Home / PI 3-Kinase Inhibitors / LY 294002 hydrochloride

LY 294002 hydrochloride

Catalog #: 1130
115 Citations Datasheet / COA / SDS
Catalog # Availability Size / Price Qty
1130/5
1130/25
LY 294002 hydrochloride | CAS No. 934389-88-5 | PI 3-Kinase Inhibitors
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Description: Prototypical PI 3-kinase inhibitor; also inhibits other kinases

Chemical Name: 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one hydrochloride

Purity: ≥99%

Product Details
Citations (115)
Supplemental Products
Reviews
Biological Activity Technical Data Additional Information Background Product Datasheets Calculators

Biological Activity

LY 294002 hydrochloride is a prototypical PI 3-kinase inhibitor (IC 50 values are 0.31, 0.73, 1.06 and 6.60 μM for PI 3-Kβ, PI 3-Kα, PI 3-Kδ and PI 3-Kγ respectively). Also inhibits other kinases including, CK2, mTOR, PLK1, PIM1 and PIM3. Inhibits proliferation and induces apoptosis in human colon cancer cells in vitro and in vivo. Suppresses proliferation of mESCs. Inhibits autophagic sequestration in rat hepatocytes. Negative Control also available.

Technical Data

M.Wt:
343.81
Formula:
C19H17NO3.HCl
Solubility:
Soluble to 25 mM in DMSO
Purity:
≥99%
Storage:
Store at RT
CAS No:
934389-88-5

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Additional Information

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Citations for LY 294002 hydrochloride

The citations listed below are publications that use Tocris products. Selected citations for LY 294002 hydrochloride include:

115 Citations: Showing 1 - 10

  1. Extracorporeal shock waves protect cardiomyocytes from DOX-induced cardiomyopathy by upregulating survivin via the integrin-ILK-Akt-Sp1/p53 axis.
    Authors: Lee Et al.
    Sci Rep  2019;9:12149
  2. The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling.
    Authors: Oh Et al.
    J Ginseng Res  2019;43:421
  3. Dual RXR motifs regulate nerve growth factor-mediated intracellular retention of the delta opioid receptor.
    Authors: Shiwarski Et al.
    Mol Biol Cell  2019;30:680
  4. Human vascular cell responses to the circulating bone hormone osteocalcin.
    Authors: Millar Et al.
    J Cell Physiol  2019;234:21039
  5. The Protective Effect of Ins. on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities.
    Authors: Zakharova Et al.
    Int J Mol Sci  2019;20
  6. Characterization of the brain penetrant neuropeptide Y Y2 receptor antagonist SF-11.
    Authors: Domin Et al.
    ACS Chem Neurosci  2019;10:3454
  7. Intracellular emetic signaling evoked by the L-type Ca2+ channel agonist FPL64176 in the least shrew (Cryptotis parva).
    Authors: Zhong Et al.
    Eur J Pharmacol  2018;834:157
  8. The homozygous CX3CR1-M280 mutation impairs human monocyte survival.
    Authors: Collar Et al.
    JCI Insight  2018;3
  9. PI3Kδ activates E2F1 synthesis in response to mRNA translation stress.
    Authors: Gnanasundram Et al.
    Nat Commun  2017;8:2103
  10. A pluripotent stem cell-based model for post-implantation human amniotic sac development.
    Authors: Shao
    Nat Commun  2017;8(1):208
  11. Structural and pharmacological basis for the induction of mitochondrial biogenesis by formo. but not clenbu.
    Authors: Cameron
    Sci Rep  2017;7(1):10578
  12. CFTR-mediated anion secretion across intestinal epithelium-like Caco-2 monolayer under PTH stimulation is dependent on intermediate conductance K+ channels.
    Authors: Jantarajit Et al.
    Am J Physiol Cell Physiol  2017;313:C118
  13. PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network.
    Authors: Shiwarski Et al.
    Mol Biol Cell  2017;28:2202
  14. Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity.
    Authors: Lei Et al.
    J Cell Biol  2017;216:2551
  15. Signaling Cascade Involved in Rapid Stimulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by dexameth.
    Authors: Bossmann Et al.
    Int J Mol Sci  2017;18
  16. Isolation and characterization of a new naturally immortalized human breast carcinoma cell line, KAIMRC1.
    Authors: Ali Et al.
    BMC Cancer  2017;17:803
  17. Negative regulation of ERK1/2 by PI3K is required for the protective effects of Pyropia yezoensis peptide against perfluorooctane sulfonate-induced endoplasmic reticulum stress.
    Authors: Oh Et al.
    Mol Med Rep  2017;15:2583
  18. Adenosine A3 receptor elicits chemoresistance mediated by multiple resistance-associated protein-1 in human glioblastoma stem-like cells.
    Authors: Torres Et al.
    Oncotarget  2016;7:67373
  19. miR-382 targeting PTEN-Akt axis promotes liver regeneration.
    Authors: Bei Et al.
    Elife  2016;7:1584
  20. The GABAB positive allosteric modulators CGP7930 and GS39783 stimulate ERK1/2 signalling in cellslacking functional GABAB receptors
    Authors: Olianas Et al.
    European Journal of Pharmacology  2016;794:135
  21. Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit.
    Authors: Hatzold Et al.
    Elife  2016;5
  22. Cannabinoid receptor agonist WIN55,212-2 and fatty acid amide hydrolase inhibitor URB597 may protect against cognitive impairment in rats of chronic cerebral hypoperfusion via PI3K/AKT signaling
    Authors: Shao-Hua Su Et al.
    Behavioural Brain Research  2016;313:334
  23. Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells
    Authors: Mou Et al.
    Cell: Stem Cell  2016;19:217
  24. Pyrrolidine dithiocarbamate activates the Nrf2 pathway in astrocytes.
    Authors: Liddell Et al.
    J Neuroinflammation  2016;13:49
  25. Poly(I:C) increases the expression of mPGES-1 and COX-2 in rat primary microglia.
    Authors: Oliveira Et al.
    Int J Mol Med  2016;13:11
  26. Progesterone receptor membrane component-1 regulates hepcidin biosynthesis.
    Authors: Li Et al.
    J Clin Invest  2016;126:389
  27. Up-Regulated Expression of LAMP2 and Autophagy Activity during Neuroendocrine Differentiation of Prostate Cancer LNCaP Cells
    Authors: Morell Et al.
    PLoS One  2016;11:e0162977
  28. Phosphoinositide-3-Kinase Is the Primary Mediator of Phosphoinositide-Dependent Inhibition in Mammalian Olfactory Receptor Neurons.
    Authors: Ukhanov Et al.
    Front Cell Neurosci  2016;10:97
  29. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo.
    Authors: Najm Et al.
    Int J Cancer  2015;522:216
  30. Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron.
    Authors: Lindström Et al.
    J Biomed Sci  2015;3:e04000
  31. The thymoquinone-induced production of reactive oxygen species promotes dedifferentiation through the ERK pathway and inflammation through the p38 and PI3K pathways in rabbit articular chondrocytes.
    Authors: Yu and Kim
    Alcohol Clin Exp Res  2015;35:325
  32. Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest.
    Authors: Long Et al.
    J Cell Physiol  2015;230:1929
  33. Dimeric dipeptide mimetics of the nerve growth factor Loop 4 and Loop 1 activate TRKA with different patterns of intracellular signal transduction.
    Authors: Gudasheva Et al.
    Nature  2015;22:106
  34. PI3K Phosphorylation Is Linked to Improved Electrical Excitability in an In Vitro Engineered Heart Tissue Disease Model System.
    Authors: Kana Et al.
    Tissue Eng Part A  2015;21:2379
  35. Neuregulin 1 signalling modulates mGluR1 function in mesencephalic dopaminergic neurons.
    Authors: Ledonne Et al.
    Mol Psychiatry  2015;20:959
  36. A novel mechanism for cytoprotection against hypoxic injury: δ-opioid receptor-mediated increase in Nrf2 translocation.
    Authors: Cao Et al.
    Oncotarget  2015;172:1869
  37. SDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II.
    Authors: Choi Et al.
    PLoS One  2015;136:E219
  38. An in vitro model of latency and reactivation of varicella zoster virus in human stem cell-derived neurons.
    Authors: Markus Et al.
    PLoS Pathog  2015;11:e1004885
  39. Upregulation of Nicotinic Acetylcholine Receptor α4+β2 through a Ligand-Independent PI3Kβ Mechanism That Is Enhanced by TNFα and the Jak2/p38Mapk Pathways.
    Authors: Rogers and Gahring
    J Neuroinflammation  2015;10:e0143319
  40. Glucocorticoids Distinctively Modulate the CFTR Channel with Possible Implications in Lung Development and Transition into Extrauterine Life.
    Authors: Laube Et al.
    PLoS One  2015;10:e0124833
  41. Palladin mediates stiffness-induced fibroblast activation in the tumor microenvironment.
    Authors: McLane and Ligon
    Biophys J  2015;109:249
  42. ER-α36-mediated rapid estrogen signaling positively regulates ER-positive breast cancer stem/progenitor cells.
    Authors: Deng Et al.
    BMC Cancer  2014;9:e88034
  43. Angiogenic growth factors augment K-Cl cotransporter expression in erythroid cells via hypoxia-inducible factor-1α.
    Authors: Gonsalves Et al.
    Am J Hematol  2014;89:273
  44. Non-cell-autonomous mechanism of activity-dependent neurotransmitter switching.
    Authors: Guemez-Gamboa Et al.
    Neuron  2014;82:1004
  45. Interaction of mTOR and Erk1/2 signaling to regulate oligodendrocyte differentiation.
    Authors: Dai Et al.
    Glia  2014;62:2096
  46. Rapid elevation of sodium transport through Ins is mediated by AKT in alveolar cells.
    Authors: Mattes Et al.
    Physiol Rep  2014;2:e00269
  47. Decrease of PKB/Akt Phosphorylation is Partially Mediated by SAPK/JNK Activation in Serum-free L6 Myoblasts Starved with Low Glucose.
    Authors: Kim Et al.
    J Phys Ther Sci  2014;26:1757
  48. δ-Opioid receptors up-regulate excitatory amino acid transporters in mouse astrocytes.
    Authors: Liang Et al.
    J Exp Bot  2014;171:5417
  49. BDNF-endocannabinoid interactions at neocortical inhibitory synapses require phospholipase C signaling.
    Authors: Zhao
    J Neurophysiol  2014;111:1008
  50. Characterisation of AmphiAmR11, an amphioxus (Branchiostoma floridae) D2-DA-like G protein-coupled receptor.
    Authors: Bayliss and Evans
    PLoS One  2013;8:e80833
  51. Acetate supplementation induces growth arrest of NG2/PDGFRα-positive oligodendroglioma-derived tumor-initiating cells.
    Authors: Long Et al.
    PLoS One  2013;8:e80714
  52. Curcumin suppresses migration and proliferation of Hep3B hepatocarcinoma cells through inhibition of the Wnt signaling pathway.
    Authors: Kim Et al.
    Mol Med Rep  2013;8:282
  53. ATP-competitive mTOR kinase inhibitors delay plant growth by triggering early differentiation of meristematic cells but no developmental patterning change.
    Authors: Montané and Menand
    Neuroscience  2013;64:4361
  54. PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of post-traumatic epilepsy.
    Authors: Berdichevsky Et al.
    J Neurosci  2013;33:9056
  55. Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats.
    Authors: Faria Et al.
    Am J Physiol Endocrinol Metab  2013;305:E230
  56. Cellular Ins resistance disrupts leptin-mediated control of neuronal signaling and transcription.
    Authors: Nazarians-Armavil Et al.
    Mol Endocrinol  2013;27:990
  57. Label-free integrative pharmacology on-target of opioid ligands at the opioid receptor family.
    Authors: Morse Et al.
    BMC Pharmacol Toxicol  2013;14:17
  58. Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade.
    Authors: Yung Et al.
    J Steroid Biochem Mol Biol  2013;13:327
  59. PI 3-kinase independent role for AKT in F-actin regulation during outer segment phagocytosis by RPE cells.
    Authors: Bulloj Et al.
    Exp Eye Res  2013;113:9
  60. Melatonin induces transcriptional regulation of Bim by FoxO3a in HepG2 cells.
    Authors: Carbajo-Pescador Et al.
    Br J Cancer  2013;108:442
  61. Ceramide 1-phosphate stimulates proliferation of C2C12 myoblasts.
    Authors: Gangoiti Et al.
    Biochimie  2012;94:597
  62. Fucoidan from seaweed Fucus vesiculosus inhibits migration and invasion of human lung cancer cell via PI3K-Akt-mTOR pathways.
    Authors: Lee Et al.
    PLoS One  2012;7:e50624
  63. PPARδ activation protects endothelial function in diabetic mice.
    Authors: Tian Et al.
    Diabetes  2012;61:3285
  64. PI3K/Akt signaling pathway in the basolateral amygdala mediates the rapid antidepressant-like effects of trefoil factor 3.
    Authors: Shi Et al.
    Neuropsychopharmacology  2012;37:2671
  65. Nucleus accumbens mGluR5-associated signaling regulates binge alcohol drinking under drinking-in-the-dark procedures.
    Authors: Cozzoli Et al.
    Cancer Res  2012;36:1623
  66. Cervical spinal erythropoietin induces phrenic motor facilitation via extracellular signal-regulated protein kinase and Akt signaling.
    Authors: Dale Et al.
    J Neurosci  2012;32:5973
  67. Curcumin inhibits HCV replication by induction of heme oxygenase-1 and suppression of AKT.
    Authors: Chen Et al.
    Int J Mol Med  2012;30:1021
  68. A screen for regulators of survival of motor neuron protein levels.
    Authors: Makhortova Et al.
    Nat Chem Biol  2011;7:544
  69. Ligand-directed functional selectivity at the mu opioid receptor revealed by label-free integrative pharmacology on-target.
    Authors: Morse Et al.
    PLoS One  2011;6:e25643
  70. Astragaloside IV stimulates angiogenesis and increases hypoxia-inducible factor-1α accumulation via phosphatidylinositol 3-kinase/Akt pathway.
    Authors: Zhang Et al.
    J Pharmacol Exp Ther  2011;338:485
  71. The canonical nuclear factor-κB pathway regulates cell survival in a developmental model of spinal cord motoneurons.
    Authors: Mincheva Et al.
    J Neurosci  2011;31:6493
  72. JNK suppression is essential for 17β-OE inhibits prostaglandin E2-Induced uPA and MMP-9 expressions and cell migration in human LoVo colon cancer cells.
    Authors: Hsu Et al.
    J Med Food  2011;18:61
  73. A positive cross-regulation of HER2 and ER-α36 controls ALDH1 positive breast cancer cells.
    Authors: Kang Et al.
    J Pharmacol Exp Ther  2011;127:262
  74. Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by α7 and β2* nicotinic stimulation.
    Authors: Barrio Et al.
    Toxicol Sci  2011;123:193
  75. TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles.
    Authors: Li Et al.
    Environ Health Perspect  2011;119:784
  76. Cortical overexpression of neuronal calcium sensor-1 induces functional plasticity in spinal cord following unilateral pyramidal tract injury in rat.
    Authors: Yip Et al.
    PLoS Biol  2010;8:e1000399
  77. Extranuclear estrogen receptors mediate the neuroprotective effects of estrogen in the rat hippocampus.
    Authors: Yang Et al.
    PLoS One  2010;5:e9851
  78. Pharmacological and genetic accumulation of hypoxia-inducible factor-1alpha enhances excitatory synaptic transmission in hippocampal neurons through the production of vascular endothelial growth factor.
    Authors: Huang Et al.
    J Neurosci  2010;30:6080
  79. Leptin regulates AMPA receptor trafficking via PTEN inhibition.
    Authors: Moult Et al.
    J Neurosci  2010;30:4088
  80. Mechano-transduction in osteoblastic cells involves strain-regulated estrogen receptor alpha-mediated control of Ins-like growth factor (IGF) I receptor sensitivity to Ambient IGF, leading to phosphatidylinositol 3-kinase/AKT-dependent Wnt/LRP5 receptor-i
    Authors: Sunters Et al.
    J Biol Chem  2010;285:8743
  81. miR-155 and its star-form partner miR-155* cooperatively regulate type I IF. production by human plasmacytoid dendritic cells.
    Authors: Zhou Et al.
    Blood  2010;116:5885
  82. Level of G protein-coupled receptor kinase-2 determines myocardial ischemia/reperfusion injury via pro- and anti-apoptotic mechanisms.
    Authors: Brinks Et al.
    J Cell Sci  2010;107:1140
  83. Optimal experimental design for parameter estimation of a cell signaling model.
    Authors: Bandara Et al.
    PLoS Comput Biol  2009;5:e1000558
  84. FcεRI-induced activation by low antigen concentrations results in nuclear signals in the absence of degranulation.
    Authors: Grodzki Et al.
    Circ Res  2009;46:2539
  85. Activation of glycogen synthase kinase-3 β is required for hyperDA and D2 receptor-mediated inhibition of synaptic NMDA receptor function in the rat prefrontal cortex.
    Authors: Li Et al.
    J Biol Chem  2009;29:15551
  86. Regulation of p53 expression, phosphorylation and subcellular localization by a G-protein-coupled receptor.
    Authors: Solyakov Et al.
    Oncogene  2009;28:3619
  87. PLZF is a regulator of homeostatic and cytokine-induced myeloid development.
    Authors: Doulatov Et al.
    Genes Dev  2009;23:2076
  88. Glycogen synthase kinase-3 and Omi/HtrA2 induce annexin A2 cleavage followed by cell cycle inhibition and apoptosis.
    Authors: Wang Et al.
    Mol Biol Cell  2009;20:4153
  89. Ethanol augments RANTES/CCL5 expression in rat liver sinusoidal endothelial cells and human endothelial cells via activation of NF-kappa B, HIF-1 alpha, and AP-1.
    Authors: Yeligar Et al.
    J Immunol  2009;183:5964
  90. Ethanol-induced expression of ET-1 and ET-BR in liver sinusoidal endothelial cells and human endothelial cells involves hypoxia-inducible factor-1alpha and microrNA-199.
    Authors: Yeligar Et al.
    J Immunol  2009;183:5232
  91. c-jun controls the ability of IL-12 to induce IL-10 production from human memory CD4+ T cells.
    Authors: Garcia Et al.
    J Immunol  2009;183:4475
  92. C5a mediates peripheral blood neutrophil dysfunction in critically ill patients.
    Authors: Morris Et al.
    Am J Respir Crit Care Med  2009;180:19
  93. Soy phytoestrogens are neuroprotective against stroke-like injury in vitro.
    Authors: Schreihofer and Redmond
    J Neurosci  2009;158:602
  94. Efficacy of signal pathway inhibitors alone and in combination with cisp. varies between human non-small cell lung cancer lines.
    Authors: Kilic Et al.
    J.Surg.Res.  2009;154:9
  95. Blockade of estrogen receptor signaling inhibits growth and migration of medulloblastoma.
    Authors: Belcher Et al.
    Endocrinology  2009;150:1112
  96. Mechanisms underlying fibronectin-induced up-regulation of P2X4R expression in microglia: distinct roles of PI3K-Akt and MEK-ERK signalling pathways.
    Authors: Tsuda Et al.
    J Cell Mol Med  2009;13:3251
  97. Inulin increases glucose transport in C2C12 myotubes and HepG2 cells via activation of AMP-activated protein kinase and phosphatidylinositol 3-kinase pathways.
    Authors: Yun Et al.
    PLoS One  2009;12:1023
  98. Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells.
    Authors: Cho Et al.
    J Vet Sci  2009;10:23
  99. PI3 kinase/Akt activation mediates estrogen and IGF-1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson's disease.
    Authors: Quesada Et al.
    Dev Neurobiol  2008;68:632
  100. Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells.
    Authors: Jung Et al.
    Carcinogenesis  2008;29:713
  101. Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions.
    Authors: Pezet Et al.
    J Neurosci  2008;28:4261
  102. Temporal profiling of changes in phosphatidylinositol 4,5-bisphosphate, inositol 1,4,5-trisphosphate and diacylglycerol allows comprehensive analysis of phospholipase C-initiated signalling in single neurons.
    Authors: Nelson Et al.
    J Neurochem  2008;107:602
  103. Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior.
    Authors: González-Maeso Et al.
    Exp Mol Med  2007;53:439
  104. Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase.
    Authors: Park Et al.
    Br J Pharmacol  2007;39:222
  105. cis-9,trans-11-conjugated linoleic acid down-regulates phorbol ester-induced NF-kappaB activation and subsequent COX-2 expression in hairless mouse skin by targeting IkappaB kinase and PI3K-Akt.
    Authors: Hwang Et al.
    Carcinogenesis  2007;28:363
  106. Regulation of DA transporter function and cell surface expression by D3 DA receptors.
    Authors: Zapata Et al.
    J Biol Chem  2007;282:35842
  107. IGF-I inhibition of apoptosis is associated with decreased expression of prostate apoptosis response-4.
    Authors: Chung Et al.
    J Endocrinol  2007;194:77
  108. Ins induces airway smooth muscle contraction.
    Authors: Schaafsma Et al.
    J Biomed Sci  2007;150:136
  109. PI-3-kinase-dependent membrane recruitment of centaurin-α2 is essential for its effect on ARF6-mediated actin cytoskeleton reorganisation.
    Authors: Venkateswarlu Et al.
    Neuron  2007;120:792
  110. Cyclin D1 is necessary for tamoxifen-induced cell cycle progression in human breast cancer cells.
    Authors: Kilker and Planas-Silva
    Mol Immunol  2006;66:11478
  111. Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus.
    Authors: Qiu Et al.
    Br J Pharmacol  2006;26:12943
  112. Ischemic preconditioning protects by activating prosurvival kinases at reperfusion.
    Authors: Hausenloy Et al.
    Am J Physiol Heart Circ Physiol  2005;288:H971
  113. Glucose deprivation increases mRNA stability of vascular endothelial growth factor through activation of AMP-activated protein kinase in DU145 prostate carcinoma.
    Authors: Yun Et al.
    J Neurosci  2005;280:9963
  114. LY 294002 inhibits adenosine receptor activation by a mechanism independent of effects on PI-3 kinase or casein kinase II.
    Authors: Searl and Silinsky
    Purinergic Signal  2005;1:389
  115. Phospholipase C-linked receptors regulate the ATP-sensitive potassium channel by means of phosphatidylinositol 4,5-bisphosphate metabolism.
    Authors: Xie Et al.
    Proc Natl Acad Sci U S A  1999;96:15292

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