Tag: 463.5719

In situ imaging of quantum dot-AZD4547 conjugates for tracking the dynamic behavior of fibroblast growth factor receptor 3 was written by Hwang, Gyoyeon;Kim, Hyeonhye;Yoon, Hojong;Song, Chiman;Lim, Dong-Kwon;Sim, Taebo;Lee, Jiyeon. And the article was included in International Journal of Nanomedicine in 2017.HPLC of Formula: 1035270-39-3 This article mentions the following:

Fibroblast growth factor receptors (FGFRs) play an important role in determining cell proliferation, differentiation, migration, and survival. Although a variety of small-mol. FGFR inhibitors have been developed for cancer therapeutics, the interaction between FGFRs and FGFR inhibitors has not been well characterized. The FGFR-inhibitor interaction can be characterized using a new imaging probe that has strong, stable signal properties for in situ cellular imaging of the interaction without quenching. We developed a kinase-inhibitor-modified quantum dot (QD) probe to investigate the interaction between FGFR and potential inhibitors. Especially, turbo-green fluorescent protein-FGFR3s were overexpressed in HeLa cells to investigate the colocalization of FGFR3 and AZD4547 using the QD-AZD4547 probe. The result indicates that this probe is useful for investigating the binding behaviors of FGFR3 with the FGFR inhibitor. Thus, this new inhibitor-modified QD probe is a promising tool for understanding the interaction between FGFR and inhibitors and for creating future high-content, cell-based drug screening strategies. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3HPLC of Formula: 1035270-39-3).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.HPLC of Formula: 1035270-39-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Effects of FGFR inhibitors TKI258, BGJ398 and AZD4547 on breast cancer cells in 2D, 3D and tissue explant cultures was written by Kahkonen, T. E.;Toriseva, M.;Petruk, N.;Virta, A.-R.;Maher, A.;Eigeliene, N.;Kaivola, J.;Bostrom, P.;Koskivuo, I.;Nees, M.;Tuomela, J. M.;Ivaska, K. K.;Harkonen, P. L.. And the article was included in Cellular Oncology in 2021.COA of Formula: C26H33N5O3 This article mentions the following:

Here, we aimed to compare the effects of three FGFR inhibitors (FGFRis), i.e., non-selective TKI258 and selective BGJ398 and AZD4547, on different BC-derived cell lines (BCCs) and primary tissues. Methods: The human BCCs MCF-7 and MDA-MB-231(SA) (wild-type FGFR) and MFM223 (amplified FGFR1 and FGFR2) were analyzed for FGFR expression using qRT-PCR, and the effects of FGFRis on FGFR signaling by Western blotting. Results: We found that all FGFRis tested decreased the growth and viability of BC cells in 2D and 3D cultures. BGJ398 and AZD4547 were found to be potent at low concentrations in FGFR-amplified MFM233 cells, whereas higher concentrations were required in non-amplified MCF7 and MDA-MB-231(SA) cells. TKI258 inhibited the migration and invasion, whereas BGJ398 and AZD4547 only inhibited the invasion of MDA-MB-231(SA) cells. FGFRi treatment of MCF7 and MFM223 cells enhanced the inhibitory effect of radiotherapy, but this effect was not observed in MDA-MB-231(SA) cells. FGFRi-treated primary BC explants with moderate FGFR levels showed a tendency towards decreased proliferation and increased apoptosis. Conclusions: Our results indicate that, besides targeting FGFR-amplified BCs with selective FGFRis, also BCs without FGFR amplification/activation may benefit from FGFRi-treatment. Combination with other treatment modalities, such as radiotherapy, may allow the use of FGFRis at relatively low concentrations and, thereby, contribute to better BC treatment outcomes. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3COA of Formula: C26H33N5O3).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.COA of Formula: C26H33N5O3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

FGF2/FGFR1 regulates autophagy in FGFR1- amplified non-small cell lung cancer cells was written by Yuan, Hong;Li, Zi-Ming;Shao, Jiaxiang;Ji, Wen-Xiang;Xia, Weiliang;Lu, Shun. And the article was included in Journal of Experimental & Clinical Cancer Research in 2017.HPLC of Formula: 1035270-39-3 This article mentions the following:

Autophagy is a conserved catabolic process to degrade cellular organelles. The role of autophagy in cancer development is complex. Amplification of fibroblast growth factor receptor 1 (FGFR1) is one of the most frequent targets in lung squamous cell carcinoma (SQCC). Whether fibroblast growth factor 2 (FGF2)/FGFR1 contributes to the regulation of autophagy remains elusive. Autophagic activity was evaluated by immunoblotting for microtubule-associated protein 1 light chain 3 (LC3), formation of GFP-LC3 puncta, and monodansylcadaverine (MDC) staining. The effect of autophagy inhibition on cell survival was assessed by cell viability and apoptosis assays. We elucidated that FGFR1 activation suppressed autophagy. Pharmacol. or genetic inhibition of FGFR1 by AZD4547 or FGFR1 short hairpin RNA (shRNA) induced autophagy in FGFR1-amplified non-small-cell lung cancer (NSCLC) cells, H1581 and H520 cells. Mechanistic study revealed that the induction of autophagy by FGFR1 inhibition was mediated through inhibiting the ERK/MAPK pathway not by AKT pathway, accompanied by upregulation of beclin-1. Furthermore, activation of ERK/MAPK by transfection with a constitutively active MEK1 (caMEK1) construct or knockdown of beclin-1 by RNAi could attenuate autophagy induced by FGFR1 inhibition. Beclin-1 expression was inversely correlated with MEK1 phosphorylation. Inhibition of autophagy by beclin-1 silencing could enhance apoptosis after AZD4547 treatment in H1581 and H520 cells. High levels of LC3B mRNA was a marker of poor prognosis in NSCLC patients. Simultaneously inhibiting FGFR1 and autophagy could enhance cell death which should be further explored in vivo. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3HPLC of Formula: 1035270-39-3).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).HPLC of Formula: 1035270-39-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

In vivo effects of AZD4547, a novel fibroblast growth factor receptor inhibitor, in a mouse model of endometriosis was written by Santorelli, Sara;Fischer, Deborah P.;Harte, Michael K.;Laru, Johanna;Marshall, Kay M.. And the article was included in Pharmacology Research & Perspectives in 2021.SDS of cas: 1035270-39-3 This article mentions the following:

Endometriosis is a chronic disease, characterized by the growth of endometrial-like cells outside the uterine cavity. Due to its complex pathophysiol., a totally resolving cure is yet to be found. The aim of this study was to compare the therapeutic efficacy of AZD4547, a novel fibroblast growth factor receptor inhibitor (FGFRI), with a well-characterized progestin, etonogestrel (ENG) using a validated in vivo mouse model of endometriosis. Endometriosis was induced by transplanting uterine fragments from donor mice in proestrus into the peritoneal cavity of recipient mice, which then developed into cyst-like lesions. AZD4547 and ENG were administered systemically either from the day of endometriosis induction or 2-wk post-surgery. After 20 days of treatment, the lesions were harvested; their size and weight were measured and analyzed histol. or by qRT-PCR. Stage of estrous cycle was monitored throughout. Compared to vehicle, AZD4547 (25 mg/kg) was most effective in counteracting lesion growth when treating from day of surgery and 2 wk after; ENG (0.8 mg/kg) was similarly effective in reducing lesion growth but only when administered from day of surgery. Each downregulated FGFR gene expression (p < 0.05). AZD4547 at all doses and ENG (0.008 mg/kg) caused no disturbance to the estrous cycle. ENG at 0.08 and 0.8 mg/kg was associated with partial or complete estrous cycle disruption and hyperemia of the uteri. AZD4547 and ENG both attenuated endometriotic lesion size, but only AZD4547 did not disrupt the estrous cycle, suggesting that targeting of FGFR is worthy of further investigation as a novel treatment for endometriosis. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3SDS of cas: 1035270-39-3).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.SDS of cas: 1035270-39-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Revealing the Unbinding Kinetics and Mechanism of Type I and Type II Protein Kinase Inhibitors by Local-Scaled Molecular Dynamics Simulations was written by Du, Yu;Wang, Renxiao. And the article was included in Journal of Chemical Theory and Computation in 2020.COA of Formula: C26H33N5O3 This article mentions the following:

Protein kinase inhibitors disrupt phosphorylation of the target kinases, which are an important class of drug for treating cancer and other diseases. Conventional structure-based design methods (such as mol. docking) focus on the static binding mode of the kinase inhibitor with its target. However, dissociation kinetic properties of a drug mol. are found to correlate with its residence time in vivo and thus have drawn the attention of drug designers in recent years. In this study, we have applied the local-scaled mol. dynamics (MD) simulation enabled in GROMACS software to explore the unbinding mechanism of a total of 41 type I and type II kinase inhibitors. Our simulation considered multiple starting configurations as well as possible protonation states of kinase inhibitors. Based on our local-scaled MD results, we discovered that the integrals of the favorable binding energy during dissociation correlated well (R² = 0.64) with the exptl. dissociation rate constants of those kinase inhibitors on the entire data set. Given its accuracy and tech. advantage, this method may serve as a practical option for estimating this important property in reality. Our simulation also provided a reasonable explanation of the dynamic properties of kinase and its inhibitor as well as the role of relevant water mols. in dissociation In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3COA of Formula: C26H33N5O3).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.COA of Formula: C26H33N5O3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

miR-217-5p regulates myogenesis in skeletal muscle stem cells by targeting FGFR2 was written by Zhu, Menghai;Chen, Gang;Yang, Yi;Yang, Jiantao;Qin, Bengang;Gu, Liqiang. And the article was included in Molecular Medicine Reports in 2020.Quality Control of rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide This article mentions the following:

MicroRNA-217-5p (miR-217-5p) has been implicated in cell proliferation; however, its role in skeletal muscle stem cells (SkMSCs) remains unknown. The present study aimed to explore the roles of miR-217-5p in the biol. characteristics of SkMSCs. SkMSCs were identified by cell surface markers using flow cytometry. The present study observed that miR-217-5p mimics accelerated the proliferation and suppressed the differentiation in SkMSCs. In addition, the results of the present study revealed that fibroblast growth factor receptor 2 (FGFR2) was a target of miR-217-5p, as miR-217-5p bound directly to the 3′-untranslated region of FGFR2 mRNA, resulting in increased FGFR2 mRNA and protein levels. In addition, the present study suppressed the expression of FGFR2 in SkMSCs using a selective FGFR inhibitor AZD4547 and detected the efficiency of inhibition by reverse transcription-quant. PCR and western blotting. miR-217-5p levels were pos. associated with FGFR2 expression, which was upregulated and accelerated the proliferation of SkMSCs compared with that of the miR-NC group. MiR-217-5p levels were pos. associated with FGFR2 expression, which was upregulated and accelerated the proliferation of SkMSCs compared with that of the miR-NC group. Collectively, these results demonstrated that miR-217-5p may act as a myogenesis promoter in SkMSCs by directly targeting FGFR2 and may regulate the myogenesis of these cells. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3Quality Control of rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Quality Control of rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Phenotypic Screening Combined with Machine Learning for Efficient Identification of Breast Cancer-Selective Therapeutic Targets was written by Gautam, Prson;Jaiswal, Alok;Aittokallio, Tero;Al-Ali, Hassan;Wennerberg, Krister. And the article was included in Cell Chemical Biology in 2019.Name: rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide This article mentions the following:

The lack of functional understanding of most mutations in cancer, combined with the non-druggability of most proteins, challenge genomics-based identification of oncol. drug targets. We implemented a machine-learning-based approach (idTRAX), which relates cell-based screening of small-mol. compounds to their kinase inhibition data, to directly identify effective and readily druggable targets. We applied idTRAX to triple-neg. breast cancer cell lines and efficiently identified cancer-selective targets. For example, we found that inhibiting AKT selectively kills MFM-223 and CAL148 cells, while inhibiting FGFR2 only kills MFM-223. Since the effects of catalytically inhibiting a protein can diverge from those of reducing its levels, targets identified by idTRAX frequently differ from those identified through gene knockout/knockdown methods. This is critical if the purpose is to identify targets specifically for small-mol. drug development, whereby idTRAX may produce fewer false-positives. The rapid nature of the approach suggests that it may be applicable in personalizing therapy. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3Name: rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Name: rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics