Tag: 500-600

Predicting anticancer drug responses using a dual-layer integrated cell line-drug network model was written by Zhang, Naiqian;Wang, Haiyun;Fang, Yun;Wang, Jun;Zheng, Xiaoqi;Liu, X. Shirley. And the article was included in PLoS Computational Biology in 2015.Safety of 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:

The ability to predict the response of a cancer patient to a therapeutic agent is a major goal in modern oncol. that should ultimately lead to personalized treatment. Existing approaches to predicting drug sensitivity rely primarily on profiling of cancer cell line panels that have been treated with different drugs and selecting genomic or functional genomic features to regress or classify the drug response. Here, we propose a dual-layer integrated cell line-drug network model, which uses both cell line similarity network (CSN) data and drug similarity network (DSN) data to predict the drug response of a given cell line using a weighted model. Using the Cancer Cell Line Encyclopedia (CCLE) and Cancer Genome Project (CGP) studies as benchmark datasets, our single-layer model with CSN or DSN and only a single parameter achieved a prediction performance comparable to the previously generated elastic net model. When using the dual-layer model integrating both CSN and DSN, our predicted response reached a 0.6 Pearson correlation coefficient with observed responses for most drugs, which is significantly better than the previous results using the elastic net model. We have also applied the dual-layer cell line-drug integrated network model to fill in the missing drug response values in the CGP dataset. Even though the dual-layer integrated cell line-drug network model does not specifically model mutation information, it correctly predicted that BRAF mutant cell lines would be more sensitive than BRAF wild-type cell lines to three MEK1/2 inhibitors tested. 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: 219580-11-7Safety of 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 pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. 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.Safety of 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

Screening anti-tumor compounds from Ligusticum wallichii using cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry was written by Zhang, Tao;Ding, Yuanyuan;An, Hongli;Feng, Liuxin;Wang, Sicen. And the article was included in Journal of Separation Science in 2015.Related Products of 219580-11-7 The following contents are mentioned in the article:

Tyrosine 367 Cysteine-fibroblast growth factor receptor 4 cell membrane chromatog. combined with HPLC and mass spectrometry was developed. Tyrosine 367 Cysteine-HEK293 cells were used as the cell membrane stationary phase. The specificity and reproducibility of the cell membrane chromatog. was evaluated using 1-tert-butyl-3-{2-[4-(diethylamino)butylamino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl}urea, nimodipine and dexamethasone acetate. Then, anti-tumor components acting on Tyrosine 367 Cysteine-fibroblast growth factor receptor 4 were screened and identified from extracts of Ligusticum wallichii. Components from the extract were retained on the cell membrane chromatog. column. The retained fraction was directly eluted into HPLC with mass spectrometry system for separation and identification. Finally, Levistolide A was identified as an active component from Ligusticum wallichii extracts The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan colorimetric assay revealed that Levistolide A inhibits proliferation of overexpressing the mutated receptor cells with dose-dependent manner. Phosphorylation of fibroblast growth factor receptor 4 was also decrease under Levistolide A treatment. Flex dock simulation verified that Levistolide A could bind with the tyrosine kinase domain of fibroblast growth factor receptor 4. Therefore, Levistolide A screened by the cell membrane chromatog. combined with HPLC and mass spectrometry can arrest cell growth. In conclusion, the two-dimensional HPLC method can screen and identify potential anti-tumor ingredients that specifically act on the tyrosine kinase domain of the mutated fibroblast growth factor receptor 4. 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. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Related Products of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

FGF21 promotes functional recovery after hypoxic-ischemic brain injury in neonatal rats by activating the PI3K/Akt signaling pathway via FGFR1/β-klotho was written by Ye, Lixia;Wang, Xue;Cai, Chenchen;Zeng, Shanshan;Bai, Junjie;Guo, Kaiming;Fang, Mingchu;Hu, Jian;Liu, Huan;Zhu, Liyun;Liu, Fei;Wang, Dongxue;Hu, Yingying;Pan, Shulin;Li, Xiaokun;Lin, Li;Lin, Zhenlang. And the article was included in Experimental Neurology in 2019.Synthetic Route of C28H41N7O3 The following contents are mentioned in the article:

Perinatal asphyxia often results in neonatal cerebral hypoxia-ischemia (HI), which is associated with high mortality and severe long-term neurol. deficits in newborns. Currently, there are no effective drugs to mitigate the functional impairments post-HI. Previous studies have shown that fibroblast growth factor 21 (FGF21) has a potential neuroprotective effect against brain injury. However, the effect of FGF21 on neonatal HI brain injury is unclear. In the present study, both in vivo and in vitro models were used to assess whether recombinant human FGF21 (rhFGF21) could exert a neuroprotective effect after HI and explore the associated mechanism. The results showed that the rhFGF21 treatment remarkably reduced the infarct volume, ameliorated the body weight and improved the tissue structure after HI in neonatal rats. In addition, the rhFGF21 treatment lengthened the running endurance times in the rotarod test and decreased the mean escape latencies and increased the number of platform crossings in the Morris water maze test at 21 d post-HI insult. In contrast, the FGFR1 inhibitor PD173074 and PI3K inhibitor LY294002 partially reversed these therapeutic effects. In isolated primary cortical neurons, the rhFGF21 treatment protected primary neurons from oxygen-glucose deprivation (OGD) insult by inhibiting neuronal apoptosis and promoting neuronal survival. Both our in vivo and in vitro results reveal that rhFGF21 could inhibit neuronal apoptosis by activating the PI3K/Akt signaling pathway via FGF21/FGFR1/β-klotho complex formation. Therefore, rhFGF21 may be a promising therapeutic agent for promoting functional recovery after HI-induced neonatal brain injury. 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: 219580-11-7Synthetic Route 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.Synthetic Route of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Network-based Biased Tree Ensembles (NetBiTE) for Drug Sensitivity Prediction and Drug Sensitivity Biomarker Identification in Cancer was written by Oskooei, Ali;Manica, Matteo;Mathis, Roland;Martinez, Maria Rodriguez. And the article was included in Scientific Reports in 2019.HPLC of Formula: 219580-11-7 The following contents are mentioned in the article:

We present the Network-based Biased Tree Ensembles (NetBiTE) method for drug sensitivity prediction and drug sensitivity biomarker identification in cancer using a combination of prior knowledge and gene expression data. Our devised method consists of a biased tree ensemble that is built according to a probabilistic bias weight distribution. The bias weight distribution is obtained from the assignment of high weights to the drug targets and propagating the assigned weights over a protein-protein interaction network such as STRING. The propagation of weights, defines neighborhoods of influence around the drug targets and as such simulates the spread of perturbations within the cell, following drug administration. Using a synthetic dataset, we showcase how application of biased tree ensembles (BiTE) results in significant accuracy gains at a much lower computational cost compared to the unbiased random forests (RF) algorithm. We then apply NetBiTE to the Genomics of Drug Sensitivity in Cancer (GDSC) dataset and demonstrate that NetBiTE outperforms RF in predicting IC50 drug sensitivity, only for drugs that target membrane receptor pathways (MRPs): RTK, EGFR and IGFR signaling pathways. We propose based on the NetBiTE results, that for drugs that inhibit MRPs, the expression of target genes prior to drug administration is a biomarker for IC50 drug sensitivity following drug administration. We further verify and reinforce this proposition through control studies on, PI3K/MTOR signaling pathway inhibitors, a drug category that does not target MRPs, and through assignment of dummy targets to MRP inhibiting drugs and investigating the variation in NetBiTE accuracy. 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: 219580-11-7HPLC of Formula: 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 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. 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.HPLC of Formula: 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fibroblast growth factor 21 improves glucose homeostasis partially via down-regulation of Na⁺–D-glucose cotransporter SGLT1 in the small intestine was written by Wang, Nan;Li, Shuai;Guo, Xiao-chen;Li, Jun-yan;Ren, Gui-ping;Li, De-shan. And the article was included in Biomedicine & Pharmacotherapy in 2019.Recommanded Product: 219580-11-7 The following contents are mentioned in the article:

Fibroblast growth factor-21 (FGF-21), an endocrine hormone, is regarded as a therapeutic target for diabetes base on its potent effects on improving hyperglycemia. Sodium-dependent glucose cotransporter 1 (SGLT1) is mainly expressed in the small intestine (SI) for intestinal glucose absorption. It has been demonstrated that SGLT1 expression is increased in diabetes, which is thought to contribute to the rapidly rising postprandial blood glucose levels. Thus, we aim to examine whether FGF-21 regulates expression of intestinal SGLT1 in diabetes. The db/db mice were treated with insulin, low and high dose of FGF-21 for 5 wk and then measured changes in glucose metabolism, intestinal glucose absorption and SGLT1 expression. The results showed that FGF-21 improved glucose homeostasis, inhibited intestinal glucose uptake and reduced intestinal SGLT1 expression compared with insulin in db/db mice. To further explore the mechanism of effects of FGF-21 on SGLT1 expression. The murine intestinal epithelial MODE-K cells were treated with FGF-21 for 3 h, 6 h, 12 h and 24 h and then measured glucose uptake, SGLT1 expression, another glucose transporter GLUT2 expression and associated mechanism. Our results showed that FGF-21 inhibited glucose uptake and reduced SGLT1 expression in MODE-K cells, which were due to inactivating SGK-1 pathway. Moreover, above effects of FGF-21 on MODE-K cells were abolished by PD173074, a FGFR1 inhibitor. In conclusion, FGF-21 regulates glucose level in diabetes partially due to inhibiting glucose absorption in the SI via inactivating SGK-1 pathway. These results expand our knowledge about how FGF-21 regulates glucose metabolism 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. 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. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Recommanded Product: 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of fibroblasts reduced head and neck cancer growth by targeting fibroblast growth factor receptor was written by Sweeny, Larissa;Liu, Zhiyong;Lancaster, William;Hart, Justin;Hartman, Yolanda E.;Rosenthal, Eben L.. And the article was included in Laryngoscope in 2012.Product Details of 219580-11-7 The following contents are mentioned in the article:

Head and neck squamous cell carcinoma (HNSCC) is a complex disease process involving interactions with carcinoma-associated fibroblasts and endothelial cells. We further investigated these relationships by suppressing stromal cell growth through the inhibition of fibroblast growth factor receptor (FGFR). HNSCC cell lines (FADU, OSC19, Cal27, SCC1, SCC5, SCC22A), fibroblast (HS27), and endothelial cells (human umbilical vascular endothelial cell) were cultured individually or in coculture. Proliferation was assessed following treatment with a range of physiol. concentrations of FGFR inhibitor PD173074. Mice bearing established HNSCC xenografts were treated with PD173074 (12 mg/kg), and tumor histol. was analyzed for stromal composition, proliferation (Ki67 staining), and apoptosis (TUNEL [terminal deoxynucleotidyl transferase dUTP nick end labeling] staining). In vitro, inhibition of FGFR with PD173074 dramatically reduced proliferation of fibroblasts and endothelial cells compared to untreated controls. However, HNSCC cell proliferation was not affected by inhibition of FGFR. When cocultured with fibroblasts, HNSCC cells proliferation increased by 15% to 80% (P < .01). Furthermore, this fibroblast-enhanced tumor cell growth was suppressed by FGFR inhibition. Addnl., treatment of mice bearing HNSCC xenografts with PD173074 resulted in significant growth inhibition (P < .001). Addnl., those tumors from mice treated with PD173074 had a smaller stromal component, decreased proliferation, and increased apoptosis. Targeting the FGFR pathway in head and neck cancer acts through the stromal components to decrease HNSCC growth in vivo and in vitro. 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: 219580-11-7Product Details 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. 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.Product Details of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The over-expression of FGFR4 could influence the features of gastric cancer cells and inhibit the efficacy of PD173074 and 5-fluorouracil towards gastric cancer was written by Li, Jingjing;Ye, Yanwei;Wang, Min;Lu, Lisha;Han, Chao;Zhou, Yubing;Zhang, Jingmin;Yu, Zujiang;Zhang, Xiefu;Zhao, Chunlin;Wen, Jianguo;Kan, Quancheng. And the article was included in Tumor Biology in 2016.COA of Formula: C28H41N7O3 The following contents are mentioned in the article:

The aim was to investigate the function of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the treatment value of agent targeted to FGFR4. Function assays in vitro and in vivo were performed to investigate the discrepancy of biol. features among the GC cells with different expression of FGFR4. GC cells were treated with the single and combination of PD173074 (PD, an inhibitor of FGFR4) and 5-fluorouracil (5-Fu). The invasion ability were stronger, and the apoptosis rates were lower in MGC803 and BGC823 cells treated with FGFR4-LV5 (over-expression of FGFR4 protein) (P < 0.05). The proliferation ability of GC cells is reduced when treated by the single and combination of 5-Fu and PD while that of the FGFR4-LV5 group was less inhibited compared with control group (P < 0.05). The apoptosis rates are remarkably increased in GC cells treated with the single and combination of 5-Fu and PD (P < 0.05). However, the apoptosis rate obviously is reduced in GC cells treated with FGFR4-LV5 compared with control group (P < 0.05). The expression of PCNA and Bcl-XL is remarkably decreased, and the expression of Caspase-3 and cleaved Caspase-3 is obviously increased in GC cells treated with the single and combination of 5-Fu and PD. The tumor volumes of nude mice in FGFR4-LV5 group were much more increased (P < 0.05). The over-expression of FGFR4 enhanced the proliferation ability of GC in vitro and in vivo. The combination of 5-Fu and PD exerted synergetic effect in weakening the proliferation ability and promoting apoptosis in GC cells, while the over-expression of FGFR4 might inhibit the efficacy of two drugs. 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. 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. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.COA of Formula: C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Glycogen Synthase Kinase 3β Promotes the Endocytosis of Transferrin in the African Trypanosome was written by Guyett, Paul J.;Xia, Shuangluo;Swinney, David C.;Pollastri, Michael P.;Mensa-Wilmot, Kojo. And the article was included in ACS Infectious Diseases in 2016.Category: pyrimidines The following contents are mentioned in the article:

Human parasite Trypanosoma brucei proliferates in the blood of its host, where it takes up iron via receptor-mediated endocytosis of transferrin (Tf). Mechanisms of Tf endocytosis in the trypanosome are not fully understood. Small mol. lapatinib inhibits Tf endocytosis in T. brucei and associates with protein kinase GSK3β (TbGSK3β). Therefore, we hypothesized that Tf endocytosis may be regulated by TbGSK3β, and we used three approaches (both genetic and small mol.) to test this possibility. First, the RNAi knock-down of TbGSK3β reduced Tf endocytosis selectively, without affecting the uptake of haptaglobin-Hb (Hp-Hb) or bovine serum albumin (BSA). Second, the overexpression of TbGSK3β increased the Tf uptake. Third, small-mol. inhibitors of TbGSK3β, TWS119 (IC₅₀ = 600 nM), and GW8510 (IC₅₀ = 8 nM) reduced Tf endocytosis. Furthermore, TWS119, but not GW8510, selectively blocked Tf uptake. Thus, TWS119 phenocopies the selective endocytosis effects of a TbGSK3β knockdown. Two new inhibitors of TbGSK3β, LY2784544 (IC₅₀ = 0.6 μM) and sorafenib (IC₅₀ = 1.7 μM), were discovered in a focused screen: at low micromolar concentrations, they prevented Tf endocytosis as well as trypanosome proliferation (GI₅₀‘s were 1.0 and 3.1 μM, resp.). These studies show that (a) TbGSK3β regulates Tf endocytosis, (b) TWS119 is a small-mol. tool for investigating the endocytosis of Tf, (c) endocytosis of GPI-anchored TfR and HpHbR are differentially regulated, and (d) the imidazopyridazine aminopyrazole scaffold of LY2784544 is attractive for a hit-to-lead optimization program in antitrypanosome drug discovery. 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: 219580-11-7Category: pyrimidines).

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. 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

Design, Synthesis and Screening Studies of Potent Thiazol-2-Amine Derivatives as Fibroblast Growth Factor Receptor 1 Inhibitors was written by Suneel Kumar, B. V. S.;Lakshmi, Narasu;Kumar, M. Ravi;Rambabu, Gundla;Manjashetty, Thimmappa H.;Arunasree, Kalle M.;Sriram, Dharmarajan;Ramkumar, Kavya;Neamati, Nouri;Dayam, Raveendra;Sarma, J. A. R. P.. And the article was included in Current Topics in Medicinal Chemistry in 2014.Synthetic Route of C28H41N7O3 The following contents are mentioned in the article:

Fibroblast growth factor receptor 1 (FGFR1) a tyrosine kinase receptor, plays important roles in angiogenesis, embryonic development, cell proliferation, cell differentiation, and wound healing. The FGFR isoforms and their receptors (FGFRs) considered as a potential targets and under intense research to design potential anticancer agents. Fibroblast growth factors (FGF’s) and its growth factor receptors (FGFR) plays vital role in one of the critical pathway in monitoring angiogenesis. In the current study, quant. pharmacophore models were generated and validated using known FGFR1 inhibitors. The pharmacophore models were generated using a set of 28 compounds (training). The top pharmacophore model was selected and validated using a set of 126 compounds (test set) and also using external validation. The validated pharmacophore was considered as a virtual screening query to screen a database of 400,000 virtual mols. and pharmacophore model retrieved 2800 hits. The retrieved hits were subsequently filtered based on the fit value. The selected hits were subjected for docking studies to observe the binding modes of the retrieved hits and also to reduce the false positives. One of the potential hits (thiazole-2-amine derivative) was selected based the pharmacophore fit value, dock score, and synthetic feasibility. A few analogs of the thiazole-2-amine derivative were synthesized. These compounds were screened for FGFR1 activity and anti-proliferative studies. The top active compound showed 56.87% inhibition of FGFR1 activity at 50 μM and also showed good cellular activity. Further optimization of thiazole-2-amine derivatives is in progress. 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: 219580-11-7Synthetic Route 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 also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Synthetic Route of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

PDGFR-β signaling mediates HMGB1 release in mechanically stressed vascular smooth muscle cells was written by Kim, Ji On;Baek, Seung Eun;Jeon, Eun Yeong;Choi, Jong Min;Jang, Eun Jeong;Kim, Chi Dae. And the article was included in PLoS One in 2022.Synthetic Route of C28H41N7O3 The following contents are mentioned in the article:

Mech. stressed vascular smooth muscle cells (VSMCs) have potential roles in the development of vascular complications. However, the underlying mechanisms are unclear. Using VSMCs cultured from rat thoracic aorta explants, we investigated the effects of mech. stretch (MS) on the cellular secretion of high mobility group box 1 (HMGB1), a major damage-associated mol. pattern that mediates vascular complications in stressed vasculature. ELISA (ELISA) demonstrated an increase in the secretion of HMGB1 in VSMCs stimulated with MS (0-3% strain, 60 cycles/min), and this secretion was markedly and time-dependently increased at 3% MS. The increased secretion of HMGB1 at 3% MS was accompanied by an increased cytosolic translocation of nuclear HMGB1; the acetylated and phosphorylated forms of this protein were significantly increased. Among various inhibitors of membrane receptors mediating mech. signals, AG1295 (a platelet-derived growth factor receptor (PDGFR) inhibitor) attenuated MS-induced HMGB1 secretion. Inhibitors of other receptors, including epidermal growth factor, insulin-like growth factor, and fibroblast growth factor receptors, did not inhibit this secretion. Addnl., MS-induced HMGB1 secretion was markedly attenuated in PDGFR-β-deficient cells but not in cells transfected with PDGFR-α siRNA. Likewise, PDGF-DD, but not PDGF-AA, directly increased HMGB1 secretion in VSMCs, indicating a pivotal role of PDGFR-β signaling in the secretion of this protein in VSMCs. Thus, targeting PDGFR-β-mediated secretion of HMGB1 in VSMCs might be a promising therapeutic strategy for vascular complications associated with hypertension. 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: 219580-11-7Synthetic Route 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 nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Synthetic Route of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia