Month: November 2022

Nycholat, Corwin M. published the artcileA sulfonamide sialoside analogue for targeting Siglec-8 and -F on immune cells, Synthetic Route of 166883-20-1, the publication is Journal of the American Chemical Society (2019), 141(36), 14032-14037, database is CAplus and MEDLINE.

The Siglec family of cell surface receptors have emerged as attractive targets for cell-directed therapies due to their restricted expression on immune cells, endocytic properties, and ability to modulate receptor signaling. Human Siglec-8, for instance, has been identified as a therapeutic target for the treatment of eosinophil and mast cell disorders. A promising strategy to target Siglecs involves the use of liposomal nanoparticles with a multivalent display of Siglec ligands. A key challenge for this approach is the identification of a high affinity ligand for the target Siglec. Here, we report the development of a ligand of Siglec-8 and its closest murine functional orthologue Siglec-F that is capable of targeting liposomes to cells expressing Siglec-8 or -F. A glycan microarray library of synthetic 9-N-sulfonyl sialoside analogs was screened to identify potential lead compounds The best ligand, 9-N-(2-naphthyl-sulfonyl)-Neu5Acα2-3-[6-O-sulfo]-Galβ1-4GlcNAc (6′-O-sulfo ^NSANeu5Ac) combined the lead 2-naphthyl sulfonyl C-9 substituent with the preferred sulfated scaffold. The ligand 6′-O-sulfo ^NSANeu5Ac was conjugated to lipids for display on liposomes to evaluate targeted delivery to cells. Targeted liposomes showed strong in vitro binding/uptake and selectivity to cells expressing Siglec-8 or -F and, when administered to mice, exhibit in vivo targeting to Siglec-F⁺ eosinophils.

Journal of the American Chemical Society published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C9H8ClNO3S, Synthetic Route of 166883-20-1.

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

Donaldson, Robert M. Jr. published the artcileUrinary excretion of indolic compounds in rats with intestinal pouches, Application In Synthesis of 2642-37-7, the publication is American Journal of Physiology (1961), 794-6, database is CAplus and MEDLINE.

The urinary excretion of indican and free and total indoleacetic acid is significantly increased in the rat in the presence of a localized area of intestinal stasis produced surgically by the creation of a pouch in the small intestine. Tryptamine, serotonin, and 5-hydroxyindoleacetic acid excretion in the urine is not altered. Intestinal stasis and bacterial activity within the pouch are responsible for the increased amounts of indican and indoleacetic acid in the urine.

American Journal of Physiology published new progress about 2642-37-7. 2642-37-7 belongs to indole-building-block, auxiliary class Indole,Salt,Sulfonate,Inhibitor,Inhibitor, name is Potassium 1H-indol-3-yl sulfate, and the molecular formula is C8H6KNO4S, Application In Synthesis of 2642-37-7.

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

Sadaie, Mahito published the artcileCell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition, COA of Formula: C19H21N3O3S, the publication is Molecular Biology of the Cell (2015), 26(17), 2971-2985, database is CAplus and MEDLINE.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides addnl. justification for AURKB as a cancer therapeutic target.

Molecular Biology of the Cell 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

Achab, Said published the artcileA short route to functionalized imidazo[4,5-c]carbazoles. Synthesis of the first example of the imidazo[4,5-c]β-carboline ring system, Product Details of C15H14BNO4S, the publication is Tetrahedron Letters (2001), 42(50), 8825-8828, database is CAplus.

A new synthetic route to the functionalized imidazo[4,5-c]carbazole I, via intramol. electrocyclization of the vinylimidazolylindole II is described. Thermally induced ring-closure of the (4-amino-5-imidazolyl)-3-indolecarboxylate III led to the previously unknown imidazo[4,5-c]-β-carboline ring system IV. These heterocycles were efficiently converted into analogs of both the marine cytotoxic agents grossularines-1 and -2 and the antimicrobial alkaloid eudistomin U.

Tetrahedron Letters published new progress about 149108-61-2. 149108-61-2 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Sulfamide,Benzene,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (1-tosyl-1H-Indol-3-yl)boronic acid, and the molecular formula is C15H14BNO4S, Product Details of C15H14BNO4S.

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

Shreevatsa, Bhargav published the artcileVirtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy, Application of 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, the publication is Molecules (2021), 26(22), 6863, database is CAplus and MEDLINE.

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous FAD-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaroms., and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chem. classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of -8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.

Molecules 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 C28H41N2P, Application of 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

Chen, Junjun published the artcileSelective and Cell-Active Inhibitors of the USP1/ UAF1 Deubiquitinase Complex Reverse Cisplatin Resistance in Non-small Cell Lung Cancer Cells, Related Products of indole-building-block, the publication is Chemistry & Biology (Cambridge, MA, United States) (2011), 18(11), 1390-1400, database is CAplus and MEDLINE.

Summary: Ubiquitin-specific proteases (USPs) have in recent years emerged as a promising therapeutic target class. We identified selective small-mol. inhibitors against a deubiquitinase complex, the human USP1/UAF1, through quant. high throughput screening (qHTS) of a collection of bioactive mols. The top inhibitors, pimozide and GW7647, inhibited USP1/UAF1 noncompetitively with a K _i of 0.5 and 0.7 μM, resp., and displayed selectivity against a number of deubiquitinases, deSUMOylase, and cysteine proteases. The USP1/UAF1 inhibitors act synergistically with cisplatin in inhibiting cisplatin-resistant non-small cell lung cancer (NSCLC) cell proliferation. USP1/UAF1 represents a promising target for drug intervention because of its involvement in translesion synthesis and Fanconi anemia pathway important for normal DNA damage response. Our results support USP1/UAF1 as a potential therapeutic target and provide an example of targeting the USP/WD40 repeat protein complex for inhibitor discovery.

Chemistry & Biology (Cambridge, MA, 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, 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

Pirovano, Valentina published the artcileGold-catalyzed synthesis of tetrahydrocarbazole derivatives through an intermolecular cycloaddition of vinyl indoles and N-allenamides, Safety of 5-Fluoro-1H-indole-2-carbaldehyde, the publication is Chemical Communications (Cambridge, United Kingdom) (2013), 49(34), 3594-3596, database is CAplus and MEDLINE.

A gold-catalyzed formal [4+2] cycloaddition of vinyl indoles and N-allenamides leading to tetrahydrocarbazoles is described. E.g., in presence of AuCl₃, [4+2] cycloaddition of vinyl indole (I) and N-allenamide (II) gave 83% tetrahydrocarbazole derivative (III). Moreover, new multicomponent reactions of vinyl indoles with two allene mols. are reported.

Chemical Communications (Cambridge, United Kingdom) published new progress about 220943-23-7. 220943-23-7 belongs to indole-building-block, auxiliary class Indole,Fluoride,Aldehyde, name is 5-Fluoro-1H-indole-2-carbaldehyde, and the molecular formula is C9H6FNO, Safety of 5-Fluoro-1H-indole-2-carbaldehyde.

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

Anastassiadis, Theonie published the artcileComprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity, Recommanded Product: SU6656, the publication is Nature Biotechnology (2011), 29(11), 1039-1045, database is CAplus and MEDLINE.

Small-mol. protein kinase inhibitors are widely used to elucidate cellular signaling pathways and are promising therapeutic agents. Owing to evolutionary conservation of the ATP-binding site, most kinase inhibitors that target this site promiscuously inhibit multiple kinases. Interpretation of experiments that use these compounds is confounded by a lack of data on the comprehensive kinase selectivity of most inhibitors. Here we used functional assays to profile the activity of 178 com. available kinase inhibitors against a panel of 300 recombinant protein kinases. Quant. anal. revealed complex and often unexpected interactions between protein kinases and kinase inhibitors, with a wide spectrum of promiscuity. Many off-target interactions occur with seemingly unrelated kinases, revealing how large-scale profiling can identify multitargeted inhibitors of specific, diverse kinases. The results have implications for drug development and provide a resource for selecting compounds to elucidate kinase function and for interpreting the results of experiments involving kinase inhibitors.

Nature Biotechnology 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

Vancraenenbroeck, Renee published the artcileIn silico, in vitro and cellular analysis with a kinome-wide inhibitor panel correlates cellular LRRK2 dephosphorylation to inhibitor activity on LRRK2, Synthetic Route of 330161-87-0, the publication is Frontiers in Molecular Neuroscience (2014), 00051, database is CAplus and MEDLINE.

A review. Leucine-rich repeat kinase 2 (LRRK2) is a complex, multidomain protein which is considered a valuable target for potential disease-modifying therapeutic strategies for Parkinson’s disease (PD). In mammalian cells and brain, LRRK2 is phosphorylated and treatment of cells with inhibitors of LRRK2 kinase activity can induce LRRK2 dephosphorylation at a cluster of serines including Ser910/935/955/973. It has been suggested that phosphorylation levels at these sites reflect LRRK2 kinase activity, however kinase-dead variants of LRRK2 or kinase activating variants do not display altered Ser935 phosphorylation levels compared to wild type. Furthermore, Ser910/935/955/973 are not autophosphorylation sites, therefore, it is unclear if inhibitor induced dephosphorylation depends on the activity of compounds on LRRK2 or on yet to be identified upstream kinases. Here we used a panel of 160 ATP competitive and cell permeable kinase inhibitors directed against all branches of the kinome and tested their activity on LRRK2 in vitro using a peptide-substrate-based kinase assay. In neuronal SH-SY5Y cells overexpressing LRRK2 we used compound-induced dephosphorylation of Ser935 as readout. In silico docking of selected compounds was performed using a modeled LRRK2 kinase structure. Receiver operating characteristic plots demonstrated that the obtained docking scores to the LRRK2 ATP binding site correlated with in vitro and cellular compound activity. We also found that in vitro potency showed a high degree of correlation to cellular compound induced LRRK2 dephosphorylation activity across multiple compound classes. Therefore, acute LRRK2 dephosphorylation at Ser935 in inhibitor treated cells involves a strong component of inhibitor activity on LRRK2 itself, without excluding a role for upstream kinases. Understanding the regulation of LRRK2 phosphorylation by kinase inhibitors aids our understanding of LRRK2 signaling and may lead to development of new classes of LRRK2 kinase inhibitors.

Frontiers in Molecular 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 C10H15ClO3S, 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

Jin, Shengfei published the artcileVisible Light-Induced Borylation of C-O, C-N, and C-X Bonds, Name: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Journal of the American Chemical Society (2020), 142(3), 1603-1613, database is CAplus and MEDLINE.

Aryl phosphates, arylammonium salts and aryl halides were borylated with B₂pin₂ in photochem. substitution reaction catalyzed by phenothiazines, yielding aryl pinacolboranes and aryltrifluoroborates. Boronic acids are centrally important functional motifs and synthetic precursors. Visible light-induced borylation may provide access to structurally diverse boronates, but a broadly efficient photocatalytic borylation method that can effect borylation of a wide range of substrates, including strong C-O bonds, remains elusive. Herein, we report a general, metal-free visible light-induced photocatalytic borylation platform that enables borylation of electron-rich derivatives of phenols and anilines, chloroarenes, as well as other haloarenes. The reaction exhibits excellent functional group tolerance, as demonstrated by the borylation of a range of structurally complex substrates. Remarkably, the reaction is catalyzed by phenothiazine, a simple organic photocatalyst with MW < 200 that mediates the previously unachievable visible light-induced single electron reduction of phenol derivatives with reduction potentials as neg. as approx. – 3 V vs. SCE by a proton-coupled electron transfer mechanism. Mechanistic studies point to the crucial role of the photocatalyst-base interaction.

Journal of the American Chemical Society published new progress about 642494-36-8. 642494-36-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Indole,Boronate Esters,Boronic acid and ester, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H18BNO2, Name: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole.

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