordowitzki, P.;Jalali, B. M.;Skarzynski, D. J.. And the article was included in Animal in 2021.COA of Formula: C28H41N7O3 The following contents are mentioned in the article:

The roles of fibroblast growth factor 2 (FGF2) in the corpus luteum (CL) function and its modulatory effect on prostaglandin (PG) F_2α during the bovine estrous cycle were studied using the following design of in vivo and in vitro experiments: (1) effects of FGF2 and FGF receptor 1 inhibitor (PD173074) on bovine CL function in the early (PGF_2α-resistant) and mid (PGF_2α-responsive) luteal stage in vivo, (2) the modulatory effect of FGF2 on PGF_2α action during the luteal phase in vivo and (3) effects of FGF2 and PD173074 on bovine CL secretory function in vitro. Cows were treated by injection into the CL with: (1) saline (control), (2) FGF2, (3) PD173074, (4) FGF2 followed by i.m. (i.m.) PGF_2α, (5) PD173074 followed by i.m. PGF_2α and (6) i.m. PGF_2α as a pos. control. For in vitro experiments, CL explants were treated with the aforementioned factors. Progesterone (P₄) concentrations of blood samples or culture media were determined by RIA. Relative mRNA expressions of the genes involved in angiogenesis and steroidogenesis were determined by quant. real-time PCR. Although FGF2 treatment on day 4 of the estrous cycle did not change the cycle length, FGF2 with PGF_2α decreased the P₄ concentrations observed during the estrous cycle compared to the control group (P < 0.001). Moreover, FGF2 treatment on day 10 prolonged CL function as indicated by a significantly greater concentration of P₄ on day 21 compared to the control group. In the in vitro study, FGF2 decreased cytochrome P 450 family 11 subfamily A member 1 (CYP11A1) and hydroxy-delta-5-steroid dehydrogenase (HSD3B1) mRNA expression (P < 0.01) and decreased P₄ production in the early-stage CL (P < 0.001). However, FGF2 + PGF_2α or PGF_2α alone resulted in an elevation of steroidogenic acute regulatory protein and CYP11A1 mRNA expression and P₄ secretion in the early-stage CL (P < 0.01). In the mid-luteal phase, FGF2 upregulated CYP11A1 and HSD3B1 mRNA expression (P < 0.01), while FGF2 + PGF_2α increased only HSD3B1 mRNA expression (P < 0.001). In conclusion, FGF2 seems to play a modulatory role in CL development or luteolysis, differentially regulating steroidogenesis and angiogenic factors as well as PGF_2α actions. 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: 219580-11-7COA of Formula: 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. 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. 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.COA of Formula: C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma was written by Saito, Shin;Morishima, Kazue;Ui, Takashi;Hoshino, Hiroko;Matsubara, Daisuke;Ishikawa, Shumpei;Aburatani, Hiroyuki;Fukayama, Masashi;Hosoya, Yoshinori;Sata, Naohiro;Lefor, Alan K.;Yasuda, Yoshikazu;Niki, Toshiro. And the article was included in BMC Cancer in 2015.Recommanded Product: 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:

Background: Although advanced esophageal squamous-cell carcinoma (ESCC) is treated using a multidisciplinary approach, outcomes remain unsatisfactory. The microenvironment of cancer cells has recently been shown to strongly influence the biol. properties of malignancies. We explored the effect of supernatant from esophageal fibroblasts on the cell growth and chemo-resistance of ESCC cell lines. Methods: We used 22 ESCC cell lines, isolated primary human esophageal fibroblasts and immortalized fibroblasts. We first examined cell proliferation induced by fibroblast supernatant. The effect of supernatant was evaluated to determine whether paracrine signaling induced by fibroblasts can influence the proliferation of cancer cells. Next, we examined the effects of adding growth factors HGF, FGF1, FGF7, and FGF10, to the culture medium of cancer cells. These growth factors are assumed to be present in the culture supernatants of fibroblasts and may exert a paracrine effect on the proliferation of cancer cells. We also examined the intrinsic role of HGF/MET and FGFs/FGFR in ESCC proliferation. In addition, we examined the inhibitory effect of lapatinib on ESCC cell lines and studied whether the fibroblast supernatants affect the inhibitory effect of lapatinib on ESCC cell proliferation. Finally, we tested whether the FGFR inhibitor PD-173074 could eliminate the rescue effect against lapatinib that was induced by fibroblast supernatants. Results: The addition of fibroblast supernatant induces cell proliferation in the majority of cell lines tested. The results of experiments to evaluate the effects of adding growth factors and kinase inhibitors suggests that the stimulating effect of fibroblasts was attributable in part to HGF/MET or FGF/FGFR. The results also indicate diversity in the degree of dependence on HGF/MET and FGF/FGFR among the cell lines. Though lapanitib at 1 μM inhibits cell proliferation by more than 50% in the majority of the ESCC cell lines, fibroblast supernatant can rescue the growth inhibition of ESCC cells. However, the rescue effect is abrogated by co-treatment with FGFR inhibitor. Conclusion: These results demonstrate that cell growth of ESCC depends on diverse receptor tyrosine kinase signaling, in both cell-autonomous and cell-non-autonomous manners. The combined inhibition of these signals may hold promise for the treatment of ESCC. 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: 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. 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. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Recommanded Product: 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

Centrally circulating α-klotho inversely correlates with human obesity and modulates arcuate cell populations in mice was written by Landry, Taylor;Li, Peixin;Shookster, Daniel;Jiang, Zhiying;Li, Hongli;Laing, Brenton Thomas;Bunner, Wyatt;Langton, Theodore;Tong, Qingchun;Huang, Hu. And the article was included in Molecular Metabolism in 2021.Electric Literature of C28H41N7O3 The following contents are mentioned in the article:

Our laboratory recently identified the centrally circulating α-klotho protein as a novel hypothalamic regulator of food intake and glucose metabolism in mice. The current study aimed to investigate novel mol. effectors of central α-klotho in the arcuate nucleus of the hypothalamus (ARC), while further deciphering its role regulating energy balance in both humans and mice.Cerebrospinal fluid (CSF) was collected from 22 adults undergoing lower limb orthopedic surgeries, and correlations between body weight and α-klotho were determined using an α-klotho ELISA (ELISA) kit. To investigate the effects of α-klotho on energy expenditure (EE), 2-day intracerebroventricular (ICV) treatment was performed in diet-induced obesity (DIO) mice housed in TSE Phenomaster indirect calorimetry metabolic cages. Immunohistochem. staining for cFOS and patch clamp electrophysiol. were used to determine the effects of central α-klotho on proopiomelanocortin (POMC) and tyrosine hydroxylase (TH) neurons. Addnl. stainings were performed to determine novel roles for central α-klotho to regulate non-neuronal cell populations in the ARC. Lastly, ICV pretreatment with fibroblast growth factor receptor (FGFR) or PI3kinase inhibitors was performed to determine the intracellular signaling involved in α-klotho-mediated regulation of ARC nuclei.Obese/overweight human subjects had significantly lower CSF α-klotho concentrations compared to lean counterparts (1,044 ± 251 vs. 1616 ± 218 pmol/L, resp.). Addnl., 2 days of ICV α-klotho treatment increased EE in DIO mice. α-Klotho had no effects on TH neuron activity but elicited varied responses in POMC neurons, with 44% experiencing excitatory and 56% experiencing inhibitory effects. Inhibitor experiments identified an α-klotho→FGFR→PI3kinase signaling mechanism in the regulation of ARC POMC and NPY/AgRP neurons. Acute ICV α-klotho treatment also increased phosphorylated ERK in ARC astrocytes via FGFR signaling.Our human CSF data provide the first evidence that impaired central α-klotho function may be involved in the pathophysiol. of obesity. Furthermore, results in mouse models identify ARC POMC neurons and astrocytes as novel mol. effectors of central α-klotho. Overall, the current study highlights prominent roles of α-klotho→FGFR→PI3kinase signaling in the homeostatic regulation of ARC neurons and whole-body energy balance. 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. 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.Electric Literature of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The N6-methylandenosine-related gene BIRC5 as a prognostic biomarker correlated with cell migration and immune cell infiltrates in low grade glioma was written by Jiang, Xiulin;Shi, Yulin;Chen, Xi;Xu, Haitao;Huang, Xiaobin;Li, Lihua;Pu, Jun. And the article was included in Frontiers in Molecular Biosciences in 2022.Related Products of 1373423-53-0 The following contents are mentioned in the article:

Gliomas account for 75% of all primary malignant brain tumors in adults and are associated with high mortality. Emerging evidence has demonstrated that baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays a critical role in cell apoptosis and the progression of diverse cancers. However, no studies have yet focused on the immunol. function and mechanisms of upstream BIRC5 regulation in the progression of low-grade gliomas (LGG). Here, author evaluated BIRC5 expression and clin. characteristics in people with LGG using the Chinese Glioma Genome Atlas, The Cancer Genome Atlas, Gene Expression Omnibus, Rembrandt, and Gravendeel databases. Author used Kaplan-Meier statistics and receiver operating characteristic (ROC) curves to analyze the prognostic value of BIRC5 in LGG. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontol. (GO) enrichment terms were also explored to identify functional roles of BIRC5. The Tumor Immune Estimation Resource (TIMER) and Tumor Immune System Interaction (TISIDB) databases were used to examine the correlation between BIRC5 expression and immune cell infiltration in LGG. The Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal (CTRP) databases were used to examine the potential drugs targeting BIRC5. Author used transwell and wound healing assays to determine the biol. functions of BIRC5 in glioma cell migration. Author results demonstrated that BIRC5 was highly expressed in LGG and the expression level correlated with tumor grade, prognosis, histol. subtype, isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q chromosomal co-deletion, chemotherapy status, and O[6]-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. GO and KEGG anal. showed that BIRC5 is primarily involved in cell proliferation and immune response-related signaling pathways. Author also found that BIRC5 was significantly correlated with m6A modification and diverse drug sensitivity. TIMER and TISIDB database anal. showed that BIRC5 expression is associated with infiltration of diverse immune cells and immune modulation in LGG. BIRC5 knockdown inhibited LGG cell migration. Collectively, author results demonstrate that BIRC5 is correlated with cell migration and immune infiltration in LGG and may be a useful prognostic biomarker. 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: 1373423-53-0Related Products 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 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.Related Products of 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia