371.2168 | - Indole Building Blocks

Bonnet, Raphael et al. published their research in PLoS One in 2022 | CAS: 280744-09-4

3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Recommanded Product: 280744-09-4

Identification of potentially anti-COVID-19 active drugs using the connectivity MAP was written by Bonnet, Raphael;Mariault, Lee;Peyron, Jean-Francois. And the article was included in PLoS One in 2022.Recommanded Product: 280744-09-4 This article mentions the following:

Drug repurposing can be an interesting strategy for an emergency response to the severe acute respiratory syndrome-coronavirus-2, (SARS-COV-2), the causing agent of the coronavirus disease-19 (COVID-19) pandemic. For this, we applied the Connectivity Map (CMap) bioinformatic resource to identify drugs that generate, in the CMap database, gene expression profiles (GEP) that neg. correlate with a SARS-COV-2 GEP, anticipating that these drugs could antagonize the deleterious effects of the virus at cell, tissue or organism levels. We identified several anti-cancer compounds that target MDM2 in the p53 pathway or signaling proteins: Ras, PKB尾, Nitric Oxide synthase, Rho kinase, all involved in the transmission of proliferative and growth signals. We hypothesized that these drugs could interfere with the high rate of biomass synthesis in infected cells, a feature shared with cancer cells. Other compounds including etomoxir, triacsin-c, PTB1-IN-3, are known to modulate lipid metabolism or to favor catabolic reactions by activating AMPK. Four different anti-inflammatory mols., including dexamethasone, fluorometholone and cytosporone-b, targeting the glucocorticoid receptor, cyclooxygenase, or NUR77 also came out of the anal. These results represent a first step in the characterization of potential repositioning strategies to treat SARS-COV-2. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4Recommanded Product: 280744-09-4).

Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Yoshida, Ayaka et al. published their research in Experimental Dermatology in 2021 | CAS: 280744-09-4

Sunitinib decreases the expression of KRT6A and SERPINB1 in 3D human epidermal models was written by Yoshida, Ayaka;Yamamoto, Kazuhiro;Ishida, Takahiro;Omura, Tomohiro;Itoh, Tomoo;Nishigori, Chikako;Sakane, Toshiyasu;Yano, Ikuko. And the article was included in Experimental Dermatology in 2021.Safety of 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione This article mentions the following:

Hand-foot skin reaction (HFSR) is a common side effect caused by several tyrosine kinase inhibitors, including sunitinib. However, the nature of the cornifying factors related to the mol. biol. mechanisms underlying HFSR remains poorly understood. We used human keratinocyte models to investigate the key cornifying factors for dermatol. and biol. abnormalities induced by sunitinib. On the basis of the results of microarray anal. using the three-dimensional (3D) human epidermal model, keratin (KRT)6A, serine protease inhibitor (SERPIN)B1, KRT5, and SERPIN Kazal-type 6 were selected as candidate genes related to HFSR. Sunitinib treatment significantly decreased the expression of SERPINB1 and KRT6A in the immunohistochem. staining of the 3D epidermal model. In PSVK1 cells, but not in normal human epidermal keratinocyte cells, both of which are human normal keratinocyte cell lines, sunitinib decreased the expression of KRT6A with a concomitant decrease in levels of phosphorylated extracellular signal-regulated kinases (ERK)1/2 and phosphorylated p38 mitogen-activated protein kinase (MAPK). Inhibitors of the ERK and p38 MAPK signal pathways also significantly decreased KRT6A expression. Sunitinib-induced decrease in KRT6A expression was suppressed by the inhibition of glycogen synthase kinase-3尾 by enhancing ERK1/2 and p38 MAPK phosphorylation. Thus, sunitinib reduces the expression of KRT6A and SERPINB1 by inhibiting the ERK1/2 and p38 MAPK signalling pathways in the skin model. These changes in expression contribute to the pathol. of HFSR. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4Safety of 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione).

Ding, Mei et al. published their research in ACS Chemical Biology in 2019 | CAS: 280744-09-4

3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4) belongs to indole derivatives. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). COA of Formula: C19H12Cl2N2O2

A phenotypic screening approach using human Treg cells identified regulators of Forkhead Box p3 expression was written by Ding, Mei;Brengdahl, Johan;Lindqvist, Madelene;Gehrmann, Ulf;Ericson, Elke;von Berg, Stefan;Ripa, Lena;Malhotra, Rajneesh. And the article was included in ACS Chemical Biology in 2019.COA of Formula: C19H12Cl2N2O2 This article mentions the following:

Regulatory T (Treg) cells, expressing the transcription factor forkhead box p3 (FOXP3), are the key cells regulating peripheral autoreactive T lymphocytes by suppressing effector T cells. FOXP3⁺ Treg cells play essential roles controlling immune responses in autoimmune diseases and cancer. Several clin. approaches (e.g., polyclonal expansion of Treg cells with anti-CD3 and anti-CD28 coated beads in the presence of drugs) are under evaluation. However, expression of FOXP3, recognized as the master regulator of Treg cells, in induced Treg cells have been shown to be instable, and mol. targets involved in regulating FOXP3 expression and Treg cell function have not been well-defined. Thus, new targets directly regulating FOXP3 expression and the expression of its downstream genes (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA4)) have the potential to stabilize the Treg cell phenotype and function. This report describes the development of an automated medium-throughput 384-well plate flow cytometry phenotypic assay measuring the protein expression of FOXP3 and CTLA4 in human Treg cells. Screening a library of 4213 structurally diverse compounds allowed us to identify a variety of compounds regulating FOXP3 and CTLA4 expression. Further evaluation of these and related small mols., followed by confirmation using siRNA-mediated gene knockdown, revealed three targets: euchromatic histone-lysine N-methyltransferase (EHMT2) and glycogen synthase kinase 3 alpha/beta (GSK3伪/尾) as potent pos. regulators of FOXP3 expression, and bromodomain and extra-terminal domain (BET) inhibitors as neg. regulators of FOXP3 and CTLA4 expression. These targets have potential implications for establishing novel therapies for autoimmune diseases and cancer. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4COA of Formula: C19H12Cl2N2O2).

Yuan, Jifang et al. published their research in Biomaterials Science in 2020 | CAS: 280744-09-4

Sustained release of inhibitor from bionic scaffolds for wound healing and functional regeneration was written by Yuan, Jifang;Hou, Qian;Zhong, Lingzhi;Dai, Xin;Lu, Qiang;Li, Meirong;Fu, Xiaobing. And the article was included in Biomaterials Science in 2020.HPLC of Formula: 280744-09-4 This article mentions the following:

Small mols. play remarkable roles in promoting tissue regeneration, but are limited by their burst release. Various bioactive mols. are required to create a suitable niche for better skin regeneration by controlling their release behaviors. Herein, a small mol. SB216763, a GSK-3 inhibitor, was loaded on silk fibroin nanofibers (SNF), and then mixed with chitosan (CS) to prepare the small mol.-loaded composite bionic scaffolds (CSNF-SB). Given the interaction of SNF and SB216763, the sustained release of SB216763 for more than 21 days was achieved for SNF and CSNF-SB composite scaffolds. Compared to drug-free CSNF scaffolds, CSNF-SB showed better cell adhesion and proliferation capacity, suggesting bioactivity. The upregulated expression of 尾-catenin in fibroblasts in vitro revealed that the released small mols. maintained their function in composite scaffolds. Quicker and better wound healing was realized with the drug-loaded scaffolds, which was significantly superior to that treated with drug-free scaffolds. Unlike the DFO-loaded silk hydrogel system, hair follicle neogenesis was also found in the drug-loaded-scaffold treatment wounds, demonstrating functional recovery. Therefore, silk nanofibers as versatile carriers for different small bioactive mols. could be used to fabricate scaffolds with optimized niches and then achieve functional recovery of tissues. The small mol.-loaded bionic scaffolds have a promising future in skin tissue regeneration. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4HPLC of Formula: 280744-09-4).

Tong, Jingshan et al. published their research in Molecular Cancer Therapeutics in 2017 | CAS: 280744-09-4

3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Recommanded Product: 280744-09-4

Fbw7-dependent mcl-1 degradation mediates the anticancer effect of hsp90 inhibitors was written by Tong, Jingshan;Tan, Shuai;Nikolovska-Coleska, Zaneta;Yu, Jian;Zou, Fangdong;Zhang, Lin. And the article was included in Molecular Cancer Therapeutics in 2017.Recommanded Product: 280744-09-4 This article mentions the following:

Heat shock protein 90 (Hsp90) is widely overexpressed in cancer cells and necessary for maintenance of malignant phenotypes. Hsp90 inhibition induces tumor cell death through degradation of its client oncoproteins and has shown promises in preclin. studies. However, the mechanism by which Hsp90 inhibitors kill tumor cells is not well-understood. Biomarkers associated with differential sensitivity and resistance to Hsp90 inhibitors remain to be identified. In this study, we found that colorectal cancer cells containing inactivating mutations of FBW7, a tumor suppressor and E3 ubiquitin ligase, are intrinsically insensitive to Hsp90 inhibitors. The insensitive colorectal cancer cells lack degradation of Mcl-1, a prosurvival Bcl-2 family protein. Hsp90 inhibition promotes GSK3尾-dependent phosphorylation of Mcl-1, which subsequently binds to FBW7 and undergoes ubiquitination and proteasomal degradation Specifically blocking Mcl-1 phosphorylation by genetic knock-in abrogates its degradation and renders in vitro and in vivo resistance to Hsp90 inhibitors, which can be overcame by Mcl-1-selective small-mol. inhibitors. Collectively, our findings demonstrate a key role of GSK3尾/FBW7-dependent Mcl-1 degradation in killing of colorectal cancer cells by Hsp90 inhibitors and suggest FBW7 mutational status as a biomarker for Hsp90-targeted therapy. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4Recommanded Product: 280744-09-4).

Gaitantzi, Haristi et al. published their research in Cell Death & Disease in 2018 | CAS: 280744-09-4

3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter. It is used in perfumery and in making tryptophan, an essential amino acid, and indoleacetic acid (heteroauxin), a hormone that promotes the development of roots in plant cuttings.Synthetic Route of C19H12Cl2N2O2

Ethanol sensitizes hepatocytes for TGF-尾-triggered apoptosis was written by Gaitantzi, Haristi;Meyer, Christoph;Rakoczy, Pia;Thomas, Maria;Wahl, Kristin;Wandrer, Franziska;Bantel, Heike;Alborzinia, Hamed;Woelfl, Stefan;Ehnert, Sabrina;Nuessler, Andreas;Bergheim, Ina;Ciuclan, Loredana;Ebert, Matthias;Breitkopf-Heinlein, Katja;Dooley, Steven. And the article was included in Cell Death & Disease in 2018.Synthetic Route of C19H12Cl2N2O2 This article mentions the following:

Alc. abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-尾-a potent pro-fibrogenic cytokine-leads to disease progression. Our aim was to elucidate the crosstalk of TGF-尾 and alc. on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-尾 and cell fate was determined Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels. To substantiate findings, animal model specimens and human liver tissue cultures were investigated. On its own, ethanol had no effect on hepatocyte apoptosis, whereas TGF-尾 increased cell death. Combined treatment led to massive hepatocyte apoptosis, which could also be recapitulated in human HCC liver tissue treated ex vivo. Alc. boosted the TGF-尾 pro-apoptotic gene signature. The underlying mechanism of pathway crosstalk involves SMAD and non-SMAD/AKT signaling. Blunting CYP2E1 and ADH activities did not prevent this effect, implying that it was not a consequence of alc. metabolism In line with this, the ethanol metabolite acetaldehyde did not mimic the effect and glutathione supplementation did not prevent the super-induction of cell death. In contrast, blocking GSK-3尾 activity, a downstream mediator of AKT signaling, rescued the strong apoptotic response triggered by ethanol and TGF-尾. This study provides novel information on the crosstalk between ethanol and TGF-尾. We give evidence that ethanol directly leads to a boost of TGF-尾’s pro-apoptotic function in hepatocytes, which may have implications for patients with chronic alc. liver disease. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4Synthetic Route of C19H12Cl2N2O2).

Yoshida, Ayaka et al. published their research in Experimental Dermatology in 2021 | CAS: 280744-09-4

Hand-foot skin reaction (HFSR) is a common side effect caused by several tyrosine kinase inhibitors, including sunitinib. However, the nature of the cornifying factors related to the mol. biol. mechanisms underlying HFSR remains poorly understood. We used human keratinocyte models to investigate the key cornifying factors for dermatol. and biol. abnormalities induced by sunitinib. On the basis of the results of microarray anal. using the three-dimensional (3D) human epidermal model, keratin (KRT)6A, serine protease inhibitor (SERPIN)B1, KRT5, and SERPIN Kazal-type 6 were selected as candidate genes related to HFSR. Sunitinib treatment significantly decreased the expression of SERPINB1 and KRT6A in the immunohistochem. staining of the 3D epidermal model. In PSVK1 cells, but not in normal human epidermal keratinocyte cells, both of which are human normal keratinocyte cell lines, sunitinib decreased the expression of KRT6A with a concomitant decrease in levels of phosphorylated extracellular signal-regulated kinases (ERK)1/2 and phosphorylated p38 mitogen-activated protein kinase (MAPK). Inhibitors of the ERK and p38 MAPK signal pathways also significantly decreased KRT6A expression. Sunitinib-induced decrease in KRT6A expression was suppressed by the inhibition of glycogen synthase kinase-3β by enhancing ERK1/2 and p38 MAPK phosphorylation. Thus, sunitinib reduces the expression of KRT6A and SERPINB1 by inhibiting the ERK1/2 and p38 MAPK signalling pathways in the skin model. These changes in expression contribute to the pathol. of HFSR. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4Safety of 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione).

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ding, Mei et al. published their research in ACS Chemical Biology in 2019 | CAS: 280744-09-4

Regulatory T (Treg) cells, expressing the transcription factor forkhead box p3 (FOXP3), are the key cells regulating peripheral autoreactive T lymphocytes by suppressing effector T cells. FOXP3⁺ Treg cells play essential roles controlling immune responses in autoimmune diseases and cancer. Several clin. approaches (e.g., polyclonal expansion of Treg cells with anti-CD3 and anti-CD28 coated beads in the presence of drugs) are under evaluation. However, expression of FOXP3, recognized as the master regulator of Treg cells, in induced Treg cells have been shown to be instable, and mol. targets involved in regulating FOXP3 expression and Treg cell function have not been well-defined. Thus, new targets directly regulating FOXP3 expression and the expression of its downstream genes (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA4)) have the potential to stabilize the Treg cell phenotype and function. This report describes the development of an automated medium-throughput 384-well plate flow cytometry phenotypic assay measuring the protein expression of FOXP3 and CTLA4 in human Treg cells. Screening a library of 4213 structurally diverse compounds allowed us to identify a variety of compounds regulating FOXP3 and CTLA4 expression. Further evaluation of these and related small mols., followed by confirmation using siRNA-mediated gene knockdown, revealed three targets: euchromatic histone-lysine N-methyltransferase (EHMT2) and glycogen synthase kinase 3 alpha/beta (GSK3α/β) as potent pos. regulators of FOXP3 expression, and bromodomain and extra-terminal domain (BET) inhibitors as neg. regulators of FOXP3 and CTLA4 expression. These targets have potential implications for establishing novel therapies for autoimmune diseases and cancer. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4COA of Formula: C19H12Cl2N2O2).

Yuan, Jifang et al. published their research in Biomaterials Science in 2020 | CAS: 280744-09-4

Small mols. play remarkable roles in promoting tissue regeneration, but are limited by their burst release. Various bioactive mols. are required to create a suitable niche for better skin regeneration by controlling their release behaviors. Herein, a small mol. SB216763, a GSK-3 inhibitor, was loaded on silk fibroin nanofibers (SNF), and then mixed with chitosan (CS) to prepare the small mol.-loaded composite bionic scaffolds (CSNF-SB). Given the interaction of SNF and SB216763, the sustained release of SB216763 for more than 21 days was achieved for SNF and CSNF-SB composite scaffolds. Compared to drug-free CSNF scaffolds, CSNF-SB showed better cell adhesion and proliferation capacity, suggesting bioactivity. The upregulated expression of β-catenin in fibroblasts in vitro revealed that the released small mols. maintained their function in composite scaffolds. Quicker and better wound healing was realized with the drug-loaded scaffolds, which was significantly superior to that treated with drug-free scaffolds. Unlike the DFO-loaded silk hydrogel system, hair follicle neogenesis was also found in the drug-loaded-scaffold treatment wounds, demonstrating functional recovery. Therefore, silk nanofibers as versatile carriers for different small bioactive mols. could be used to fabricate scaffolds with optimized niches and then achieve functional recovery of tissues. The small mol.-loaded bionic scaffolds have a promising future in skin tissue regeneration. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4HPLC of Formula: 280744-09-4).

Tong, Jingshan et al. published their research in Molecular Cancer Therapeutics in 2017 | CAS: 280744-09-4

Heat shock protein 90 (Hsp90) is widely overexpressed in cancer cells and necessary for maintenance of malignant phenotypes. Hsp90 inhibition induces tumor cell death through degradation of its client oncoproteins and has shown promises in preclin. studies. However, the mechanism by which Hsp90 inhibitors kill tumor cells is not well-understood. Biomarkers associated with differential sensitivity and resistance to Hsp90 inhibitors remain to be identified. In this study, we found that colorectal cancer cells containing inactivating mutations of FBW7, a tumor suppressor and E3 ubiquitin ligase, are intrinsically insensitive to Hsp90 inhibitors. The insensitive colorectal cancer cells lack degradation of Mcl-1, a prosurvival Bcl-2 family protein. Hsp90 inhibition promotes GSK3β-dependent phosphorylation of Mcl-1, which subsequently binds to FBW7 and undergoes ubiquitination and proteasomal degradation Specifically blocking Mcl-1 phosphorylation by genetic knock-in abrogates its degradation and renders in vitro and in vivo resistance to Hsp90 inhibitors, which can be overcame by Mcl-1-selective small-mol. inhibitors. Collectively, our findings demonstrate a key role of GSK3β/FBW7-dependent Mcl-1 degradation in killing of colorectal cancer cells by Hsp90 inhibitors and suggest FBW7 mutational status as a biomarker for Hsp90-targeted therapy. In the experiment, the researchers used many compounds, for example, 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (cas: 280744-09-4Recommanded Product: 280744-09-4).

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