Tag: M.W=350-400

Guntur, Vamsi P. published the artcileThe potential use of tyrosine kinase inhibitors in severe asthma, Application of SU6656, the publication is Current Opinion in Allergy and Clinical Immunology (2012), 12(1), 68-75, database is CAplus and MEDLINE.

Purpose of review: Severe asthma comprises heterogeneous phenotypes that share in common a poor response to traditional therapies. Recent and ongoing work with tyrosine kinase inhibitors suggests a potential beneficial role in treatment of severe asthma. Recent findings: Various receptor and nonreceptor tyrosine kinase pathways contribute to aspects of airway inflammation, airway hyperresponsiveness, and remodeling of asthma. Selective and nonselective tyrosine kinase inhibitors may be useful to block pathways that are pathol. overactive or overexpressed in severe asthma. Recent in-vivo studies have demonstrated the utility of inhibitors against specific tyrosine kinases (epidermal growth factor receptor, c-kit/platelet derived growth factor receptor, vascular endothelial growth factor receptor, spleen tyrosine kinase, and janus kinase) in altering key aspects of severe asthma. Summary: Asthma and even severe asthma does not consist of a single phenotype. Targeting key inflammatory and remodeling pathways engaged across subphenotypes with tyrosine kinase inhibitors appears to hold promise.

Current Opinion in Allergy and Clinical Immunology published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Application of SU6656.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Bartscht, Tobias published the artcileTGF-β Signal Transduction in Pancreatic Carcinoma Cells is Sensitive to Inhibition by the Src Tyrosine Kinase Inhibitor AZM475271, Application In Synthesis of 330161-87-0, the publication is Anti-Cancer Agents in Medicinal Chemistry (2017), 17(7), 966-972, database is CAplus and MEDLINE.

Background: Earlier results from our group have shown that in pancreatic ductal adenocarcinoma (PDAC)-derived cells transforming growth factor (TGF)-β1-dependent epithelial-mesenchymal transition (EMT) and cell motility was inhibited by the Src inhibitors PP2 and PP1 both of which targeted the TGF-β receptors for inhibition. Objective: In this study we evaluated the impact of another Src inhibitor, AZM475271, on various TGF-β responses in PDAC cells. Method: The effect of AZM475271 on TGF-β1-induced random cell migration (chemokinesis), the expression of EMT and migration/invasion-associated genes, TGF-β-induced luciferase activity, and C-terminal phosphorylation of Smad2 and Smad3 was measured in the PDAC-derived Panc-1 and Colo357 cell lines using real-time cell migration assays, quant. real-time PCR, luciferase reporter gene assays and phosphoimmunoblotting, resp. Results: AZM475271 effectively blocked TGF-β1-induced chemokinesis of Panc-1 cells in a dose-dependent fashion and inhibited the high chemokinetic activity of Panc-1 cells with ectopic expression of a constitutively active ALK5T204D mutant. AZM475271 but not another Src inhibitor, SU6656, partially relieved the suppressive effect of TGF-β1 on E-cadherin and inhibited TGF-β1-induced upregulation of the MMP2, MMP9, N-cadherin and vimentin genes, activity of a TGF-β1-dependent reporter gene, and activation of Smad2 and Smad3. Conclusion: Our data suggest that AZM475271 cross-inhibits tumor-promoting TGF-β signaling and may thus function as an inhibitor of both TGF-β and Src in both exptl. and clin. therapies against metastatic dissemination in late-stage PDAC.

Anti-Cancer Agents in Medicinal Chemistry published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Application In Synthesis of 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Bilsland, Alan E. published the artcileIdentification of a Selective G1-Phase Benzimidazolone Inhibitor by a Senescence-Targeted Virtual Screen Using Artificial Neural Networks, Computed Properties of 330161-87-0, the publication is Neoplasia (New York, NY, United States) (2015), 17(9), 704-715, database is CAplus and MEDLINE.

Cellular senescence is a barrier to tumorigenesis in normal cells, and tumor cells undergo senescence responses to genotoxic stimuli, which is a potential target phenotype for cancer therapy. However, in this setting, mixed-mode responses are common with apoptosis the dominant effect. Hence, more selective senescence inducers are required. Here we report a machine learning-based in silico screen to identify potential senescence agonists. We built profiles of differentially affected biol. process networks from expression data obtained under induced telomere dysfunction conditions in colorectal cancer cells and matched these to a panel of 17 protein targets with confirmatory screening data in PubChem. We trained a neural network using 3517 compounds identified as active or inactive against these targets. The resulting classification model was used to screen a virtual library of ∼ 2M lead-like compounds One hundred and forty-seven virtual hits were acquired for validation in growth inhibition and senescence-associated β-galactosidase assays. Among the found hits, a benzimidazolone compound, CB-20903630, had low micromolar IC50 for growth inhibition of HCT116 cells and selectively induced senescence-associated β-galactosidase activity in the entire treated cell population without cytotoxicity or apoptosis induction. Growth suppression was mediated by G1 blockade involving increased p21 expression and suppressed cyclin B1, CDK1, and CDC25C. In addition, the compound inhibited growth of multicellular spheroids and caused severe retardation of population kinetics in long-term treatments. Preliminary structure-activity and structure clustering analyses are reported, and expression anal. of CB-20903630 against other cell cycle suppressor compounds suggested a PI3K/AKT-inhibitor-like profile in normal cells, with different pathways affected in cancer cells.

Neoplasia (New York, NY, United States) published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Computed Properties of 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Bian, Jinlei published the artcileDiscovery of NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors with novel chemical scaffolds by shape-based virtual screening combined with cascade docking, Quality Control of 192820-78-3, the publication is RSC Advances (2015), 5(61), 49471-49479, database is CAplus.

A number of novel NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors were discovered from the ChemDiv database via a simple protocol. Based on two reference NQO1 inhibitors, dicoumarol (DIC) and ES936, a shape-based similarity search and cascade docking filtering were conducted to identify new NQO1 inhibitors. Using these techniques, 43 compounds were selected, ordered, and tested. Among them, 7 compounds with novel chem. scaffolds were confirmed to be active by in vitro assays. Determination of the ability for protecting against NQO1-mediated toxicity of β-lapachone (β-lap) confirmed that compounds 8, 10 and 13 may be pharmacol. useful for probing the function of NQO1 in cells.

RSC Advances published new progress about 192820-78-3. 192820-78-3 belongs to indole-building-block, auxiliary class Fused/Partially Saturated Cycles,Dihydroindoles, name is 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, and the molecular formula is C18H16N2O6, Quality Control of 192820-78-3.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Fossey, Stacey L. published the artcileCharacterization of STAT3 activation and expression in canine and human osteosarcoma, Related Products of indole-building-block, the publication is BMC Cancer (2009), No pp. given, database is CAplus and MEDLINE.

Dysregulation of signal transducer and activator of transcription 3 (STAT3) has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA) tissues and cell lines. OSA in the canine population is known to exhibit a similar clin. behavior and mol. biol. when compared to its human counterpart, and is often used as a model for preclin. testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biol. activity of a novel small mol. STAT3 inhibitor. To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small mol. Src (SU6656) or STAT3 (LLL3) inhibitors and cell proliferation (CyQUANT), caspase 3/7 activity (ELISA), apoptosis (Western blotting for PARP cleavage) and/or viability (Wst-1) were determined Addnl., STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymog. Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known transcriptional targets of STAT3. These data suggest that STAT3 activation contributes to the survival and proliferation of human and canine OSA cells, thereby providing a potentially promising target for therapeutic intervention. Future investigational trials of LLL3 in dogs with spontaneous OSA will help to more accurately define the role of STAT3 in the clin. setting.

BMC Cancer published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Related Products of indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Li, Youxin published the artcileCharacterization of tyrosine kinase and screening enzyme inhibitor by capillary electrophoresis with laser-induced fluoresce detector, Application of SU6656, the publication is Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences (2011), 879(1), 107-112, database is CAplus and MEDLINE.

An effective, rapid and reliable capillary electrophoresis-laser induced fluorescence (CE-LIF) procedure was built to study the characterization of tyrosine kinase (TK), which was a target for drug screening. In this procedure, CE separated the sample of the TK reaction and LIF selectively detected the fluorescence-labeled polypeptide substrate and product. The precise TK activity was quantitated by introducing the transformation ratio of the substrate (T%) to avoid the deviation resulting from the detection sensitivity and the injection amounts in different runs and different capillaries. By measuring the T%, the effects of various reaction conditions were optimized. Meanwhile, the progression of the enzyme reaction was monitored. The K_m and V_max were calculated for TK under the optimized exptl. conditions. In addition, the inhibition effectiveness of two model inhibitors, staurosporine and SU6656 were evaluated. The results indicated that the screening platform based on electrophoresis was suitable for TK anal. and laid a foundation for the high-throughput screening (HTS) of TK inhibitors.

Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Application of SU6656.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Li, Wei published the artcileHIV-1 uses dynamic podosomes for entry into macrophages, Computed Properties of 330161-87-0, the publication is Journal of Virology (2021), 95(10), e02480, database is CAplus and MEDLINE.

Macrophages are one of the major targets of human immunodeficiency virus 1 (HIV-1) and play crucial roles in viral dissemination and persistence during AIDS progression. Here, we reveal the dynamic podosome-mediated entry of HIV-1 into macrophages. Inhibition of podosomes prevented HIV-1 entry into macrophages, while stimulation of podosome formation promoted viral entry. Single-virus tracking revealed the temporal and spatial mechanism of the dynamic podosome-mediated viral entry process. The core and ring structures of podosomes played complex roles in viral entry. The HIV coreceptor CCR5 was recruited to form specific clusters at the podosome ring, where it participated in viral entry. The podosome facilitated HIV-1 entry with a rotation mode triggered by dynamic actin. Our discovery of this novel HIV-1 entry route into macrophages, mediated by podosomes critical for cell migration and tissue infiltration, provides a new view of HIV infection and pathogenesis, which may assist in the development of new antiviral strategies.

Journal of Virology published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Computed Properties of 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Sekigawa, Masayuki published the artcileComprehensive screening of human genes with inhibitory effects on yeast growth and validation of a yeast cell-based system for screening chemicals, Name: SU6656, the publication is Journal of Biomolecular Screening (2010), 15(4), 368-378, database is CAplus and MEDLINE.

To evaluate yeast as a high-throughput cell-based system for screening chems. that may lead to drug development, 10,302 full-length human cDNAs (鈭?0% of the total cDNAs) were introduced into yeast. Approx. 5.6% (583 clones) of the cDNAs repressed the growth of yeast. Notably, 鈭?5% of the repressive cDNAs encoded uncharacterized proteins. Small chems. can be readily surveyed by monitoring their restorative effects on the growth of yeast. The authors focused on protein kinases because protein kinases are involved in various diseases. Among 263 protein kinase cDNAs (鈭?0% of the total) expressed in yeast, 60 cDNAs (鈭?3%), including c-Yes, a member of the Src tyrosine kinase family, inhibited the growth of yeast. Known inhibitors for protein kinases were examined for whether they reversed the c-Yes-induced inhibition of the yeast growth. Among 85 inhibitors tested, 6 compounds (PP2, PP1, SU6656, purvalanol, radicicol, and geldanamycin) reversed the inhibition, indicating a high specificity sufficient for validating this screening system. Human c-Yes was found to interact with Hsc82, one of the yeast chaperones. Radicicol and geldanamycin probably exerted their actions through interactions with Hsc82. These results indicate that when human proteins requiring mol. chaperones for their activities are subjected to the yeast screening system, 2 groups of chems. may be found. The actions of one group are exerted through direct interactions with the human proteins, whereas those of the other group are mediated through interactions with chaperones.

Journal of Biomolecular Screening published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C22H12F6O6S2, Name: SU6656.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Martic, S. published the artcileElectrochemical investigations of sarcoma-related protein kinase inhibition, COA of Formula: C19H21N3O3S, the publication is Electrochimica Acta (2011), 56(28), 10676-10682, database is CAplus.

An electrochem. biosensor was developed for the determination of sarcoma (Src)-related protein kinase-catalyzed phosphorylation reactions in the presence of adenosine 5′-纬-ferrocenoyl triphosphate (Fc-ATP). The sensing platform is based on a highly specific amino acid sequence Glu-Gly-Ile-Tyr-Asp-Val-Pro (EGIYDVP), to which a Fc-PO₂ moiety can be transferred from Fc-ATP by the action of the Src kinase. The enzyme kinetics and kinase inhibition were investigated by square wave voltammetry (SWV). The kinetic parameters K_m and V_max were determined for Src protein kinase with respect to Fc-ATP co-substrate and were found to be 200 渭M and 115 渭A cm^-2 min, for phosphorylation of the EGIYDVP peptide substrate. Furthermore, the Src-catalyzed phosphorylation of Tyr was investigated in the presence of the small mol. inhibitors PP1, PP2, SU6656, and roscovitine. PP3 does not inhibit Src activity and was used as a control. The percent inhibition at half concentration, IC₅₀, values were determined for all inhibitors under the study and were estimated to be in the 5-30 nM range. The electrochem. study suggests that the increase in inhibition efficiency was in the order PP3 < SU6656 < roscovitine < PP2 < PP1.

Electrochimica Acta published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, COA of Formula: C19H21N3O3S.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Loerke, Dinah published the artcileQuantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation, Quality Control of 330161-87-0, the publication is Science Signaling (2012), 5(231), rs5, 13 pp., database is CAplus and MEDLINE.

The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image anal. tools that do not require fluorescence tagging and that automatically track and characterize three aspects of scattering in live cells: increase in cell motility, loss of cell-cell adhesion and spatial dispersion of cells (the redistribution of cells during scattering). We used these tools to screen a library of drugs and we identified several efficient inhibitors of scattering, which we classified as selective inhibitors of either motility or loss of cell-cell adhesion, or as nonselective inhibitors. We validated the inhibitors and putative targets from this screen in two unrelated model cell lines. Using pharmacol. treatments and RNA interference (RNAi), we found that nonsteroidal anti-inflammatory drugs inhibited cell-cell dissociation, that indirubins inhibited cell motility and that cyclin-dependent kinase 1 and ribosomal S6 kinase were signaling intermediates in HGF-induced cell scattering. This assay is suitable for larger-scale screenings of chem. compounds or RNAi libraries.

Science Signaling published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Quality Control of 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles