Стауроспорин
Описание продукта
.cp_wz table {border-top: твердое тело 1px #ccc; border-left: твердое тело 1px #ccc; } .cp_wz таблица td {border-right: 1px solid #ccc; нижняя граница: сплошной 1px #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} \ n Молекулярный вес: \ n 466,53 Стауроспорин - мощный ингибитор PKC для PKCα, PKCγ и PKCη с IC50 2 нМ, 5 нМ и 4 нМ, менее эффективен в отношении PKCδ (20 нМ), PKCε (73 нМ) и мало активен по отношению к PKCζ (1086 нМ). Фаза 3. \ n Биологическая активность
Протокол (только для справки) Анализ киназы: [1]
Клеточный анализ: [3]
Исследование на животных: [8]
Конверсия различных модельных животных на основе BSA (значение на основе данных из проекта рекомендаций FDA)
Например, чтобы изменить дозу ресвератрола, используемую для мыши (22,4 мг / кг), на дозу, основанную на BSA для крысы, умножьте 22,4 мг / кг на коэффициент Km для мыши, а затем разделите на коэффициент Km для крыса. Этот расчет дает эквивалентную дозу ресвератрола для крыс 11,2 мг / кг.
\ n Информация о клинических испытаниях (данные с http://clinicaltrials.gov, обновлено 07.02.2015)
Химическая информация
Калькулятор молярности Калькулятор разведения Калькулятор молекулярной массы Область исследований Отзывы клиентов (3)
| Description | 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 | PKCα [1] | PKCη [1] | PKCγ [1] | PKCδ [1] | PKCε [1] | PKCζ [1] |
| IC50 | 2 nM | 4 nM | 5 nM | 20 nM | 73 nM | 1086 nM |
| In vitro | 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. | |||||
| In vivo | 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. | |||||
| Features |
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| Enzyme assay and binding assay | 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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| Cell lines | PC12 |
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| Concentrations | Dissolved in DMSO, final concentration 1 μM |
| Incubation Time | ~32 hours |
| Method |
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. |
| Animal Models | Male Mongolian gerbils or male Wistar rats subjected to transient ischemia |
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| Formulation | Dissolved in DMSO, and diluted in saline |
| Dosages | ~10 ng |
| Administration | Stereotaxically administered into the bilateral CAl subfield of the hippocampus |
| Species | Baboon | Dog | Monkey | Rabbit | Guinea pig | Rat | Hamster | Mouse |
| Weight (kg) | 12 | 10 | 3 | 1.8 | 0.4 | 0.15 | 0.08 | 0.02 |
| Body Surface Area (m2) | 0.6 | 0.5 | 0.24 | 0.15 | 0.05 | 0.025 | 0.02 | 0.007 |
| Km factor | 20 | 20 | 12 | 12 | 8 | 6 | 5 | 3 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
| Rat dose (mg/kg) = mouse dose (22.4 mg/kg) × | mouse Km(3) | = 11.2 mg/kg |
| rat Km(6) |
| NCT Number | Recruitment | Conditions |
Sponsor /Collaborators |
Start Date | Phases |
|---|---|---|---|---|---|
| NCT00301938 | Completed | 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 | National Cancer Institute (NCI) | December 2005 | Phase 1 |
| NCT00301938 | Completed | 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 | National Cancer Institute (NCI) | December 2005 | Phase 1 |
| NCT00098956 | Completed | Extensive Stage Small Cell Lung Cancer|Recurrent Small Cell Lung Cancer | National Cancer Institute (NCI) | January 2005 | Phase 2 |
| NCT00098956 | Completed | Extensive Stage Small Cell Lung Cancer|Recurrent Small Cell Lung Cancer | National Cancer Institute (NCI) | January 2005 | Phase 2 |
| NCT00082017 | Completed | Lymphoma, Large-Cell, Ki-1|Lymphoma, T-Cell | National Cancer Institute (NCI)|National Institutes of He ...more National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) | April 2004 | Phase 2 |
| Molecular Weight (MW) | 466.53 |
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| Formula |
C28H26N4O3 |
| CAS No. | 62996-74-1 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in solvent (DMSO, water, etc.) | |
| Synonyms | CGP 41251 |
| Solubility (25°C) * | In vitro | DMSO | 4 mg/mL (8.57 mM) |
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| Water | <1 mg/mL ( | ||
| Ethanol | <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 | 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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