Category: 1062368-24-4

Application of in vitro drug metabolism studies in chemical structure optimization for the treatment of fibrodysplasia ossificans progressiva (FOP) was written by Padilha, Elias C.;Wang, Jianyao;Kerns, Ed;Lee, Arthur;Huang, Wenwei;Jiang, Jian-kang;McKew, John;Abdul Mutlib;Peccinini, Rosangela G.;Yu, Paul B.;Sanderson, Philip;Xu, Xin. And the article was included in Frontiers in Pharmacology in 2019.Electric Literature of C25H22N6 This article mentions the following:

Currently no approved treatment exists for fibrodysplasia ossificans progressiva (FOP) patients, and disease progression results in severe restriction of joint function and premature mortality. LDN-193189 has been demonstrated to be efficacious in a mouse FOP disease model after oral administration. To support species selection for drug safety evaluation and to guide structure optimization for back-up compounds, in-vitro metabolism of LDN-193189 was investigated in liver microsome and cytosol fractions of mouse, rat, dog, rabbit, monkey and human. Metabolism studies included anal. of reactive intermediate formation using glutathione and potassium cyanide (KCN) and anal. of non-P 450 mediated metabolites in cytosol fractions of various species. Metabolite profiles and metabolic soft spots of LDN-193189 were elucidated using LC/UV and mass spectral techniques. The in-vitro metabolism of LDN-193189 was significantly dependent on aldehyde oxidase, with formation of the major NIH-Q55 metabolite. The piperazinyl moiety of LDN-193189 was liable to NADPH-dependent metabolism which generated reactive iminium intermediates, as confirmed through KCN trapping experiments, and aniline metabolites (M337 and M380), which brought up potential drug safety concerns. Subsequently, strategies were employed to avoid metabolic liabilities leading to the synthesis of Quinoline, 2-methyl-4-6-[[4-(1-piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-; 6-({[2-(piperidin-1-yl)ethoxy]pyridin-3-yl}pyrazolo[1,5-a]pyrimidin-3-yl)quinoline and 2-methyl-4-(6-{6-[2-(piperidin-1-yl)ethoxy]pyridin-3-yl}pyrazolo[1,5-a]pyrimidin-3-yl)quinoline. This study demonstrated the importance of metabolite identification for the discovery of novel and safe drug candidates for the treatment of FOP and helped medicinal chemists steer away from potential metabolic liabilities. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Electric Literature of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. 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.Electric Literature of C25H22N6

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

Towards a defined ECM and small molecule based monolayer culture system for the expansion of mouse and human intestinal stem cells was written by Tong, Zhixiang;Martyn, Keir;Yang, Andy;Yin, Xiaolei;Mead, Benjamin E.;Joshi, Nitin;Sherman, Nicholas E.;Langer, Robert S.;Karp, Jeffrey M.. And the article was included in Biomaterials in 2018.Quality Control of 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline This article mentions the following:

Current ISC culture systems face significant challenges such as animal-derived or undefined matrix compositions, batch-to-batch variability (e.g. Matrigel-based organoid culture), and complexity of assaying cell aggregates such as organoids which renders the research and clin. translation of ISCs challenging. Here, through screening for suitable ECM components, we report a defined, collagen based monolayer culture system that supports the growth of mouse and human intestinal epithelial cells (IECs) enriched for an Lgr5⁺ population comparable or higher to the levels found in a standard Matrigel-based organoid culture. The system, referred to as the Bolstering Lgr5 Transformational (BLT) Sandwich culture, comprises a collagen IV-coated porous substrate and a collagen I gel overlay which sandwich an IEC monolayer in between. The distinct collagen cues synergistically regulate IEC attachment, proliferation, and Lgr5 expression through maximizing the engagement of distinct cell surface adhesion receptors (i.e. integrin α2β1, integrin β4) and cell polarity. Further, we apply our BLT Sandwich system to identify that the addition of a bone morphogenetic protein (BMP) receptor inhibitor (LDN-193189) improves the expansion of Lgr5-GFP⁺ cells from mouse small intestinal crypts by nearly 2.5-fold. Notably, the BLT Sandwich culture is capable of expanding human-derived IECs with higher LGR5 mRNA levels than conventional Matrigel culture, providing superior expansion of human LGR5⁺ ISCs. Considering the key roles Lgr5⁺ ISCs play in intestinal epithelial homeostasis and regeneration, we envision that our BLT Sandwich culture system holds great potential for understanding and manipulating ISC biol. in vitro (e.g. for modeling ISC-mediated gut diseases) or for expanding a large number of ISCs for clin. utility (e.g. for stem cell therapy). In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Quality Control of 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Quality Control of 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline

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

SMAD5 signaling: more than meets the nuclei was written by Orlowski, John. And the article was included in Cell Research in 2017.Category: piperazines This article mentions the following:

SMADs are essential transcriptional effectors of transforming growth factor-β (TGFβ)/TGFβ-related signaling that underlies embryonic development and adult homeostasis. A recent study by Fang et al in Cell Research adds to this biol. complexity by demonstrating an atypical cytoplasmic role for SMAD5 in modulating the bioenergetic homeostasis (i.e., glycolysis and mitochondrial respiration) of cells in response to fluctuations in intracellular pH that is independent of receptor signaling. SMAD5 was found to promote not only mitochondrial respiration but also glycolysis in a manner that was influenced by cytoplasmic pH (pHc) and seemingly distinct from the mitochondrial actions of ‘inactive’ cytoplasmic SMAD2. Increases in pHc above 7.2 promoted rapid accumulation of SMAD5 within the cytoplasm, whereas decreases below pHc 7.2 favored its accrual in the nucleus. Further mechanistic studies revealed that pHc-sensing by SMAD5 was conferred by one basic (lysine residues) and two acidic (aspartate and glutamate residues) amino acid clusters in its N-terminal MH1 domain. The pH sensitivity of SMAD5 is intriguing in light of recent reports showing that increases in intracellular pH (pHi) are required for the efficient differentiation of embryonic and adult stem cells. To determine whether there was a functional connection between these seemingly disparate events, the authors performed an elaborate series of experiments that compared the transcriptome profiles of wild-type (WT), SMAD5 knockout (KO) and LDN-193189 (an inhibitor of BMP signaling)-treated human embryonic stem cells (hESCs). The analyses revealed that loss of SMAD5 resulted in the downregulation of a unique subset of genes involved in cellular ion and metabolic homeostasis that were distinct from those affected by blocking BMP signaling. While the mechanism by which cytoplasmic SMAD5 directly stimulates glycolysis is largely resolved, how it regulates mitochondrial morphol. and respiration is less certain. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Category: piperazines).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Category: piperazines

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

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.Recommanded Product: 1062368-24-4 This article mentions the following:

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. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Recommanded Product: 1062368-24-4).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Recommanded Product: 1062368-24-4

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

Modeling glioma with human embryonic stem cell-derived neural lineages was written by Modrek, Aram S.;Prado, Jod;Bready, Devin;Dhaliwal, Joravar;Golub, Danielle;Placantonakis, Dimitris G.. And the article was included in Methods in Molecular Biology (New York, NY, United States) in 2018.Product Details of 1062368-24-4 This article mentions the following:

Gliomas are malignant primary tumors of the central nervous system. Their cell-of-origin is thought to be a neural progenitor or stem cell that acquires mutations leading to oncogenic transformation. Thanks to advances in human stem cell biol., it has become possible to derive human cell types that represent putative cells-of-origin in vitro and model the gliomagenesis process by systematically introducing genetic alterations in these human cells. Here, we present methods to derive human neural stem cells (NSCs) from human embryonic stem cells (hESCs). Because these NSCs are genetically unmodified at baseline, they can be used as a cellular platform to study the effects of individual oncogenic hits in a well-controlled manner in the backdrop of a human genetic background. We also present some key applications of these NSCs, which include their transduction with lentiviral vectors, their neuroglial differentiation and xenografting methods into immunocompromised mice to assess in vivo behavior. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Product Details of 1062368-24-4).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Product Details of 1062368-24-4

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