.cp_wz tabla {borde superior: 1px sólido #ccc; borde izquierdo: 1px sólido #ccc; } .cp_wz table td {borde derecho: 1px sólido #ccc; borde inferior: 1px sólido #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; relleno: 5px 0px 0px 5px;} \ n Peso molecular: \ n 466.53 La estaurosporina es un potente inhibidor de PKC para PKCα, PKCγ y PKCη con IC50 de 2 nM, 5 nM y 4 nM, menos potente para PKCδ (20 nM), PKCε (73 nM) y poco activo para PKCζ (1086 nM). Fase 3. \ n Actividad biológica
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Description
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Staurosporine is a potent PKC inhibitor for PKCα, PKCγ and PKCη with IC50 of 2 nM, 5 nM and 4 nM, less potent to PKCδ (20 nM), PKCε (73 nM) and little active to PKCζ (1086 nM). Phase 3.
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Targets
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PKCα [1]
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PKCη [1]
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PKCγ [1]
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PKCδ [1]
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PKCε [1]
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PKCζ [1]
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IC50
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2 nM
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4 nM
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5 nM
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20 nM
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73 nM
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1086 nM
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In vitro
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Staurosporine, a microbial alkaloid, significantly inhibits protein kinase C from rat brain with IC50 of 2.7 nM. Staurosporine displays strong inhibitory effect against HeLa S3 cells with IC50 of 4 nM. [1] Staurosporine also inhibits a variety of other protein kinases, including PKA, PKG, phosphorylase kinase, S6 kinase, Myosin light chain kinase (MLCK), CAM PKII, cdc2, v-Src, Lyn, c-Fgr, and Syk with IC50 of 15 nM, 18 nM, 3 nM, 5 nM, 21 nM, 20 nM, 9 nM, 6 nM, 20 nM, 2 nM, and 16 nM, respectively. Staurosporine (1 μM) induces >90% apoptosis in PC12 cells. Consistently, Staurosporine treatment induces a rapid and prolonged elevation of intracellular free calcium levels [Ca2+]i, accumulation of mitochondrial reactive oxygen species (ROS), and subsequent mitochondrial dysfunction. [3] The apoptosis of MCF7 cells induced by Staurosporine can be enhanced by the expression of functional caspase-3 via caspase-8 activation and Bid cleavage. Staurosporine treatment at 1 μM only partially inhibits IL-3-stimulated Bcl2 phosphorylation but completely blocks PKC-mediated Bcl2 phosphorylation. Staurosporine induces apoptosis of human foreskin fibroblasts AG-1518, depending on the lysosomal cathepsins D mediated cytochrome c release and caspase activation. In addition to activating the classical mitochondrial apoptosis pathway, Staurosporine triggers a novel intrinsic apoptosis pathway, relying on the activation of caspase-9 in the absence of Apaf-1.
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In vivo
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In the gerbil and rat ischemia models, Staurosporine pretreatment (0.1-10 ng) before ischemia prevents neuronal damage in a dose-dependent manner, suggesting the involvement of PKC in CAl pyramidal cell death after ischemia.
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Features
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Protocolo (solo como referencia) Ensayo de quinasa: [1]
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Enzyme assay and binding assay
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Protein kinase C is assayed in a reaction mixture (0.25 mL) containing 5 μmol of Tris/HCl, pH 7.5, 2.5 μmol of magnesium acetate, 50 μg of histone II S, 20 μg of phosphatidylserine, 0.88 μg of diolein, 125 nmol of CaCl2, 1.25 nmol of [γ-32]ATP (5-10 × 104 cpm/nmol) and 5 μg of partially purified enzyme. The binding of [3H]PDBu to protein kinase C is determined: Reaction mixture (200 μL contained 4 μmo1 of Tris/malate, pH 6.8, 20 μmol of KCl, 30 nmol of CaC12, 20 μg of phosphatidylserine, 5 μg of partially purified protein kinase C, 0.5% (final concentration) of DMSO,10 pmol of [3H]PDBu (l-3 × 104 cpm/pmol) and 10 μL of various amounts of Staurosporine.
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Ensayo celular: [3]
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Cell lines
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PC12
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Concentrations
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Dissolved in DMSO, final concentration 1 μM
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Incubation Time
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~32 hours
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Method
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Cells are exposed to Staurosporine for ~32 hours. Cells are fixed in 4% paraformaldehyde and stained with the DNA-binding dye Hoechst 33342. Cells are visualized under epifluorescence illumination, and the percentage of apoptotic cells (cells with condensed and fragmented DNA) is determined.
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Estudio con animales: [8]
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Animal Models
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Male Mongolian gerbils or male Wistar rats subjected to transient ischemia
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Formulation
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Dissolved in DMSO, and diluted in saline
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Dosages
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~10 ng
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Administration
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Stereotaxically administered into the bilateral CAl subfield of the hippocampus
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Conversión de diferentes modelos de animales basados en BSA (valor basado en datos del Borrador de Directrices de la FDA)
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Species
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Baboon
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Dog
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Monkey
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Rabbit
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Guinea pig
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Rat
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Hamster
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Mouse
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Weight (kg)
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12
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10
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3
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1.8
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0.4
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0.15
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0.08
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0.02
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Body Surface Area (m2)
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0.6
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0.5
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0.24
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0.15
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0.05
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0.025
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0.02
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0.007
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Km factor
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20
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20
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12
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12
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8
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6
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5
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3
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Animal A (mg/kg) = Animal B (mg/kg) multiplied by
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Animal B Km
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Animal A Km
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Por ejemplo, para modificar la dosis de resveratrol utilizada para un ratón (22,4 mg / kg) a una dosis basada en el BSA para una rata, multiplique 22,4 mg / kg por el factor Km para un ratón y luego divida por el factor Km para una rata. Este cálculo da como resultado una dosis equivalente para ratas de resveratrol de 11,2 mg / kg.
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Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×
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mouse Km(3)
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= 11.2 mg/kg
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rat Km(6)
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\ n Información sobre ensayos clínicos (datos de http://clinicaltrials.gov, actualizados el 2015-02-07)
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NCT Number
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Recruitment
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Conditions
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Sponsor
/Collaborators
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Start Date
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Phases
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NCT00301938
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Completed
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Accelerated Phase Chronic Myelogenous Leukemia|Adult Acute Megakaryoblastic Leukemia (M7)|Adult Acute Minimally Differentiated Myeloid Leukemia (M0 ...more Accelerated Phase Chronic Myelogenous Leukemia|Adult Acute Megakaryoblastic Leukemia (M7)|Adult Acute Minimally Differentiated Myeloid Leukemia (M0)|Adult Acute Monoblastic Leukemia (M5a)|Adult Acute Monocytic Leukemia (M5b)|Adult Acute Myeloblastic Leukemia With Maturation (M2)|Adult Acute Myeloblastic Leukemia Without Maturation (M1)|Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities|Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)|Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)|Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)|Adult Acute Myelomonocytic Leukemia (M4)|Adult Acute Promyelocytic Leukemia (M3)|Adult Erythroleukemia (M6a)|Adult Pure Erythroid Leukemia (M6b)|Blastic Phase Chronic Myelogenous Leukemia|Myelodysplastic/Myeloproliferative Neoplasms|Previously Treated Myelodysplastic Syndromes|Recurrent Adult Acute Lymphoblastic Leukemia|Recurrent Adult Acute Myeloid Leukemia|Relapsing Chronic Myelogenous Leukemia|Secondary Acute Myeloid Leukemia|T-cell Adult Acute Lymphoblastic Leukemia|Untreated Adult Acute Lymphoblastic Leukemia|Untreated Adult Acute Myeloid Leukemia
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National Cancer Institute (NCI)
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December 2005
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Phase 1
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NCT00301938
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Completed
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Accelerated Phase Chronic Myelogenous Leukemia|Adult Acute Megakaryoblastic Leukemia (M7)|Adult Acute Minimally Differentiated Myeloid Leukemia (M0 ...more Accelerated Phase Chronic Myelogenous Leukemia|Adult Acute Megakaryoblastic Leukemia (M7)|Adult Acute Minimally Differentiated Myeloid Leukemia (M0)|Adult Acute Monoblastic Leukemia (M5a)|Adult Acute Monocytic Leukemia (M5b)|Adult Acute Myeloblastic Leukemia With Maturation (M2)|Adult Acute Myeloblastic Leukemia Without Maturation (M1)|Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities|Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)|Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)|Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)|Adult Acute Myelomonocytic Leukemia (M4)|Adult Acute Promyelocytic Leukemia (M3)|Adult Erythroleukemia (M6a)|Adult Pure Erythroid Leukemia (M6b)|Blastic Phase Chronic Myelogenous Leukemia|Myelodysplastic/Myeloproliferative Neoplasms|Previously Treated Myelodysplastic Syndromes|Recurrent Adult Acute Lymphoblastic Leukemia|Recurrent Adult Acute Myeloid Leukemia|Relapsing Chronic Myelogenous Leukemia|Secondary Acute Myeloid Leukemia|T-cell Adult Acute Lymphoblastic Leukemia|Untreated Adult Acute Lymphoblastic Leukemia|Untreated Adult Acute Myeloid Leukemia
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National Cancer Institute (NCI)
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December 2005
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Phase 1
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NCT00098956
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Completed
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Extensive Stage Small Cell Lung Cancer|Recurrent Small Cell Lung Cancer
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National Cancer Institute (NCI)
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January 2005
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Phase 2
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NCT00098956
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Completed
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Extensive Stage Small Cell Lung Cancer|Recurrent Small Cell Lung Cancer
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National Cancer Institute (NCI)
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January 2005
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Phase 2
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NCT00082017
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Completed
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Lymphoma, Large-Cell, Ki-1|Lymphoma, T-Cell
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National Cancer Institute (NCI)|National Institutes of He ...more National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
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April 2004
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Phase 2
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Información química
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Molecular Weight (MW)
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466.53
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Formula
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C28H26N4O3
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CAS No.
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62996-74-1
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Storage
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3 years -20℃Powder
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6 months-80℃in solvent (DMSO, water, etc.)
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Synonyms
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CGP 41251
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Solubility (25°C) *
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In vitro
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DMSO
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4 mg/mL
(8.57 mM)
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Water
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<1 mg/mL
(
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Ethanol
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<1 mg/mL
(
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* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
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Chemical Name
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9,13-Epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-1-one, 2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-11-(methylamino)-, [9S-(9α,10β,11β,13α)]-
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular Área de investigación Reseñas de clientes (3)
Click to enlarge
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Intracellular concentration of HSF1-phosphoserine 326, total HSF1, S6 kinase-phosphothreonine-389, total S6 kinase and β-actin, without or with heat shock in HeLa cells pretreated with mTOR inhibitors rapamycin (30 nM) and KU0063794 (2 uM) and kinase inhibitor staurosporine (100 nM) for 2 hr. Relative levels of HSF1-phosphoserine 326 in cells after the various treatments were determined by densitometric analysis of X-ray films, normalized to untreated cells (lane 1), and are indicated below the representation of the immunoblots.
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Calificación \ n Fuente PLoS One 2012 7 (6), e39679. Estaurosporina comprada de Selleck Method Western blot Cell Lines Células HeLa Concentraciones 100 nM Tiempo de incubación 2 h Resultados Se examinó el efecto sobre la fosforilación de HSF1-S326 de fármacos que han demostrado inhibir la actividad de mTOR, incluyendo rapamicina, KUOO6379 y estaurosporina. El choque térmico condujo a la fosforilación de HSF1 en S326. La estaurosporina inhibió la activación inducida por estrés de la fosforilación de HSF1-S326 mientras que abolió la fosforilación en T389 de la quinasa ribosómica S6, un sustrato bien caracterizado para mTOR. La inhibición de la fosforilación de HSF1 en S326 por rapamicina sugiere que este sitio en HSF1 es un objetivo para el complejo TORC1.
Click to enlarge
Calificación \ n Fuente J Biomol Screen 2013 18 (4), 388-99. Estaurosporina comprada en Selleck Método Ensayos de unión y actividad Líneas celulares Células de insectos infectadas con baculovirus Concentraciones 0.001-10000 uM Tiempo de incubación \ n Resultados La estaurosporina se une preferentemente a npMEK1 en presencia de ATP.
Click to enlarge
Calificación \ n Fuente J Biomol Screen 2013 18 (4), 388-99. Estaurosporina comprada en el análisis de actividad enzimática del Método Selleck Líneas celulares \ n Concentraciones \ n Tiempo de incubación 75 min Resultados La estaurosporina, sunitinib, dasatinib y VX-680 pudieron inhibir completamente la actividad enzimática. Ver más citas de productos (5) El inhibidor de la proteína BET JQ1 atenúa el crecimiento tumoral de MCC amplificado por Myc in vivo [Shao Q, et al. Cancer Res 2014; 74 (23): 7090-102] PubMed: 25277525 La adhesión de leucocitos mediada por ICAM-1 es fundamental para la activación de LSP1 endotelial. [Hossain M, et al. Am J Physiol Cell Physiol 2013; 304 (9): C895-904] PubMed: 23447036 mTOR es esencial para la respuesta al estrés proteotóxico, la activación de HSF1 y la síntesis de proteínas de choque térmico. [Chou SD, et al. PLoS One 2012; 7 (6): e39679] PubMed: 22768106 Detección de inhibidores de quinasa alostérica por desplazamiento de sondas de sitio activo. [Lebakken CS, et al. J Biomol Screen 2012; 17 (6): 813-21] PubMed: 22453235 Desarrollo y validación de un ensayo de actividad de ATPasa intrínseca de alto rendimiento para el descubrimiento de inhibidores de MEKK2. [Ahmad S, et al. J Biomol Screen 2013; 18 (4): 388-99] PubMed: 23134735 Ver más clientes que compraron este artículo también compraron MK-2206 2HCl MK-2206 2HCl es un inhibidor altamente selectivo de Akt1 / 2/3 con IC50 de 8 nM / 12 nM / 65 nM, respectivamente; no se observaron actividades inhibidoras contra otras 250 proteína quinasas. Fase 2. Características: El primer inhibidor alostérico de molécula pequeña de Akt en entrar en desarrollo clínico. Vemurafenib (PLX4032, RG7204) Vemurafenib (PLX4032, RG7204) es un inhibidor nuevo y potente de B-RafV600E con IC50 de 31 nM. Características: Un inhibidor novedoso y potente de la oncoproteína B-RAFV600E. ABT-737 ABT-737 es un inhibidor mimético de BH3 de Bcl-xL, Bcl-2 y Bcl-w con CE50 de 78,7 nM, 30,3 nM y 197,8 nM, respectivamente; no se observó inhibición contra Mcl-1, Bcl-B o Bfl-1. Fase 2. Olaparib (AZD2281, Ku-0059436) Olaparib (AZD2281, KU0059436) es un inhibidor selectivo de PARP1 / 2 con IC50 de 5 nM / 1 nM, 300 veces menos eficaz contra tankyrase-1. Fase 3. Características: Un potente inhibidor de PARP (actualmente en ensayos clínicos en etapa tardía). Camptotecina La camptotecina es un inhibidor específico de la ADN topoisomerasa I (Topo I) con una CI50 de 0,68 μM. Fase 2. ABT-199 (GDC-0199) ABT-199 (GDC-0199) es un inhibidor selectivo de Bcl-2 con Ki de 4800 veces más selectivo que Bcl-xL y Bcl-w, y sin actividad para Mcl- 1. Fase 3. Características: Versión rediseñada de ABT-263 (Navitoclax). Soporte técnico y preguntas frecuentes Las respuestas a las preguntas que pueda tener se pueden encontrar en las instrucciones de manejo del inhibidor. Los temas incluyen cómo preparar soluciones madre, cómo almacenar inhibidores y cuestiones que requieren atención especial para ensayos basados en células y experimentos con animales. Grupos de Producto : Señalización citoesquelética > Inhibidor de PKC
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