Tag: M.W=350-400

Kim, Se Hun published the artcileSynthesis of Alocasin A, Product Details of C20H28BNO5, the publication is Journal of Natural Products (2015), 78(12), 3080-3082, database is CAplus and MEDLINE.

Herein is reported a synthesis of alocasin A (I), an alkaloid component of Alocasia macrorrhiza, a herbaceous plant used in folk medicine throughout southern Asia. A double Suzuki-Miyaura cross-coupling reaction between a 3-borylindole and 2,5-dibromopyrazine was used to assemble the heteroaromatic framework of the natural product. Removal of the protecting groups gave a synthetic sample of I, the spectroscopic data of which matched those in the isolation report of this compound

Journal of Natural Products published new progress about 1256359-99-5. 1256359-99-5 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Amide,Ether,Boronic Acids,Boronate Esters, name is tert-Butyl 5-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate, and the molecular formula is C20H28BNO5, Product Details of C20H28BNO5.

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

Kim, Se Hun published the artcileSynthesis of scalaridine A, COA of Formula: C20H28BNO5, the publication is Tetrahedron Letters (2015), 56(43), 5914-5915, database is CAplus.

A synthesis of the pyridine-linked bisindole alkaloid scalaridine A is described. An iridium catalyzed, directed C-H borylation of N-Boc-5-methoxyindole gave the corresponding 3-borylindole, which underwent a one-pot, double Suzuki-Miyaura cross-coupling reaction with 3,5-dibromopyridine to install the entire heteroaromatic framework of the natural product. Removal of the protecting groups gave a synthetic sample of scalaridine A, which was spectroscopically identical to that described in the isolation report.

Tetrahedron Letters published new progress about 1256359-99-5. 1256359-99-5 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Amide,Ether,Boronic Acids,Boronate Esters, name is tert-Butyl 5-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate, and the molecular formula is C20H28BNO5, COA of Formula: C20H28BNO5.

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

Muscella, A. published the artcileRole of epidermal growth factor receptor signaling in a Pt(II)-resistant human breast cancer cell line, Recommanded Product: SU6656, the publication is Biochemical Pharmacology (Amsterdam, Netherlands) (2021), 114702, database is CAplus and MEDLINE.

Platinum complexes are currently used for breast cancer therapy, but, as with other drug classes, a series of intrinsic and acquired resistance mechanisms hinder their efficacy. To better understand the mechanisms underlying platinum complexes resistance in breast cancer, we generated a [Pt(O,O’-acac)(γ-acac)(DMS)]-resistant MCF-7, denoted as [Pt(acac)2]R. [Pt(O,O’-acac)(γ-acac)(DMS)] was chosen as previous works showed that it has distinct mechanisms of action from cisplatin, especially with regard to cellular targets. [Pt(acac)2]R cells are characterized by increased proliferation rates and aggressiveness with higher PKC-δ, BCL-2, MMP-9 and EGFR protein expressions and also by increased expression of various genes covering cell cycle regulation, invasion, survival, and hormone receptors. These [Pt(acac)2]R cells also displayed high levels of activated signaling kinases Src, AKT and ERK/2. [Pt(acac)2]R cells incubated with [Pt(O,O’-acac)(γ-acac)(DMS)], showed a relevant EGFR activation due to PKC-δ and Src phosphorylation that provoked proliferation and survival through MERK1/2/ERK1/2 and PI3K/Akt pathways. In addition, EGFR shuttled from the plasma membrane to the nucleus maybe acting as co-transcriptional factor. The data suggest that growth and survival of resistant cells rely upon a remarkable increase in EGFR level which, in collaboration with an enhanced role of PKC-δ and Src kinases support [Pt(acac)2]R cell. It could therefore be assumed that combination treatments targeting both EGFR and PKC-δ/Src can improve therapy for breast cancer patients.

Biochemical Pharmacology (Amsterdam, Netherlands) 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, 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

Bilsland, Alan E. published the artcileMathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms, Name: SU6656, the publication is PLoS Computational Biology (2014), 10(2), e1003448/1-e1003448/19, 19 pp., database is CAplus and MEDLINE.

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Math. modeling provides an attractive approach for anal. of complex systems and some models may prove useful in systems pharmacol. approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their resp. promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analyzed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR anal. of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may program TERT for transcriptional stability.

PLoS Computational Biology 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, 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

Everett, Steven A. published the artcileControlling the rates of reductively-activated elimination from the (indol-3-yl)methyl position of indolequinones, Product Details of C18H16N2O6, the publication is Journal of the Chemical Society, Perkin Transactions 2 (2001), 843-860, database is CAplus.

A series of substituted 3-(4-nitrophenyloxy)methylindole-4,7-diones (Q) were synthesized. The effects of substitution patterns on the indole core on rates of elimination of 4-nitrophenol as a model for drug release following fragmentation of a phenolic ether linker were studied. After reduction to either the radical anion (Q√^–) or hydroquinone (QH₂) elimination of 4-nitrophenol occurred from the (indol-3-yl)methyl position. The half-lives of Q√^– radicals at [O₂] ≈ 5 mmol dm^-3, typical of tumor hypoxia, were t_1/2 ≈ 0.3-1.8 ms, the higher values associated with higher reduction potentials. Half-lives for the autoxidation of the QH₂ were markedly longer at the same oxygen concentration (t₁/2 ≈ 8-102 min) and longer still in the presence of 4 mmol dm^-3 superoxide dismutase (t_1/2 ≈ 8-19 h). Although the indolequinones were able to eliminate 4-nitrophenol with high efficiency only Q√^– radicals of the 3-carbonyl substituted derivatives did so with sufficiently short half-lives (t_1/2 41-2 ms) to compete with electron transfer to oxygen and therefore have the potential to target the leaving group to hypoxic tissue. The hydroquinones are not sufficiently oxygen sensitive to prevent the elimination of 4-nitrophenol (t_1/2 1.5-3.5 s) even at oxygen concentrations expected in normal tissue. By incorporating electron rich substituents at the indolyl carbonyl position it is possible to control the rate of reductive fragmentation. This may prove an important factor in the design of an indolequinone-based bioreductive drug delivery system.

Journal of the Chemical Society, Perkin Transactions 2 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, Product Details of C18H16N2O6.

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

Yoshida, Keiichiro published the artcilePlasmodium induced by SU6656, an Src family kinase inhibitor, is accompanied by a contractile ring defect, Quality Control of 330161-87-0, the publication is Cell Biochemistry and Function (2012), 30(1), 33-40, database is CAplus and MEDLINE.

We have shown that SU6656, a potent Src family kinase inhibitor, has the ability to induce multinucleation at a high frequency in diverse cells: rat skin fibroblasts, bone marrow adherent cells, 5F9A mesenchymal stem cell-like clones, 2C5 tracheal epithelial cells and MDCK epithelial cells from dog kidney. To gain insight into the mechanism of multinucleation, we observed the process by time-lapse and confocal microscopy. These multinuclei generally seem to exist independently in one cell without any connections with each other. By time-lapse microscopy, multinucleated cells were found to be formed through the mechanism of plasmodium: karyokinesis without cytokinesis. The observation of EGFP-actin transfected cells by time-lapse confocal laser scanning microscopy suggested that plasmodium occurred with deficient contractile ring formation. Although we examined the differentiation of these cells, the multinucleated cells could not be categorized into any type of cell in vivo known to exhibit multinuclei. Copyright © 2011 John Wiley & Sons, Ltd.

Cell Biochemistry and Function 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 C9H20Cl2Si, 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

Fassbender, Svenja I. published the artcileGeometric E→Z Isomerisation of Alkenyl Silanes by Selective Energy Transfer Catalysis: Stereodivergent Synthesis of Triarylethylenes via a Formal anti-Metallometallation, Category: indole-building-block, the publication is Angewandte Chemie, International Edition (2019), 58(51), 18619-18626, database is CAplus and MEDLINE.

An efficient geometrical E→Z isomerization of alkenyl silanes is disclosed via selective energy transfer using an inexpensive organic sensitizer. Characterized by operational simplicity, short reaction times (2 h), and broad substrate tolerance, the reaction displays high selectivity for trisubstituted systems (Z/E up to 95:5). In contrast to thermal activation, directionality results from deconjugation of the π-system in the Z-isomer due to A^1,3-strain thereby inhibiting re-activation. The structural importance of the β-substituent logically prompted a study of mixed bis-nucleophiles (Si, Sn, B). These versatile linchpins also undergo facile isomerization, thereby enabling a formal anti-metallometalation. Mechanistic interrogation, supported by a theor. study, is disclosed together with application of the products to the stereospecific synthesis of biol. relevant target structures.

Angewandte Chemie, International Edition published new progress about 1256359-23-5. 1256359-23-5 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Sulfamide,Benzene,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is 1-(Phenylsulfonyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C20H22BNO4S, Category: 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

Swann, Elizabeth published the artcileRates of reductive elimination of substituted nitrophenols from the (indol-3-yl)methyl position of indolequinones, Recommanded Product: 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, the publication is Journal of the Chemical Society, Perkin Transactions 2 (2001), 1340-1345, database is CAplus.

A series of indolequinones bearing substituted nitrophenols on the (indol-3-yl)methyl position (I;R¹,R²,R³,R⁴,R⁵ given: H,NO₂,H,NO₂,H; H,MeO,H,H,NO₂;H,MeO,H,NO₂,H; Me,F,H,NO₂,H; H,CHO,H,NO₂,H; etc. )was synthesized. The nitrophenol leaving groups were appropriately substituted to give a wide range (4 units) in phenolic pK_a value. The rate of reductive elimination of phenoxide anions from the (indol-3-yl)methyl position of semiquinone radicals was dependent upon this pK_a, with a decrease in 3.8 pK units shortening the half-life from 28 to 1.5 ms. Only 2,4-dinitrophenol (pK_a = 3.9) was eliminated from an unsubstituted (indol-3-yl)methyl position at a rate that would compete with reoxidation of the radical by oxygen. A nitrothiophenol leaving group was eliminated comparatively slowly and only from the hydroquinone. These studies demonstrate the dependence upon leaving group pK_a of the rate of reductive elimination from the (indol-3-yl)methyl position of indolequinones.

Journal of the Chemical Society, Perkin Transactions 2 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 C13H17BO2, Recommanded Product: 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione.

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

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