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Search results for: ligand

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#32745892   2020/07/27 To Up

International real-world study of DLL3 expression in patients with small cell lung cancer.

Expression of the Notch-family ligand delta-like protein 3 (DLL3), a potential therapeutic target in small cell lung cancer (SCLC), has not been assessed in the real-world setting. To identify the real-world utility of DLL3 as an SCLC therapeutic target, we performed the largest retrospective international noninterventional study to date to evaluate DLL3 prevalence in SCLC patients.
Federico Rojo, Marcelo Corassa, Dimitrios Mavroudis, Aysim Büge Öz, Bonne Biesma, Luka Brcic, Patrick Pauwels, Verena Sailer, John Gosney, Darko Miljkovic, Carlos Hader, Meijing Wu, Todd Almarez, Frédérique Penault-Llorca

2869 related Products with: International real-world study of DLL3 expression in patients with small cell lung cancer.



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#32745819   2020/07/23 To Up

(±)-trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents: Synthesis, in vitro evaluation and SAR analysis.

Leishmaniasis, a neglected tropical disease caused by parasites of the genus Leishmania, causes a serious burden of disease around the world, represents a threat to the life of millions of people, and therefore is a major public health problem. More effective and non-toxic new treatments are required, especially for visceral leishmaniasis, the most severe form of the disease. On the backdrop that dihydrobenzofurans have previously shown antileishmanial activity, we present here the synthesis of a set of seventy trans-2-phenyl-2,3-dihydrobenzofurans and evaluation of their in vitro activity against Leishmania donovani as well as a discussion of structure-activity relationships. Compounds 8m-o and 8r displayed the highest potency (IC < 2 μmol/L) and interesting selectivity of the antileishmanial activity over cytotoxicity against mammalian cells (SI > 4.6). Nonetheless, structural optimization as further requirement was inferred from the high clearance of the most potent compound (8m) observed during determination in vitro of its metabolic stability. On the other hand, chiral separation of 8m and subsequent biological evaluation of its enantiomers demonstrated no effect of chirality on activity and cytotoxicity. Holistic analysis of in silico ADME-like properties and ligand efficiency metrics by a simple scoring function estimating druglikeness highlighted compounds 16c, 18 and 23 as promising candidates for further development. Overall, the potential of trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents was confirmed.
Freddy A Bernal, Marcel Gerhards, Marcel Kaiser, Bernhard Wünsch, Thomas J Schmidt

2747 related Products with: (±)-trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents: Synthesis, in vitro evaluation and SAR analysis.

1 kit(96 Wells)96 Tests50 assays1 kit(96 Wells)100 assays96 tests100.00 ul200

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#32745753   2020/07/22 To Up

Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches.

A series of diarylurea derivatives comprising 2,4-diarylpyrimidines were synthesized based on a combination of postulated molecular hybridization design and failed-ligands repurposing approaches, which enabled the discovery of novel potential antiproliferative agents. Towards credible biological evaluation, an in vitro anticancer activity assay was conducted employing a library of 60 cancer cell lines constituting nine panels representing blood, lung, colon, CNS, skin, ovary, renal, prostate, and breast cancers. The results revealed high effectiveness and broad-spectrum anticancer activity of compounds 4m and 4g. Five-dose assay of compounds 4m and 4g proved their high potency that surpassed that of four standard kinase inhibitors FDA-approved anticancer drugs against many cancer cells. Towards the identification of their molecular target, screening of kinase inhibitory profile employing a panel of 51 kinases involved in cancer revealed inhibition of several kinases from the platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) kinase family, which might mediate, at least in part, the antiproliferative activity. Molecular docking of 4g into the crystal structure of the Feline McDonough Sarcoma (FMS) kinase predicted that it binds to a pocket formed by the juxtamembrane domain, the catalytic loop, and the αE helix, thus stabilizing the inhibited conformation of the kinase. Flow cytometric study of the cytotoxic effects of compound 4g in A549 cells showed it induces dose- and time-dependent apoptotic events leading to cell death. Collectively, this work presents compound 4g as a potential broad-spectrum anticancer agent against multiple cancer types.
Ahmed Karam Farag, Ahmed H E Hassan, Kyung-Sook Chung, Jeong-Hun Lee, Hyo-Sun Gil, Kyung-Tae Lee, Eun Joo Roh

1806 related Products with: Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches.

25 mg50 ug20μg/vial100 ug/vial 6 ml Ready-to-use 5 G5 Modulatorsper vial1 kit 5 G

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#32745735   2020/07/15 To Up

Identification of novel scaffold using ligand and structure based approach targeting shikimate kinase.

Tuberculosis (TB) remains a major global health problem. It causes ill-health among millions of people each year and rank as the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus (HIV). Shikimate kinase is one of the major enzymes targeted for TB. Most approaches to overcome TB were based on synthesis and screening of a known compounds to obtain a few representatives with desired potency. In this study, we have applied a virtual screening approach which combines ligand- and structure-based approaches to screen a large library of compounds as a starting point for the identification of new scaffolds for the development of shikimate kinase inhibitors. The combined approach has identified 2 new scaffolds as potential inhibitors of shikimate kinase. To prove the approach, few of the molecules and their derivatives, a total of 17 compounds, were synthesized. The compounds were tested for biological activity and shows moderate activity against shikimate kinase. The shikimate kinase enzyme inhibition study reveals that the compounds showed inhibition (IC) at concentrations of 50 µg/mL (Compounds 21, 22, 24, 25, 26, 27, 30, 32, 34) and 25 µg/mL (14, 19, 23, 31, 33).
M B Rahul Reddy, Sivakumar Kullampalayam Krishnasamy, M K Kathiravan

2002 related Products with: Identification of novel scaffold using ligand and structure based approach targeting shikimate kinase.

100ug108 inhibitors250ul96T200ul100.00 ul100ug3 100.00 ug5 mg1 ml

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#32745715   2020/07/23 To Up

Synthesis of glucoside-based imidazolium salts for Pd-catalyzed cross-coupling reaction in water.

Sugar-based imidazolium salts (IMSs) represent an outstanding type of material making them eye-catching for a wide variety of applications. Herein, a series of glucoside-based IMSs (Glu-IMSs) combining glucoside and imidazolium head groups with different substituents were synthesized. The catalytic activities of these Glu-IMSs were evaluated by Pd-catalyzed Heck-Mizoroki and Suzuki-Miyaura reactions in water. Among them, the Glu-IMSs contain both -OH and NHCs coordination sites was found to be the most efficient ancillary ligand in comparison with other Glu-IMSs with just single NHCs coordination site. The HR-TEM analysis showed that the palladium nanoparticles stabilized by the Glu-IMSs with an average size of ~4.0 nm was formed in the reaction system, which may be act as an efficient real catalytic species. Under the optimized reaction conditions, a series of novel fluorine-cored organic small molecule functional materials were synthesized with favorable yields.
Zhonggao Zhou, Qian Xie, Xin Zhou, Yangyang Yuan, Yan Pan, Dongliang Lu, Ziyi Du, Jun Xue

1204 related Products with: Synthesis of glucoside-based imidazolium salts for Pd-catalyzed cross-coupling reaction in water.

100ug20000 Units 1 G500 Units10000 Units100ug2000 Units500 Units 1 G2000 Units1000 Units

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#32745361   2020/08/03 To Up

PhotoAffinity Bits: A photoaffinity-based fragment screening platform for efficient identification of protein ligands.

Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules are required to demonstrate that a ligand can have a disease-modifying effect. Currently, as tools are reported for only a fraction of the proteome, platforms for ligand discovery are essential to leverage insights from genomic analyses. Fragment screening offers an efficient approach to explore chemical space. We present a fragment screening platform, termed PhABits (PhotoAffinity Bits), which utilises a library of photoreactive fragments to covalently capture fragment-protein interactions. Hits can be profiled to determine potency and site of crosslinking, and subsequently developed as reporters in a competitive displacement assay to identify novel hit matter. We envision that the PhABits will be widely applicable to novel protein targets, identifying starting points in the development of therapeutics.
Emma K Grant, David J Fallon, Michael M Hann, Ken G M Fantom, Chad Quinn, Francesca Zappacosta, Roland S Annan, Chun-Wa Chung, Paul Bamborough, David P Dixon, Peter Stacey, David House, Vipulkumar K Patel, Nicholas C O Tomkinson, Jacob Bush

2470 related Products with: PhotoAffinity Bits: A photoaffinity-based fragment screening platform for efficient identification of protein ligands.

100ug0.1 mg100ug0.05mg0.1 mg10ìg100μg100 mg1 Set

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#32745326   // To Up

Tumor inhibition or tumor promotion? The duplicity of CXCR3 in cancer.

Tumor tissue includes cancer cells and normal stromal cells such as vascular endothelial cells, connective tissue cells (cancer associated fibroblast, mesenchymal stem cell), and immune cells (tumor-infiltrating lymphocytes or TIL, dendritic cells, eosinophils, basophils, mast cells, tumor-associated macrophages or TAM, myeloid-derived suppressor cells or MDSC). Anti-tumor activity is mainly mediated by infiltration of NK cells, Th1 and CD8 T cells, and correlates with expression of NK cell and T cell attracting chemokines. Nevertheless, cancer cells hijack tissue homeostasis through secretion of cytokines and chemokines that mediate not only the induction of an inflamed status that supports cancer cell survival and growth, but also the recruitment and/or activation of immune suppressive cells. CXCL9, CXCL10, and CXCL11 are known for their tumor-inhibiting properties, but their overexpression in several hematologic and solid tumors correlates with disease severity, suggesting a role in tumor promotion. The dichotomous nature of CXCR3 ligands activity mainly depends on several molecular mechanisms induced by cancer cells themselves able to divert immune responses and to alter the whole local environment. A deep understanding of the nature of such phenomenon may provide a rationale to build up a CXCR3/ligand axis targeting strategy. In this review, we will discuss the role of CXCR3 in cancer progression and in regulation of anti-tumor immune response and immunotherapy.
Eleonora Russo, Angela Santoni, Giovanni Bernardini

1587 related Products with: Tumor inhibition or tumor promotion? The duplicity of CXCR3 in cancer.



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#32745317   2020/08/03 To Up

Oxidative Addition of Water, Alcohols and Amines in Palladium Catalysis.

The homolytic cleavage of O-H and N-H or weak C-H bonds is a key elementary step in redox catalysis, yet thought to be unfeasible for palladium. In stark contrast, we report the room temperature and reversible oxidative addition of water, isopropanol, hexafluoroisopropanol, phenol, and aniline to a palladium(0) complex with a very labile pyridino ligand thus resembling pervasive N-heterocyclic carbene (NHC) palladium(II) pre-catalysts. We elucidate how the oxidative addition of protic solvents or adventitious water switches the chemoselectivity in palladium catalysis with alkynes through activation of the terminal C-H bond. Most salient, the homolytic activation of alcohols and amines allows for atom-efficient, additive-free cross coupling and transfer hydrogenation under mild reaction conditions with usually unreactive, yet desirable reagents including esters and bis(pinacolato)diboron.
Dominik Munz, Annette Grünwald, Frank W Heinemann

2079 related Products with: Oxidative Addition of Water, Alcohols and Amines in Palladium Catalysis.

100 ug 50 UG50μl20 1 L.50mg10 mgInhibitors500 tests

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#32745294   2020/08/03 To Up

Stack by stack: From the free cyclopentadienylgermanium cation via heterobi-metallic main-group sandwiches to main-group sandwich coordination polymers.

Heterobimetallic cationic sandwich complexes [M(µ-Cp)M'Cp]+ of Group 13 (M = Ga, In) and 14 (M' = Ge, Sn) were prepared as [WCA]- salts (WCA = Al(ORF)4; ORF = OC(CF3)3). Their molecular structures include free apical Ga or In atoms. The sandwich complexes form in reactions of [M(HMB)]+[WCA]- (HMB = C6Me6) with the free metallocenes M'Cp2. Their structures are related to known stannocene and stanno-cenium salts; the unprecedented germanium analogues - the free germanocenium cation [GeCp]+ and the respective triple-decker complex cation [CpGe(μ-Cp)GeCp]+ - are described herein. By variation of the reaction conditions, these sandwich complexes can be transformed to the mixed group 13/14 cationic coordination polymer [{In(HMB)(μ-SnCp2)}n][WCA]n. This polymeric chain motif was further successfully transferred to complexes containing FeCp2 as a bridging ligand in [{Ga/In(HMB)(μ-FeCp2)}n][WCA]n.
Marcel Schorpp, Ingo Krossing

2318 related Products with: Stack by stack: From the free cyclopentadienylgermanium cation via heterobi-metallic main-group sandwiches to main-group sandwich coordination polymers.

100 ug/vial100ug/vial200 100 100.00 ug50 ul200 100ug1 mL1 ml4 x 25 units

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#32745080   2020/08/03 To Up

CD154 inhibits death of T cells via a Cis interaction with the α5β1 integrin.

CD154 plays a major role in the pathogenesis of several autoimmune and inflammatory diseases. In addition to CD40, soluble CD154 (sCD154) binds to other receptors namely αIIbβ3, αMβ2, α5β1 and αvβ3 integrins. We have previously reported that binding of sCD154 to α5β1 integrin expressed on several human T cell lines is capable of inhibiting Fas-induced cell death. In the current study, we show that such effect of the sCD154/α5β1 interaction is not restricted to the cell death response induced by Fas but could also be exhibited toward other death signals such as TRAIL and TNF- α. We also demonstrate that sCD154 is capable of inhibiting Fas-mediated death of human activated T cells, more importantly of CD4+ than CD8+ T ones. Our data also show that membrane-bound CD154 and α5β1 integrin expressed on the surface of distinct cells failed to influence cell death responses. However, when membrane-bound CD154 and α5β1 are expressed on the surface of same cell, their interaction was capable of down regulating cell death. CD154 was shown to co-localize with the α5β1 integrin on the surface of these cells. These data strongly suggest a cis-type of interaction between CD154 and α5β1 when both are expressed on the same cell surface, rather than a trans-interaction which usually implicates the ligand and its receptor each expressed on the surface of a distinct cell. Taken together, these findings add to the list of roles through which CD154 is contributing to the pathogenesis of autoimmune-inflammatory diseases, i.e. by protecting T cells from death and enhancing their survival.
Meriem Bachsais, Suzanne Salti, Kossay Zaoui, Ghada S Hassan, Fawzi Aoudjit, Walid Mourad

1099 related Products with: CD154 inhibits death of T cells via a Cis interaction with the α5β1 integrin.

100 ug/vial1 Set100ug/vial1 Set1 Set1 Set100 Tests1 Set1 Set1 Set1 Set

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