Tag: M.W=350-400

Niggenaber, Janina published the artcileComplex Crystal Structures of EGFR with Third-Generation Kinase Inhibitors and Simultaneously Bound Allosteric Ligands, Synthetic Route of 1942114-09-1, the publication is ACS Medicinal Chemistry Letters (2020), 11(12), 2484-2490, database is CAplus and MEDLINE.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) and currently the gold-standard for the treatment of patients suffering from non-small cell lung cancer (NSCLC) harboring T790M-mutated epidermal growth factor receptor (EGFR). The outcome of the treatment, however, is limited by the emergence of the C797S resistance mutation. Allosteric inhibitors have a different mode of action and were developed to overcome this limitation. However, most of these innovative mols. are not effective as a single agent. Recently, mutated EGFR was successfully addressed with osimertinib combined with the allosteric inhibitor JBJ-04-125-02, but surprisingly, structural insights into their binding mode were lacking. Here, we present the first complex crystal structures of mutant EGFR in complex with third-generation inhibitors such as osimertinib and mavelertinib in the presence of simultaneously bound allosteric inhibitors. These structures highlight the possibility of further combinations targeting EGFR and lay the foundation for hybrid inhibitors as next-generation TKIs.

ACS Medicinal Chemistry Letters published new progress about 1942114-09-1. 1942114-09-1 belongs to indole-building-block, auxiliary class Indoline,Thiazole,Fluoride,Amine,Benzene,Amide,Alcohol,Protein Tyrosine Kinase/RTK, name is 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide, and the molecular formula is C19H14FN3O3S, Synthetic Route of 1942114-09-1.

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

Kuroda, Yoshiyuki published the artcileRegulation of hyaluronan production by β2 adrenergic receptor signaling, Related Products of indole-building-block, the publication is Biochemical and Biophysical Research Communications (2021), 50-55, database is CAplus and MEDLINE.

Hyaluronan (HA), the main component of the extracellular matrix, is involved in tissue elasticity and cell scaffolding, and in progression of conditions such as cancer, inflammation and wound healing. Signaling by G protein coupled receptor (GPCR) activation increases expression of hyaluronan synthase (HAS) and HA production The β2 adrenergic receptor (β2AR) is a catecholamine-liganded GPCR that is involved in cancer progression and wound healing. Since HA and β2AR are involved in a common pathol., we investigated whether β2AR signaling regulates HA production After stimulating β2AR-expressing cells with a β agonist, the amount of HA in the culture medium was measured and HAS expression was examined by real-time PCR. A variety of signaling mol. inhibitors were used to identify signaling pathways that alter HAS expression.β2AR activation increased HA production and enhanced HAS2 expression. The increase in HAS2 expression by β2AR activation occurred via the Gs – adenylyl cyclase – PKA – CREB signal transduction pathway. Downstream signal transduction by β2AR activation increased HA production by enhancing transcription of the HAS2 gene. This study suggests that β2AR is a GPCR that regulates HA production, and that stimulation with a catecholamine (β2 agonist) can regulate HA productionβ2AR may function through regulation of HA production in cancer progression and wound healing.

Biochemical and Biophysical Research Communications 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

Han, Aishan published the artcilePhosphate-affinity electrophoresis on a microchip for determination of protein kinase activity, Formula: C19H21N3O3S, the publication is Electrophoresis (2009), 30(20), 3507-3513, database is CAplus and MEDLINE.

We describe microchip-based phosphate-affinity electrophoresis (μPAE) for separation of peptides aimed at determination of kinase activity. The μPAE exploits two recently published technologies: autonomous sample injection for PDMS microchips and a phosphate-specific affinity ligand, Phos-tag. We prepared a fluorescently labeled substrate peptide, specific to human c-Src, and its phosphorylated form. We synthesized a Phos-tag-poly(dimethylacrylamide) conjugate. The conjugate and the sample solutions were autonomously injected into a PDMS-glass hybrid microchip. The two solutions were contacted together in the microchannel. When the peptides were electrophoresed into the Phos-tag-poly(dimethylacrylamide) region, the phosphorylated peptide was specifically trapped, and separated from the nonphosphorylated peptide in 10 s. The results were quantified by the areas of the fluorescence peaks. The calibration plot obtained with standard samples showed an excellent linearity and a LOD of 0.9% phosphorylated peptide among the total peptides. For c-Src-reacted samples, the results from the μPAE were in good agreement with those from matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The μPAE was also successful in the presence of inhibitors for c-Src. The measured 50% inhibitory concentration values for staurosporine, PP2, and SU6656 were in good agreement with the literature values.

Electrophoresis 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, 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

Teng, Christina T. published the artcileDevelopment of Novel Cell Lines for High-Throughput Screening to Detect Estrogen-Related Receptor Alpha Modulators, Synthetic Route of 330161-87-0, the publication is SLAS Discovery (2017), 22(6), 720-731, database is CAplus and MEDLINE.

Estrogen-related receptor alpha (ERRα), the first orphan nuclear receptor discovered, is crucial for the control of cellular energy metabolism ERRα and its coactivator, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), are required for rapid energy production in response to environmental challenges. They have been implicated in the etiol. of metabolic disorders such as type 2 diabetes and metabolic syndrome. ERRα also plays a role in the pathogenesis of breast cancer. Identification of compounds that modulate ERRα signaling may elucidate environmental factors associated with these diseases. Therefore, we developed stable cell lines containing an intact ERRα signaling pathway, with and without the coactivator PGC-1α, to use as high-throughput screening tools to detect ERRα modulators. The lentiviral PGC-1α expression constructs and ERRα multiple hormone response element (MHRE) reporters were introduced into HEK293T cells that express endogenous ERRα. A cell line expressing the reporter alone was designated “ERR.” A second cell line expressing both reporter and PGC-1α was named “PGC/ERR.” Initial screenings of the Library of Pharmacol. Active Compounds (LOPAC) identified 33 ERR and 22 PGC/ERR agonists, and 54 ERR and 15 PGC/ERR antagonists. Several potent ERRα agonists were dietary plant compounds (e.g., genistein). In conclusion, these cell lines are suitable for high-throughput screens to identify environmental chems. affecting metabolic pathways and breast cancer progression.

SLAS Discovery 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 C14H14N2O2, Synthetic Route 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

Tian, He-Ping published the artcileNon-receptor tyrosine kinase Src is required for ischemia-stimulated neuronal cell proliferation via Raf/ERK/CREB activation in the dentate gyrus, Recommanded Product: SU6656, the publication is BMC Neuroscience (2009), No pp. given, database is CAplus and MEDLINE.

Background: Neurogenesis in the adult mammalian hippocampus may contribute to repairing the brain after injury. However, Mol. mechanisms that regulate neuronal cell proliferation in the dentate gyrus (DG) following ischemic stroke insult are poorly understood. This study was designed to investigate the potential regulatory capacity of non-receptor tyrosine kinase Src on ischemia-stimulated cell proliferation in the adult DG and its underlying mechanism. Results: Src kinase activated continuously in the DG 24 h and 72h after transient global ischemia, while SU6656, the Src kinase inhibitor significantly decreased the number of bromodeoxyuridine (BrdU) labeling-pos. cells of rats 7 days after cerebral ischemia in the DG, as well as down-regulated Raf phosphorylation at Tyr(340/341) site, and its down-stream signaling mols. ERK and CREB expression followed by 24 h and 72h of reperfusion, suggesting a role of Src kinase as an enhancer on neuronal cell proliferation in the DG via modifying the Raf/ERK/CREB cascade. This hypothesis is supported by further findings that U0126, the ERK inhibitor, induced a reduction of adult hippocampal progenitor cells in DG after cerebral ischemia and down-regulated phospho-ERK and phospho-CREB expression, but no effect was detected on the activities of Src and Raf. Conclusion: Src kinase increase numbers of newborn neuronal cells in the DG via the activation of Raf/ERK/CREB signaling cascade after cerebral ischemia.

BMC Neuroscience 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 C11H21BF4N2O2, Recommanded Product: 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

Chang, Hua-Ching published the artcileSpleen tyrosine kinase mediates the actions of EPO and GM-CSF and coordinates with TGF-β in erythropoiesis, HPLC of Formula: 330161-87-0, the publication is Biochimica et Biophysica Acta, Molecular Cell Research (2017), 1864(4), 687-696, database is CAplus and MEDLINE.

Erythropoietin (EPO) and GM-CSF are involved in erythropoiesis, while TGF-β inhibits proliferation but potentiates differentiation of erythroblasts. Since Syk inhibitor may induce anemia side effect in clinic, here we investigated the role of Syk in the biol. actions of EPO and GM-CSF in erythropoiesis. In human erythroleukemia cell line TF-1, Syk inhibitor R406 exerts an enhancement effect with TGF-β to decrease cell viability, either in the absence or presence of EPO or GM-CSF. Such effect of R406 results from the reduced cell cycle progression and increased cell apoptosis. Notably, unlike Syk, Src family kinases are not involved in the viability control of TF-1 cells. Signaling studies showed that Syk is required for STAT5 and ERK activation induced by EPO, and Akt and ERK activation induced by GM-CSF. Nevertheless, R406 does not change the Smad2/3 signal caused by TGF-β, and TGF-β neither affects above signal pathways of EPO and GM-CSF. Of note, Syk is constitutively associated with EPOR in plasma membrane and can bind to STAT5 at active status upon EPO stimulation. Furthermore, EPO-induced Hb γ expression was reduced by R406. In BFU-E and CFU-E colony formation assays in Syk-deficient erythroid progenitor cells, we confirmed the essential role of Syk in erythropoiesis mediated by EPO. Taken together, Syk is a novel upstream signaling mol. of EPOR, and contributes to erythroblast proliferation, survival and differentiation.

Biochimica et Biophysica Acta, Molecular Cell Research 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, HPLC of Formula: 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

Takadera, Tsuneo published the artcileApoptosis Induced by Src-Family Tyrosine Kinase Inhibitors in Cultured Rat Cortical Cells, Recommanded Product: SU6656, the publication is Neurotoxicity Research (2012), 21(3), 309-316, database is CAplus and MEDLINE.

In the central nervous system, members of the Src family of tyrosine kinases (SFKs) are widely expressed and are abundant in neurons. The purpose of this study is to examine whether glycogen synthase-3 (GSK-3) is involved in SFK inhibitor-induced apoptosis. PP2 and SU6656, SFK inhibitors, increased apoptotic cell death with morphol. changes that were characterized by cell shrinkage, chromatin condensation, or nuclear fragmentation. Moreover, both activation of caspase-9 and caspase-3 were accompanied by the cell death. GSK-3 inhibitors, such as alsterpaullone and SB216763, prevented the PP2-induced apoptosis. In addition, insulin-like growth factor-I prevented the PP2-induced cell death and PP2 inhibited phosphorylation of focal adhesion kinase (FAK). Phosphorylation of FAK on Tyr 576 by Src activates FAK. These results suggest that inhibition of SFK induces apoptosis possibly via blocking of FAK/phosphatidylinositol-3 kinase/Akt signaling pathway and activation of GSK-3 is involved in the cell death in rat cortical neurons.

Neurotoxicity Research 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 C12H9N3O4, Recommanded Product: 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

Takeuchi, Yoshinori published the artcileScreening of therapeutic targets for canine mast cell tumors from a variety of kinase molecules, Quality Control of 330161-87-0, the publication is Journal of Veterinary Medical Science (2011), 73(10), 1295-1302, database is CAplus and MEDLINE.

Options of systemic treatment for canine MCT have been still limited and most canine cases with MCTs eventually undergo relapses even after achievement of a remission. Thus addnl. therapies are required to establish for the tumor. To identify the novel candidate therapeutic targets for canine MCT, the mRNA expression and phosphorylation statuses of several receptor or non-receptor kinases as well as the inhibitory effect of 95 specific inhibitors on the growth were assessed in three canine MCT cell lines (HRMC, VIMC1 and CMMC1). Among the 14 targets, the mRNAs of 11, 7 and 7 kinases were amplified in HRMC, VIMC1 and CMMC1, resp. The mRNAs of VEGFR3, PDGFRα, SRC, YES, LCK and FYN were detected in all cell lines. The phosphorylation of 12, 8 and 7 kinases was observed by using specific antibody arrays in HRMC, VIMC1 and CMMC1, resp. DTK, EPHB6, AMPKα1, CREB, STAT5a and STAT5b were phosphorylated in all cell lines. The 10, 9 and 17 inhibitors exhibited the biol. activity against the growth of HRMC, VIMC1 and CMMC1, resp. Only three inhibitors such as SB218078 (for Chk1), PDGF RTK inhibitor IV (for PDGFR) and radicicol (for Hsp90) suppressed the growth of all three cell lines. The present study indicated that several kinases, such as Chk1, PDGFR and Hsp90, could be used as therapeutic targets in the treatment for canine MCT. Further studies and clin. trials are warranted to apply the inhibitors for the treatment of the tumor.

Journal of Veterinary Medical Science 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 C38H74Cl2N2O4, 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

Tamm, Christoffer published the artcileDifferential effects on cell motility, embryonic stem cell self-renewal and senescence by diverse Src kinase family inhibitors, HPLC of Formula: 330161-87-0, the publication is Experimental Cell Research (2012), 318(4), 336-349, database is CAplus and MEDLINE.

The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying mol. mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt in proliferation of fibroblast and epithelial cells in the center of the colonies approx. 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2.

Experimental Cell Research 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 C7H7IN2O, HPLC of Formula: 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

Zhang, Huairong published the artcileIdentification of differentially expressed kinase and screening potential anticancer drugs in papillary thyroid carcinoma, Name: SU6656, the publication is Disease Markers (2016), 2832980/1-2832980/9, database is CAplus and MEDLINE.

We aim to identify protein kinases involved in the pathophysiol. of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible mol. mechanisms. The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway anal. The functional enrichment anal. indicated that “mitogen-activated protein kinases pathway” expression was extremely enriched, followed by “neurotrophin signaling pathway,” “focal adhesion,” and “GnRH signaling pathway.”. MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly regulated to correct these pathways. Kinases investigated by the literature on carcinoma were considered to be potential novel mol. therapeutic target in PTC and application of corresponding kinase inhibitors could be possible therapeutic tool. SRC,MAPK, and EGFR were the most important differentially expressed kinases in PTC. Combined inhibitors may have high efficacy in PTC treatment by targeting these kinases.

Disease Markers 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 C20H21ClN4O4, 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