ZM 241385

Pricing Availability   Qty
说明: Potent and highly selective A2A antagonist
化学名: 4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol
纯度: ≥99% (HPLC)
说明书
引用文献 (108)
评论 (1)
文献 (1)

生物活性 for ZM 241385

ZM 241385 is a potent and highly selective A2A adenosine antagonist, with a pA2 of 9.02 for A2A receptors in guinea pig cardiac vasculature and fold selectivities of 1000, 91 and 500,000 over A1, A2B and A3 sites respectively. Active in vivo. ZM 241385 suppresses the ERK1/2 pathway in human squamous carcinoma cells.

许可信息

Sold with the permission of AstraZeneca UK Ltd.

化合物库 for ZM 241385

ZM 241385 is also offered as part of the Tocriscreen 2.0 Max. 了解 Tocris 化合物库的更多信息。

技术数据 for ZM 241385

分子量 337.34
公式 C16H15N7O2
储存 Store at RT
纯度 ≥99% (HPLC)
CAS Number 139180-30-6
PubChem ID 176407
InChI Key PWTBZOIUWZOPFT-UHFFFAOYSA-N
Smiles NC1=NC(NCCC2=CC=C(O)C=C2)=NC2=NC(=NN12)C1=CC=CO1

上方提供的技术数据仅供参考。批次相关数据请参见分析证书。

Tocris products are intended for laboratory research use only, unless stated otherwise.

溶解性数据 for ZM 241385

溶剂 最高浓度 mg/mL 最高浓度 mM
溶解性
ethanol 1.69 5
DMSO 33.73 100

制备储备液 for ZM 241385

以下数据基于产品分子量 337.34。 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

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浓度/溶剂体积/质量 1 mg 5 mg 10 mg
1 mM 2.96 mL 14.82 mL 29.64 mL
5 mM 0.59 mL 2.96 mL 5.93 mL
10 mM 0.3 mL 1.48 mL 2.96 mL
50 mM 0.06 mL 0.3 mL 0.59 mL

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产品说明书 for ZM 241385

分析证书/产品说明书
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参考文献 for ZM 241385

参考文献是支持产品生物活性的出版物。

Keddie et al (1996) In vivo characterisation of ZM 241385, a selective adenosine A2A receptor antagonist. Eur.J.Pharmacol. 301 107 PMID: 8773453

Poucher et al (1995) The in vitro pharmacology of ZM 241385, a potent, non-xanthine, A2a selective adenosine receptor antagonist. Br.J.Pharmacol. 115 1096 PMID: 7582508

Poucher et al (1996) Pharmacodynamics of ZM 241385, a potent A2a adenosine receptor antagonist, after enteric administration in rat, cat and dog. J.Pharm.Pharmacol. 48 601 PMID: 8832494

Palani et al (2018) Toll-like receptor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases ½. Oncotarget 9 6814 PMID: 29467931


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关键词: ZM 241385, ZM 241385 supplier, Potent, selective, A2A, antagonist, Receptors, adenosines, ZM241385, AstraZeneca, Adenosine, ERK, 1036, Tocris Bioscience

108 篇 ZM 241385 的引用文献

引用文献是使用了 Tocris 产品的出版物。 ZM 241385 的部分引用包括:

Caiazzo et al (2016) Adenosine signalling mediates the anti-inflammatory effects of the COX-2 inhibitor nimesulide. Biochem.Pharmacol. 112 72 PMID: 27188793

Mediavilla-Varela et al (2013) Antagonism of adenosine A2A receptor expressed by lung adenocarcinoma tumor cells and cancer associated fibroblasts inhibits their growth. Neuropsychopharmacology 14 860 PMID: 23917542

Fernández-Dueñas et al (2013) DA D(2) receptor-mediated modulation of adenosine A(2A) receptor agonist binding within the A(2A)R/D(2)R oligomer framework. Oncoimmunology 63 42 PMID: 23619397

Jastrzebska et al (2013) Expression of mammalian G protein-coupled receptors in Caenorhabditis elegans. J Neurochem 520 239 PMID: 23332703

Hein et al (2013) Cellular signalling pathways mediating dilation of porcine pial arterioles to adenosine A2A receptor activation. Blood 99 156 PMID: 23539502

Shi et al (2008) Interaction of mechanisms involving epoxyeicosatrienoic acids, adenosine receptors, and metabotropic glutamate receptors in neurovascular coupling in rat whisker barrel cortex. J Cereb Blood Flow Metab 28 111 PMID: 17519974

Monticone et al (2022) Targeting the Cbl-b-Notch1 axis as a novel immunotherapeutic strategy to boost CD8+ T-cell responses. Front.Immunol. 13 987298 PMID: 36090975

Oliveira et al (2015) Deficits in endogenous adenosine formation by ecto-5'-nucleotidase/CD73 impair neuromuscular transmission and immune competence in experimental autoimmune myasthenia gravis. Mediators Inflamm 2015 460610 PMID: 25691808

Perez-Aso et al (2015) Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors. Arthritis Res Ther 17 249 PMID: 26370839

Stoddart et al (2015) Application of BRET to monitor ligand binding to GPCRs. Nat Methods 12 661 PMID: 26030448

Chiodi et al (2014) Cocaine-induced changes of synaptic transmission in the striatum are modulated by adenosine A2A receptors and involve the tyrosine phosphatase STEP. Neuropsychopharmacology 39 569 PMID: 23989619

Ahsan and Mehal (2014) Activation of adenosine receptor A2A increases HSC proliferation and inhibits death and senescence by down-regulation of p53 and Rb. Front Pharmacol 5 69 PMID: 24782773

Perígolo-Vicente et al (2014) IL-6, A1 and A2aR: a crosstalk that modulates BDNF and induces neuroprotection. Biochem Biophys Res Commun 449 477 PMID: 24845382

Welihinda and Amento et al (2014) Positive allosteric modulation of the adenosine A2a receptor attenuates inflammation. J Inflamm (Lond) 11 37 PMID: 25473378

Ruiz-García et al (2011) Cooperation of adenosine with macrophage Toll-4 receptor agonists leads to increased glycolytic flux through the enhanced expression of PFKFB3 gene. J Biol Chem 286 19247 PMID: 21464136

Zhukov et al (2011) Biophysical mapping of the adenosine A2A receptor. J Med Chem 54 4312 PMID: 21661720

Jin et al (2011) Paeoniflorin suppresses the expression of intercellular adhesion molecule-1 (ICAM-1) in endotoxin-treated human monocytic cells. Br J Pharmacol 164 694 PMID: 21542832

Singh et al (2008) Large-scale functional expression of WT and truncated human adenosine A2A receptor in Pichia pastoris bioreactor cultures. Eur J Immunol 7 28 PMID: 18847468

Fernandez et al (2008) Pharmacological blockade of A2A receptors prevents dermal fibrosis in a model of elevated tissue adenosine. J Pharmacol Exp Ther 172 1675 PMID: 18467695

Garcia et al (2008) Adenosine A2A receptor activation and macrophage-mediated experimental glomerulonephritis. Am J Physiol Regul Integr Comp Physiol 22 445 PMID: 17898087

Liou et al (2008) Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. PLoS One 49 5526 PMID: 18641283

Csóka et al (2008) Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function. FASEB J 22 3491 PMID: 18625677

Ruby et al (2014) Adenosinergic regulation of striatal clock gene expression and ethanol intake during constant light. Kidney Int 39 2432 PMID: 24755889

Nam et al (2013) Adenosine transporter ENT1 regulates the acquisition of goal-directed behavior and ethanol drinking through A2A receptor in the dorsomedial striatum. J Neurosci 33 4329 PMID: 23467349

He et al (2013) Adenosine regulates bone metabolism via A1, A2A, and A2B receptors in bone marrow cells from normal humans and patients with multiple myeloma. FASEB J 27 3446 PMID: 23682121

Kiebala and Maggirwar (2011) Ibudilast, a pharmacologic phosphodiesterase inhibitor, prevents human immunodeficiency virus-1 Tat-mediated activation of microglial cells. PLoS One 6 e18633 PMID: 21494611

Tozzi et al (2011) The distinct role of medium spiny neurons and cholinergic interneurons in the D2/A2A receptor interaction in the striatum: implications for Parkinson's disease. J Neurosci 31 1850 PMID: 21289195

Ohta et al (2009) A2A adenosine receptor may allow expansion of T cells lacking effector functions in extracellular adenosine-rich microenvironments. Cardiovasc Res 183 5487 PMID: 19843934

Yu et al (2009) Effect of ventilation pressure on alveolar fluid clearance and β-agonist responses in mice. Cancer Biol Ther 297 L785 PMID: 19684202

Guibert et al (1998) Dependence of P2-nucleotide receptor agonist-mediated endothelium-independent relaxation on ectonucleotidase activity and A2A-receptors in rat portal vein. Br J Pharmacol 123 1732 PMID: 9605582

Haynes et al (1998) A1 and A2 adenosine receptor modulation of contractility in the cauda epididymis of the guinea-pig. Br J Pharmacol 125 570 PMID: 9806342

Nakav et al Anti-inflammatory preconditioning by agonists of adenosine A1 receptor. J Immunol 3 e2107 PMID: 18461129

Hegde et al (2015) Critical Role of Mast Cells and Peroxisome Proliferator-Activated Receptor γ in the Induction of Myeloid-Derived Suppressor Cells by Marijuana Cannabidiol In Vivo. J Immunol 194 5211 PMID: 25917103

Takedachi et al (2012) CD73-generated adenosine promotes osteoblast differentiation. J Cell Physiol 227 2622 PMID: 21882189

Lindquist (2012) Adenosine receptor activation is responsible for prolonged depression of synaptic transmission after spreading depolarization in brain slices. Neuroscience 223 365 PMID: 22864185

Maeda and Koos (2009) Adenosine A1 and A2a receptors modulate Insemia, glycemia, and lactatemia in fetal sheep. Proc Natl Acad Sci U S A 296 R693 PMID: 19118101

Alam et al (2009) A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence. Mucosal Immunol 2 232 PMID: 19262506

Wilson et al (2009) The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells. J Immunol 182 4616 PMID: 19342636

Clark et al (2009) Adenosine-evoked hyperpolarization of retinal ganglion cells is mediated by G-protein-coupled inwardly rectifying K+ and small conductance Ca2+-activated K+ channel activation. J Neurosci 29 11237 PMID: 19741130

Epperson et al (2009) Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts. Am J Physiol Cell Physiol 296 C1171 PMID: 19244482

Wen and Knowles (2003) Extracellular ATP and adenosine induce cell apoptosis of human hepatoma Li-7A cells via the A3 adenosine receptor. Br J Pharmacol 140 1009 PMID: 14530217

Nishi et al (2003) Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Br J Pharmacol 100 1322 PMID: 12538871

Dall'Igna et al (2003) Neuroprotection by caffeine and adenosine A2A receptor blockade of β-amyloid neurotoxicity. PLoS One 138 1207 PMID: 12711619

Brito et al (2002) Adenosine A(2A) receptors in portal hypertension: their role in the abnormal response to adenosine of the cranial mesenteric artery in rabbits. J Neurosci 135 1324 PMID: 11877342

Hirsh and Silinsky (2002) Inhibition of spontaneous acetylcholine secretion by 2-chloroadenosine as revealed by a protein kinase inhibitor at the mouse neuromuscular junction. Br J Pharmacol 135 1897 PMID: 11959792

Koshiba et al (2002) 2-Chloroadenosine but not adenosine induces apoptosis in rheumatoid fibroblasts independently of cell surface adenosine receptor signalling. Br J Pharmacol 135 1477 PMID: 11906961

Lee and Chao (2001) Activation of Trk neurotrophin receptors in the absence of neurotrophins. Purinergic Signal 98 3555 PMID: 11248116

Avila et al (2001) A(1)-, A(2A)- and A(3)-subtype adenosine receptors modulate intraocular pressure in the mouse. Br J Pharmacol 134 241 PMID: 11564641

Nieri et al (2001) Adenosine-mediated hypotension in in vivo guinea-pig: receptors involved and role of NO. Br J Pharmacol 134 745 PMID: 11606314

Slesinger (2001) British Pharmacological Society Meeting. 18-21 December 2000, University of Birmingham. Abstracts. Br J Pharmacol 133 Suppl 1P PMID: 11403025

Haynes (2000) A(2A) adenosine receptor mediated potassium channel activation in rat epididymal smooth muscle. Br J Pharmacol 130 685 PMID: 10821799

Anderson et al (2000) Accelerated resequestration of cytosolic calcium and suppression of the pro-inflammatory activities of human neutrophils by CGS 21680 in vitro. Br J Pharmacol 130 717 PMID: 10864876

Latini et al (1999) Effect of A2A adenosine receptor stimulation and antagonism on synaptic depression induced by in vitro ischaemia in rat hippocampal slices. Br J Pharmacol 128 1035 PMID: 10556941

Hernandez et al (1999) A2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission. Br J Pharmacol 126 969 PMID: 10193777

Jenabian et al (2013) Regulatory T cells negatively affect IL-2 production of effector T cells through CD39/adenosine pathway in HIV infection. PLoS Pathog 9 e1003319 PMID: 23658513

Waickman et al (2012) Enhancement of tumor immunotherapy by deletion of the A2A adenosine receptor. Cancer Immunol Immunother 61 917 PMID: 22116345

Golembiowska and Dziubina (2012) The effect of adenosine A(2A) receptor antagonists on hydroxyl radical, DA, and glutamate in the striatum of rats with altered function of VMAT2. Neurotox Res 22 150 PMID: 22407500

Carlström et al (2010) Adenosine A(2) receptors modulate tubuloglomerular feedback. Am J Physiol Renal Physiol 299 F412 PMID: 20519378

Pugliese et al (2009) The adenosine A2A receptor antagonist ZM241385 enhances neuronal survival after oxygen-glucose deprivation in rat CA1 hippocampal slices. Br J Pharmacol 157 818 PMID: 19422385

Germack and Dickenson (2004) Characterization of ERK1/2 signalling pathways induced by adenosine receptor subtypes in newborn rat cardiomyocytes. Br J Pharmacol 141 329 PMID: 14751870

Yip (2004) Role of adenosine A2A receptor in the regulation of gastric somatostatin release. J Pharmacol Exp Ther 309 804 PMID: 14742743

Fresco et al (2004) Facilitation of noradrenaline release by activation of adenosine A(2A) receptors triggers both phospholipase C and adenylate cyclase pathways in rat tail artery. Cardiovasc Res 63 739 PMID: 15306230

Nuccio et al (2019) Adenosine A2A receptor stimulation restores cell functions and differentiation in Niemann-Pick type C-like oligodendrocytes. Sci Rep 9 9782 PMID: 31278313

Ryzhov et al (2019) Number of Circulating CD 73-Expressing Lymphocytes Correlates With Survival After Cardiac Arrest. J Am Heart Assoc 8 e010874 PMID: 31237169

Cunha et al (2015) Creatine, similarly to KA, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation. Biochem J 11 215 PMID: 25702084

Kohno et al (2015) Anti-inflammatory effects of adenosine N1-oxide. Biosci Rep 12 2 PMID: 25632271

Jamshad et al (2015) G-protein coupled receptor solubilization and purification for biophysical analysis and functional studies, in the total absence of detergent. Mol Cell Biol 35 PMID: 25720391

Tosolini et al (2015) Human monocyte recognition of adenosine-based cyclic dinucleotides unveils the A2a Gαs protein-coupled receptor tonic inhibition of mitochondrially induced cell death. Am J Physiol Lung Cell Mol Physiol 35 479 PMID: 25384972

Paisansathan et al (2010) Interactions between adenosine and K+ channel-related pathways in the coupling of somatosensory activation and pial arteriolar dilation. Am J Physiol Heart Circ Physiol 299 H2009 PMID: 20889844

Bertarelli et al (2006) Characterization of human and rodent native and recombinant adenosine A(2B) receptors by radioligand binding studies. Purinergic Signal 2 559 PMID: 18404493

Newman (2005) Calcium increases in retinal glial cells evoked by light-induced neuronal activity. Blood 25 5502 PMID: 15944378

Kornerup et al (2005) Pharmacological characterisation of the adenosine receptor mediating increased ion transport in the mouse isolated trachea and the effect of allergen challenge. Br J Pharmacol 144 1011 PMID: 15685200

Jacobson et al (2005) A neoceptor approach to unraveling microscopic interactions between the human A2A adenosine receptor and its agonists. Chem Biol 12 237 PMID: 15734651

Erdmann et al (2005) Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo. J Pharmacol Exp Ther 105 4707 PMID: 15746085

Murphree et al (2005) Lipopolysaccharide rapidly modifies adenosine receptor transcripts in murine and human macrophages: role of NF-κB in A(2A) adenosine receptor induction. Methods Enzymol 391 575 PMID: 16022683

Liu et al (2016) Activation of Adenosine 2A receptor inhibits neutrophil apoptosis in an autophagy-dependent manner in mice with systemic inflammatory response syndrome. Scientific Reports 6 33614 PMID: 27647162

Mediero et al (2016) Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine-dependent mechanism. FASEB J. PMID: 27511945

Stoddart et al (2012) Fragment screening at adenosine-A(3) receptors in living cells using a fluorescence-based binding assay. Chem Biol 19 1105 PMID: 22999879

Tozzi et al (2012) A2A adenosine receptor antagonism enhances synaptic and motor effects of cocaine via CB1 cannabinoid receptor activation. PLoS One 7 e38312 PMID: 22715379

Kinsey et al (2012) Autocrine adenosine signaling promotes regulatory T cell-mediated renal protection. J Am Soc Nephrol 23 1528 PMID: 22835488

Suzuki et al (2012) CD8+CD45RA+CCR7+FOXP3+ T cells with immunosuppressive properties: a novel subset of inducible human regulatory T cells. J Immunol 189 2118 PMID: 22821963

Lee et al (2012) When cytokinin, a plant hormone, meets the adenosine A2A receptor: a novel neuroprotectant and lead for treating neurodegenerative disorders? PLoS One 7 e38865 PMID: 22719969

Mediero et al (2012) Adenosine A2A receptor activation prevents wear particle-induced osteolysis. Sci Transl Med 4 135ra65 PMID: 22623741

Williams and Cronstein (2012) The effect of A(2A) adenosine receptor activation on C-C chemokine receptor 7 expression in human THP1 macrophages during inflammation. Inflammation 35 614 PMID: 21739164

Gebremedhin et al (2010) Adenosine can mediate its actions through generation of reactive oxygen species. J Cereb Blood Flow Metab 30 1777 PMID: 20531463

Gazoni et al (2010) Activation of A1, A2A, or A3 adenosine receptors attenuates lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg 140 440 PMID: 20398911

Mandapathil et al (2010) Generation and accumulation of immunosuppressive adenosine by human CD4+CD25highFOXP3+ regulatory T cells. J Biol Chem 285 7176 PMID: 19858205

Himer et al (2010) Adenosine A2A receptor activation protects CD4+ T lymphocytes against activation-induced cell death. FASEB J 24 2631 PMID: 20371613

Bingham et al (2010) A2A adenosine receptor stimulation decreases foam cell formation by enhancing ABCA1-dependent cholesterol efflux. J Leukoc Biol 87 683 PMID: 20089670

Riccioni et al (2010) Adenosine A(2A) Receptor Binding Profile of Two Antagonists, ST1535 and KW6002: Consideration on the Presence of Atypical Adenosine A(2A) Binding Sites. Front Psychiatry 1 22 PMID: 21423433

Lappas et al (2006) Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation. Mol Biol Cell 203 2639 PMID: 17088433

Zhang et al (2006) Adenosine A2a receptors induce heterologous desensitization of chemokine receptors. Microb Cell Fact 108 38 PMID: 16522819

Ge et al (2006) Cl-IB-MECA [2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide] reduces ischemia/reperfusion injury in mice by activating the A3 adenosine receptor. J Inflamm (Lond) 319 1200 PMID: 16985166

Chan et al (2006) Adenosine A(2A) receptors play a role in the pathogenesis of hepatic cirrhosis. Br J Pharmacol 148 1144 PMID: 16783407

Sassi et al (2014) Cardiac myocyte-secreted cAMP exerts paracrine action via adenosine receptor activation. J Clin Invest 124 5385 PMID: 25401477

Fernández-Dueñas et al (2012) Molecular determinants of A2AR-D2R allosterism: role of the intracellular loop 3 of the D2R. Invest Ophthalmol Vis Sci 123 373 PMID: 22924752

Mandapathil et al (2012) CD26 expression and adenosine deaminase activity in regulatory T cells (Treg) and CD4(+) T effector cells in patients with head and neck squamous cell carcinoma. FASEB J 1 659 PMID: 22934258

Lee et al (2012) Polyphenol (-)-epigallocatechin gallate-induced cardioprotection may attenuate ischemia-reperfusion injury through adenosine receptor activation: a preliminary study. Biomol Ther (Seoul) 63 340 PMID: 23115687

Jeon et al (2012) Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A Receptor Stimulation: A Possible Role in Neuroprotection. Neurochem Int 20 27 PMID: 24116271

Garcia et al (2011) Adenosine A(2A) receptor activation prevents progressive kidney fibrosis in a model of immune-associated chronic inflammation. Proc Natl Acad Sci U S A 80 378 PMID: 21508927

Long et al (2010) Adenosine receptor regulation of coronary blood flow in Ossabaw miniature swine. J Exp Med 335 781 PMID: 20855445

Wang et al (2010) Static magnetic field exposure reproduces cellular effects of the Parkinson's disease drug candidate ZM241385. Korean J Anesthesiol 5 e13883 PMID: 21079735

Nowak et al (2010) The A2aR adenosine receptor controls cytokine production in iNKT cells. Am J Pathol 40 682 PMID: 20039304

Ramanathan et al (2007) Synergistic up-regulation of vascular endothelial growth factor (VEGF) expression in macrophages by adenosine A2A receptor agonists and endotoxin involves transcriptional regulation via the hypoxia response element in the VEGF promoter. Br J Pharmacol 18 14 PMID: 17065555

Hirata et al (2018) CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine. Cell Stem Cell 22 445 PMID: 29456159

Palani et al (2018) Toll-like receptor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases ½. Oncotarget 9 6814 PMID: 29467931

Ng (2018) Inhibition of cytokine-mediated JNK signalling by purinergic P2Y11 receptors, a novel protective mechanism in endothelial cells. Cell Signal 51 59 PMID: 30076967

Wakisaka et al (2017) An Adenosine Receptor for Olfaction in Fish. Curr Biol 27 1437 PMID: 28502661


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Mouse solenocytes.
By Tahmineh Safaie on 10/09/2020
分析类型: Ex Vivo
种属: Mouse
细胞系/组织: solenocytes

Mouse solenocytes were activated with antiCD3/28 and treated with 5 uM of ZM241385 in presence or absence of CGS21680. After 24 hours the supernatant was collected, and IFN-gamma was measured by ELISA.

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