Category: 330161-87-0

Abe, Yuichi published the artcileDeep Phospho- and Phosphotyrosine Proteomics Identified Active Kinases and Phosphorylation Networks in Colorectal Cancer Cell Lines Resistant to Cetuximab, Formula: C19H21N3O3S, the publication is Scientific Reports (2017), 7(1), 1-12, database is CAplus and MEDLINE.

Abnormality in cellular phosphorylation is closely related to oncogenesis. Thus, kinase inhibitors, especially tyrosine kinase inhibitors (TKIs), have been developed as anti-cancer drugs. Genomic analyses have been used in research on TKI sensitivity, but some types of TKI resistance have been unclassifiable by genomic data. Therefore, global proteomic anal., especially phosphotyrosine (pY) proteomic anal., could contribute to predict TKI sensitivity and overcome TKI-resistant cancer. In this study, we conducted deep phosphoproteomic anal. to select active kinase candidates in colorectal cancer intrinsically resistant to Cetuximab. The deep phosphoproteomic data were obtained by performing immobilized metal-ion affinity chromatog.-based phosphoproteomic and highly sensitive pY proteomic analyses. Comparison between sensitive (LIM1215 and DLD1) and resistant cell lines (HCT116 and HT29) revealed active kinase candidates in the latter, most of which were identified by pY proteomic anal. Remarkably, genomic mutations were not assigned in most of these kinases. Phosphorylation-based signaling network anal. of the active kinase candidates indicated that SRC-PRKCD cascade was constitutively activated in HCT116 cells. Treatment with an SRC inhibitor significantly inhibited proliferation of HCT116 cells. In summary, our results based on deep phosphoproteomic data led us to propose novel therapeutic targets against cetuximab resistance and showed the potential for anti-cancer therapy.

Scientific Reports 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

Kitazaki, Hirotaro published the artcileA colorimetric assay of protein kinase activity based on peptide-induced coagulation of gold nanorods, Synthetic Route of 330161-87-0, the publication is Colloids and Surfaces, B: Biointerfaces (2012), 7-11, database is CAplus and MEDLINE.

The authors succeeded in applying gold nanorods (NRs) for the detection of protein kinase (PK) activity based on a substrate-induced coagulation mechanism. Because NRs have cationic surface charges due to surface-adsorbed cetyltrimethylammonium bromide (CTAB), phosphorylated substrate peptides, which gain augmented anionic charges by phosphorylation, induce coagulation of the NRs, resulting in a red-to-blue color change of the corresponding NR dispersion. A large absorption coefficient of the NRs at the near-IR region enabled clear-cut detection of the peptide-induced coagulation. IC₅₀ values of several inhibitors of c-Src kinase determined by the present assay are consistent with reported values.

Colloids and Surfaces, B: Biointerfaces 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, 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

Moraes, Eduardo Cruz published the artcileKinase inhibitor profile for human Nek1, Nek6, and Nek7 and analysis of the structural basis for inhibitor specificity, SDS of cas: 330161-87-0, the publication is Molecules (2015), 20(1), 1176-1191, 16 pp., database is CAplus and MEDLINE.

Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(Δ262-1258)-(T162A), Isogranulatimide for hNek6(S206A), andGSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the resp. hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by mol. docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors.

Molecules 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, SDS of cas: 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

Chow, Amanda published the artcileDasatinib inhibits peripapillary scleral myofibroblast differentiation, HPLC of Formula: 330161-87-0, the publication is Experimental Eye Research (2020), 107999, database is CAplus and MEDLINE.

Scleral fibroblast activation occurs in glaucomatous and myopic eyes. Here we perform an unbiased screen to identify kinase inhibitors that reduce fibroblast activation to diverse stimuli in vitro and to in vivo intraocular pressure (IOP) elevation. Primary cultures of peripapillary scleral (PPS) fibroblasts from two human donors were screened using a library of 80 kinase inhibitors to identify compounds that inhibit TGFbeta-induced extracellular matrix (ECM) synthesis. Inhibition of myofibroblast differentiation was verified by alpha smooth muscle actin (aSMA) immunoblot and collagen contraction assay. Three kinase inhibitors were verified to reduce TGFbeta-induced aSMA expression and cellular contractility (rottlerin, PP2, tyrphostin 9). The effect of three Src inhibitors, bosutinib, dasatinib, and SU-6656, on myofibroblast differentiation was evaluated, with only dasatinib significantly inhibiting TGFbeta-induced ECM synthesis, aSMA expression, and cellular contractility at nanomolar dosages. Subconjunctival injection of dasatinib reduced IOP-induced scleral fibroblast proliferation compared to control (4.9 ± 11.1 ng/sclera with 0.1 muM vs. 88.7 ± 38.6 ng/sclera in control, P < 0.0001). Dasatinib inhibits scleral myofibroblast differentiation and there is pharmacol. evidence that this inhibition is not solely due to Src-kinase inhibition.

Experimental Eye 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

Tanasic, Sascha published the artcileDesipramine targets astrocytes to attenuate synaptic plasticity via modulation of the ephrinA3/EphA4 signalling, Synthetic Route of 330161-87-0, the publication is Neuropharmacology (2016), 154-163, database is CAplus and MEDLINE.

Long-term potentiation (LTP), a major cellular correlate of memory storage, depends on activation of the ERK/MAPK signalling pathway, but the cell type-specific localization of activated MAPKs remains unknown. We found that in the CA1 field of the hippocampus, shortly after LTP induction, an increase in the number of MAPK-pos. cells occurred specifically among astrocytes of the stratum radiatum, suggesting a putative role of astrocytes for LTP. Desipramine (DMI) is an antidepressant which is used to treat major depressive disorder, but also other pathologies such as neuropathic pain or attention-deficit/hyperactivity disorder. Tricyclic antidepressants such as DMI may cause memory impairment as a side effect. However, biol. underpinnings of this effect still remain unclear. Here, we show that DMI inhibited the astrocytic MAPK activation and thereby hindered synaptic potentiation. These effects correlated with a reduced neuronal activation in the stratum pyramidale, thereby prompting us to analyze a regulator of LTP located at the astrocyte-neuron interface in the stratum radiatum, namely the ephrinA3/EphA4 signalling pathway. DMI enhanced EphA4 clustering, which favored an increased ephrinA3-mediated EphA4 phosphorylation and elevated EphA4 forward signalling. The co-administration of DMI with the Src inhibitor SU6656, which blocks EphA4 forward signalling, could partially reverse the LTP attenuation, further supporting the targeting of the ephrinA3/EphA4 pathway by DMI. Thus, our findings suggest a putative novel mechanism for DMI to modulate LTP through the regulation of the ephrinA3/EphA4 signalling pathway. A further exploration of the mol. and behavioral consequences of targeting ephrinA3/EphA4 might help to improve the clin. use of DMI.

Neuropharmacology 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 C6H13NO2, 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

Gao, Xiaodong published the artcileUpregulation of ZNF148 in SDHB-deficient gastrointestinal stromal tumor potentiates Forkhead box M1-mediated transcription and promotes tumor cell invasion, Formula: C19H21N3O3S, the publication is Cancer Science (2020), 111(4), 1266-1278, database is CAplus and MEDLINE.

Succinate dehydrogenase (SDH) deficiency is associated with gastrointestinal stromal tumor (GIST) oncogenesis, but the underlying mol. mechanism remains to be further investigated. Here, we show that succinate accumulation induced by SDHB loss of function increased the expression of zinc finger protein 148 (ZNF148, also named ZBP-89) in GIST cells. Meanwhile, ZNF148 is found to be phosphorylated by ERK at Ser306, and this phosphorylation results in ZNF148 binding to Forkhead box M1 (FOXM1). Through the complex formation at the promoter, ZNF148 facilitates Histone H3 acetylation and FOXM1-mediated Snail transcription, which eventually promotes cell invasion and tumor growth. The clin. anal. indicates that SDHB deficiency is associated with elevated ZNF148 levels, and ZNF148-S306 phosphorylation level displays a pos. correlation with poor prognosis in GIST patients. These findings illustrate an unidentified mol. mechanism underlying FOXM1-regulated gene transcription related to GIST cell invasion, which highlights the physiol. effects of SDHB deficiency on the invasiveness of GIST.

Cancer 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 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

Gomes, Joao R. published the artcileBDNF-Induced Intracellular Signaling, Product Details of C19H21N3O3S, the publication is Neuromethods (2019), 161-183, database is CAplus.

The neurotrophin BDNF plays important roles in neuronal survival, growth, and differentiation during development. Furthermore, it has been shown to mediate long-term changes in the synaptic activity in the hippocampus and in other brain regions, which are thought to underlie learning and memory formation. Cultured hippocampal neurons express TrkB receptors and, therefore, constitute a valuable exptl. model to study in vitro BDNF-induced intracellular signaling pathways. In this chapter, we describe (1) the methodol. used to prepare cultured hippocampal neurons from mice (wild-type-WT or transgenic animals) and rats and (2) three different approaches to investigate BDNF signaling: Western blot and Bio-Plex for overall signaling activity and immunocytochem. to analyze where signaling activity takes place in neurons. The Bio-Plex approach allows the simultaneous characterization of different pathways using small sample volumes and within a short period of time.

Neuromethods 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, Product Details of 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

Heiss, Elke H. published the artcilePlumericin inhibits proliferation of vascular smooth muscle cells by blocking STAT3 signaling via S-glutathionylation, Computed Properties of 330161-87-0, the publication is Scientific Reports (2016), 20771, database is CAplus and MEDLINE.

The etiol. of atherosclerosis and restenosis involves aberrant inflammation and proliferation, rendering compounds with both anti-inflammatory and anti-mitogenic properties as promising candidates for combating vascular diseases. A recent study identified the iridoid plumericin as a new scaffold inhibitor of the pro-inflammatory NF-κB pathway in endothelial cells. We here examined the impact of plumericin on the proliferation of primary vascular smooth muscle cells (VSMC). Plumericin inhibited serum-stimulated proliferation of rat VSMC. It arrested VSMC in the G1/G0-phase of the cell cycle accompanied by abrogated cyclin D1 expression and hindered Ser 807/811-phosphorylation of retinoblastoma protein. Transient depletion of glutathione by the electrophilic plumericin led to S-glutathionylation as well as hampered Tyr705-phosphorylation and activation of the transcription factor signal transducer and activator of transcription 3 (Stat3). Exogenous addition of glutathione markedly prevented this inhibitory effect of plumericin on Stat3. It also overcame downregulation of cyclin D1 expression and the reduction of biomass increase upon serum exposure. This study revealed an anti-proliferative property of plumericin towards VSMC which depends on plumericin’s thiol reactivity and S-glutathionylation of Stat3. Hence, plumericin, by targeting at least two culprits of vascular dysfunction -inflammation and smooth muscle cell proliferation -might become a promising electrophilic lead compound for vascular disease therapy.

Scientific Reports 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

Rehni, Ashish K. published the artcileModulation of src-kinase attenuates naloxone-precipitated opioid withdrawal syndrome in mice, Related Products of indole-building-block, the publication is Behavioural Pharmacology (2011), 22(2), 182-190, database is CAplus and MEDLINE.

This study was designed to investigate the effect of 2,3-dihydro-N, N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1H-indol-2-yl)methylene]-1H-indole-5-sulfonamide (SU-6656), a selective inhibitor of src family kinase, on the development of naloxone-induced opioid withdrawal syndrome in mice. Subacute morphine administration followed by a single injection of naloxone (8 mg/kg, i.p.) was used to precipitate the opioid withdrawal syndrome in mice. Behavioral observations were made immediately after naloxone treatment. The withdrawal syndrome was quant. assessed in terms of withdrawal severity score and frequency of jumping, rearing, forepaw licking, and circling. Daily single administration of SU-6656 was continued during the morphine treatment procedure. Injection of naloxone precipitated severe withdrawal in morphine-dependent mice. However, once-daily administration of SU-6656 (1.5, 3, and 6 mg/kg, i.p.) markedly and dose-dependently attenuated the naloxone-induced morphine withdrawal syndrome. Therefore, it seems that an src family-kinase-linked mechanism is involved in the development of physiol. opioid dependence; thus, src family kinase may serve as a potential target to address the pathol. condition of physiol. dependence and abstinence associated with continuous opioid usage.

Behavioural Pharmacology 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

Rehni, Ashish K. published the artcileSU-6656, a Selective Src Kinase Inhibitor, Attenuates Mecamylamine-Precipitated Nicotine Withdrawal Syndrome in Mice, COA of Formula: C19H21N3O3S, the publication is Nicotine & Tobacco Research (2012), 14(4), 407-414, database is CAplus and MEDLINE.

Introduction: Src kinase is reported to regulate neuronal nicotinic acetylcholine receptor activity, which is among the principal receptor systems acted upon by nicotine. Src kinase is documented to mediate the pathogenesis of substance dependence. Therefore, the present study has been designed to investigate the effect of SU-6656, selective src kinase inhibitor, on the development of nicotine dependence in a mouse model of mecamylamine-induced nicotine withdrawal syndrome. Methods: Our exptl. protocol consisted of administration of nicotine (2.5 mg/kg, s.c.), 4 times daily for 7 days. In order to precipitate nicotine withdrawal, mice were given 1 injection of mecamylamine (3 mg/kg, i.p.), 1 h after the last nicotine injection on the test day (Day 8). Behavioral observations were made for a period of 30 min immediately after mecamylamine treatment. Withdrawal syndrome was quantitated in terms of a composite withdrawal severity score (WSS), and withdrawal syndrome-related anxiety was assessed by elevated plus maze test results. Results: SU-6656 markedly and dose dependently (p < .01) attenuated mecamylamine-induced exptl. nicotine withdrawal syndrome in mice measured in terms of WSS and anxiety score. Conclusions: Thus, it is suggested that src kinase is involved in the development of nicotine dependence-induced precipitation of its withdrawal syndrome and thus may serve as a viable pharmacol. target to tackle the problem of nicotine addiction.

Nicotine & Tobacco 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, 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