Tag: 404.4435

Chemical genetics screen identifies epigenetic mechanisms involved in dopaminergic and noradrenergic neurogenesis in zebrafish was written by Westphal, Markus;Sant, Pooja;Hauser, Alexander-Thomas;Jung, Manfred;Driever, Wolfgang. And the article was included in Frontiers in Genetics in 2020.Electric Literature of C17H20N6O4S This article mentions the following:

The cell type diversity and complexity of the nervous system is generated by a network of signaling events, transcription factors, and epigenetic regulators. Signaling and transcriptional control have been easily amenable to forward genetic screens in model organisms like zebrafish. In contrast, epigenetic mechanisms have been somewhat elusive in genetic screens, likely caused by broad action in multiple developmental pathways that masks specific phenotypes, but also by genetic redundancies of epigenetic factors. Here, we performed a screen using small mol. inhibitors of epigenetic mechanisms to reveal contributions to specific aspects of neurogenesis in zebrafish. We chose development of dopaminergic and noradrenergic neurons from neural progenitors as target of epigenetic regulation. First, we tested a small mol. inhibitor library that targets a broad range of epigenetic protein classes and mechanisms, using expression of the dopaminergic and noradrenergic marker tyrosine hydroxylase as readout. We analyzed treated embryos for effects on neural stem cells, growth progression of the retina, and apoptosis in neural tissues. In addition, we analyzed effects on islet1 expressing neuronal populations to determine potential selectivity of compounds for transmitter phenotypes. In summary, our targeted screen of epigenetic inhibitors identified specific compounds, which reveal chromatin regulator classes that contribute to dopaminergic and noradrenergic neurogenesis in vivo. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Electric Literature of C17H20N6O4S).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Pyridazine compounds have attracted interest in various fields like medicinal, industrial, and agricultural research as they are used for numerous biological activities and other applications.Electric Literature of C17H20N6O4S

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Epigenetic drug screen identifies the histone deacetylase inhibitor NSC3852 as a potential novel drug for the treatment of pediatric acute myeloid leukemia was written by Wiggers, Caroline R. M.;Govers, Anita M. A. P.;Lelieveld, Daphne;Egan, David A.;Zwaan, C. Michel;Sonneveld, Edwin;Coffer, Paul J.;Bartels, Marije. And the article was included in Pediatric Blood & Cancer in 2019.Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate This article mentions the following:

Acute myeloid leukemia (AML) is a heterogeneous disease regarding morphol., immunophenotyping, genetic abnormalities, and clin. behavior. The overall survival rate of pediatric AML is 60% to 70%, and has not significantly improved over the past two decades. Children with Down syndrome (DS) are at risk of developing acute megakaryoblastic leukemia (AMKL), which can be preceded by a transient myeloproliferative disorder during the neonatal period. Intensification of current treatment protocols is not feasible due to already high treatment-related morbidity and mortality. Instead, more targeted therapies with less severe side effects are highly needed. To identify potential novel therapeutic targets for myeloid disorders in children, including DS-AMKL and non-DS-AML, we performed an unbiased compound screen of 80 small mols. targeting epigenetic regulators in three pediatric AML cell lines that are representative for different subtypes of pediatric AML. Three candidate compounds were validated and further evaluated in normal myeloid precursor cells during neutrophil differentiation and in (pre-)leukemic pediatric patient cells. Candidate drugs LMK235, NSC3852, and bromosporine were effective in all tested pediatric AML cell lines with antiproliferative, proapoptotic, and differentiation effects. Out of these three compounds, the pan-histone deacetylase inhibitor NSC3852 specifically induced growth arrest and apoptosis in pediatric AML cells, without disrupting normal neutrophil differentiation. NSC3852 is a potential candidate drug for further preclin. testing in pediatric AML and DS-AMKL. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Pyridazine is bioavailable (especially in the CNS) and can reduce toxicity. Pyridazine is a component of several drug molecules, and the pyridazine pharmacophore has contributed to a variety of pharmacologically active compounds.Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia was written by Picaud, Sarah;Leonards, Katharina;Lambert, Jean-Philippe;Dovey, Oliver;Wells, Christopher;Fedorov, Oleg;Monteiro, Octovia;Fujisawa, Takao;Wang, Chen-Yi;Lingard, Hannah;Tallant, Cynthia;Nikbin, Nikzad;Guetzoyan, Lucie;Ingham, Richard;Ley, Steven V.;Brennan, Paul;Muller, Susanne;Samsonova, Anastasia;Gingras, Anne-Claude;Schwaller, Juerg;Vassiliou, George;Knapp, Stefan;Filippakopoulos, Panagis. And the article was included in Science Advances in 2016.Recommanded Product: 1619994-69-2 This article mentions the following:

Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo and extra-terminal) inhibitors and their significant activity in diverse tumor models have rapidly translated into clin. studies and have motivated drug development efforts targeting non-BET BRDs. However, the complexmultidomain/subunit architecture of BRD protein complexes complicates predictions of the consequences of their pharmacol. targeting. To address this issue, we developed a promiscuous BRD inhibitor [bromosporine (BSP)] that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle, we studied the effects of BSP on leukemic cell lines known to be sensitive to BET inhibition and found, as expected, strong antiproliferative activity. Comparison of the modulation of transcriptional profiles by BSP after a short exposure to the inhibitor resulted in a BET inhibitor signature but no significant addnl. changes in transcription that could account for inhibition of other BRDs. Thus, nonselective targeting of BRDs identified BETs, but not other BRDs, as master regulators of contextdependent primary transcription response. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Recommanded Product: 1619994-69-2).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. Pyridazine and derivatives coordinate readily with transition metals to form complexes and catalysts with synthetic utility.Recommanded Product: 1619994-69-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

New inhibitors for the BPTF bromodomain enabled by structural biology and biophysical assay development was written by Ycas, Peter D.;Zahid, Huda;Chan, Alice;Olson, Noelle M.;Johnson, Jorden A.;Talluri, Siva K.;Schonbrunn, Ernst;Pomerantz, William C. K.. And the article was included in Organic & Biomolecular Chemistry in 2020.Product Details of 1619994-69-2 This article mentions the following:

Bromodomain-containing proteins regulate transcription through protein-protein interactions with chromatin and serve as scaffolding proteins for recruiting essential members of the transcriptional machinery. One such protein is the bromodomain and PHD-containing transcription factor (BPTF), the largest member of the nucleosome remodeling complex, NURF. Despite an emerging role for BPTF in regulating a diverse set of cancers, small mol. development for inhibiting the BPTF bromodomain has been lacking. Here we cross-validate three complementary biophys. assays to further the discovery of BPTF bromodomain inhibitors for chem. probe development: two direct binding assays (protein-observed ¹⁹F (PrOF) NMR and surface plasmon resonance (SPR)) and a competitive inhibition assay (AlphaScreen). We first compare the assays using three small mols. and acetylated histone peptides with reported affinity for the BPTF bromodomain. Using SPR with both unlabeled and fluorinated BPTF, we further determine that there is a minimal effect of ¹⁹F incorporation on ligand binding for future PrOF NMR experiments To guide medicinal chem. efforts towards chem. probe development, we subsequently evaluate two new BPTF inhibitor scaffolds with our suite of biophys. assays and rank-order compound affinities which could not otherwise be determined by PrOF NMR. Finally, we cocrystallize a subset of small mol. inhibitors and present the first published small mol.-protein structures with the BPTF bromodomain. We envision the biophys. assays described here and the structural insights from the crystallog. will guide researchers towards developing selective and potent BPTF bromodomain inhibitors. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Product Details of 1619994-69-2).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Product Details of 1619994-69-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Chemical genetics screen identifies epigenetic mechanisms involved in dopaminergic and noradrenergic neurogenesis in zebrafish was written by Westphal, Markus;Sant, Pooja;Hauser, Alexander-Thomas;Jung, Manfred;Driever, Wolfgang. And the article was included in Frontiers in Genetics in 2020.Electric Literature of C17H20N6O4S This article mentions the following:

The cell type diversity and complexity of the nervous system is generated by a network of signaling events, transcription factors, and epigenetic regulators. Signaling and transcriptional control have been easily amenable to forward genetic screens in model organisms like zebrafish. In contrast, epigenetic mechanisms have been somewhat elusive in genetic screens, likely caused by broad action in multiple developmental pathways that masks specific phenotypes, but also by genetic redundancies of epigenetic factors. Here, we performed a screen using small mol. inhibitors of epigenetic mechanisms to reveal contributions to specific aspects of neurogenesis in zebrafish. We chose development of dopaminergic and noradrenergic neurons from neural progenitors as target of epigenetic regulation. First, we tested a small mol. inhibitor library that targets a broad range of epigenetic protein classes and mechanisms, using expression of the dopaminergic and noradrenergic marker tyrosine hydroxylase as readout. We analyzed treated embryos for effects on neural stem cells, growth progression of the retina, and apoptosis in neural tissues. In addition, we analyzed effects on islet1 expressing neuronal populations to determine potential selectivity of compounds for transmitter phenotypes. In summary, our targeted screen of epigenetic inhibitors identified specific compounds, which reveal chromatin regulator classes that contribute to dopaminergic and noradrenergic neurogenesis in vivo. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Electric Literature of C17H20N6O4S).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Pyridazine compounds have attracted interest in various fields like medicinal, industrial, and agricultural research as they are used for numerous biological activities and other applications.Electric Literature of C17H20N6O4S

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Epigenetic drug screen identifies the histone deacetylase inhibitor NSC3852 as a potential novel drug for the treatment of pediatric acute myeloid leukemia was written by Wiggers, Caroline R. M.;Govers, Anita M. A. P.;Lelieveld, Daphne;Egan, David A.;Zwaan, C. Michel;Sonneveld, Edwin;Coffer, Paul J.;Bartels, Marije. And the article was included in Pediatric Blood & Cancer in 2019.Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate This article mentions the following:

Acute myeloid leukemia (AML) is a heterogeneous disease regarding morphol., immunophenotyping, genetic abnormalities, and clin. behavior. The overall survival rate of pediatric AML is 60% to 70%, and has not significantly improved over the past two decades. Children with Down syndrome (DS) are at risk of developing acute megakaryoblastic leukemia (AMKL), which can be preceded by a transient myeloproliferative disorder during the neonatal period. Intensification of current treatment protocols is not feasible due to already high treatment-related morbidity and mortality. Instead, more targeted therapies with less severe side effects are highly needed. To identify potential novel therapeutic targets for myeloid disorders in children, including DS-AMKL and non-DS-AML, we performed an unbiased compound screen of 80 small mols. targeting epigenetic regulators in three pediatric AML cell lines that are representative for different subtypes of pediatric AML. Three candidate compounds were validated and further evaluated in normal myeloid precursor cells during neutrophil differentiation and in (pre-)leukemic pediatric patient cells. Candidate drugs LMK235, NSC3852, and bromosporine were effective in all tested pediatric AML cell lines with antiproliferative, proapoptotic, and differentiation effects. Out of these three compounds, the pan-histone deacetylase inhibitor NSC3852 specifically induced growth arrest and apoptosis in pediatric AML cells, without disrupting normal neutrophil differentiation. NSC3852 is a potential candidate drug for further preclin. testing in pediatric AML and DS-AMKL. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Pyridazine is bioavailable (especially in the CNS) and can reduce toxicity. Pyridazine is a component of several drug molecules, and the pyridazine pharmacophore has contributed to a variety of pharmacologically active compounds.Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia was written by Picaud, Sarah;Leonards, Katharina;Lambert, Jean-Philippe;Dovey, Oliver;Wells, Christopher;Fedorov, Oleg;Monteiro, Octovia;Fujisawa, Takao;Wang, Chen-Yi;Lingard, Hannah;Tallant, Cynthia;Nikbin, Nikzad;Guetzoyan, Lucie;Ingham, Richard;Ley, Steven V.;Brennan, Paul;Muller, Susanne;Samsonova, Anastasia;Gingras, Anne-Claude;Schwaller, Juerg;Vassiliou, George;Knapp, Stefan;Filippakopoulos, Panagis. And the article was included in Science Advances in 2016.Recommanded Product: 1619994-69-2 This article mentions the following:

Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo and extra-terminal) inhibitors and their significant activity in diverse tumor models have rapidly translated into clin. studies and have motivated drug development efforts targeting non-BET BRDs. However, the complexmultidomain/subunit architecture of BRD protein complexes complicates predictions of the consequences of their pharmacol. targeting. To address this issue, we developed a promiscuous BRD inhibitor [bromosporine (BSP)] that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle, we studied the effects of BSP on leukemic cell lines known to be sensitive to BET inhibition and found, as expected, strong antiproliferative activity. Comparison of the modulation of transcriptional profiles by BSP after a short exposure to the inhibitor resulted in a BET inhibitor signature but no significant addnl. changes in transcription that could account for inhibition of other BRDs. Thus, nonselective targeting of BRDs identified BETs, but not other BRDs, as master regulators of contextdependent primary transcription response. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Recommanded Product: 1619994-69-2).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. Pyridazine and derivatives coordinate readily with transition metals to form complexes and catalysts with synthetic utility.Recommanded Product: 1619994-69-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

New inhibitors for the BPTF bromodomain enabled by structural biology and biophysical assay development was written by Ycas, Peter D.;Zahid, Huda;Chan, Alice;Olson, Noelle M.;Johnson, Jorden A.;Talluri, Siva K.;Schonbrunn, Ernst;Pomerantz, William C. K.. And the article was included in Organic & Biomolecular Chemistry in 2020.Product Details of 1619994-69-2 This article mentions the following:

Bromodomain-containing proteins regulate transcription through protein-protein interactions with chromatin and serve as scaffolding proteins for recruiting essential members of the transcriptional machinery. One such protein is the bromodomain and PHD-containing transcription factor (BPTF), the largest member of the nucleosome remodeling complex, NURF. Despite an emerging role for BPTF in regulating a diverse set of cancers, small mol. development for inhibiting the BPTF bromodomain has been lacking. Here we cross-validate three complementary biophys. assays to further the discovery of BPTF bromodomain inhibitors for chem. probe development: two direct binding assays (protein-observed ¹⁹F (PrOF) NMR and surface plasmon resonance (SPR)) and a competitive inhibition assay (AlphaScreen). We first compare the assays using three small mols. and acetylated histone peptides with reported affinity for the BPTF bromodomain. Using SPR with both unlabeled and fluorinated BPTF, we further determine that there is a minimal effect of ¹⁹F incorporation on ligand binding for future PrOF NMR experiments To guide medicinal chem. efforts towards chem. probe development, we subsequently evaluate two new BPTF inhibitor scaffolds with our suite of biophys. assays and rank-order compound affinities which could not otherwise be determined by PrOF NMR. Finally, we cocrystallize a subset of small mol. inhibitors and present the first published small mol.-protein structures with the BPTF bromodomain. We envision the biophys. assays described here and the structural insights from the crystallog. will guide researchers towards developing selective and potent BPTF bromodomain inhibitors. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Product Details of 1619994-69-2).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Product Details of 1619994-69-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem