.cp_wz table {border-top: 1px solid #ccc; border-left: 1px solid #ccc; } .cp_wz table td {border-right: 1px solid #ccc; borda inferior: 1px sólido #ccc; preenchimento: 5px 0px 0px 5px;} .cp_wz tabela th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; preenchimento: 5px 0px 0px 5px;} \ n Peso molecular: 228,21 A decitabina é um potente inibidor da metilação do DNA com IC50 de 438 nM e 4,38 nM em células HL-60 e KG1a, respectivamente. \ n Atividade biológica A decitabina inibe o crescimento celular em uma forma dependente da dose e do tempo com IC50 de aproximadamente 438 nM e 43,8 nM por 72 horas e 96 horas de exposição em células leucêmicas HL-60 e KG1a, respectivamente. Um estudo recente mostra que a Decitabina exibe alta atividade antiproliferativa e pró-apoptótica contra o linfoma anaplásico de células grandes (ALCL) e inibe a captação de [3H] -timidina nas células KARPAS-299 com EC50 de 0,49 μM. Em um modelo de xenoenxerto murino ALK + KARPAS-299, a decitabina na dose de 2,5 mg / kg causa aumento da apoptose e redução da proliferação de células tumorais, e também resulta na desmetilação do supressor tumoral p16INK4A. Ensaio de cinase de protocolo (apenas para referência): [1]
DNA synthesis assay
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The rate of DNA synthesis is measured by the incorporation of radioactive thymidine into DNA. HL-60 and KG1a cells are suspended in 2 mL RPMI medium containing 10% fetal serum in 6-well (35 mm diameter) dishes and incubated with different concentrations of corresponding drugs for 48 hours (drugs are added simultaneously). At 48 hours, 0.5 μCi [3H] thymidine (6.7 Ci/mmol) is added to each well and incubated for an additional 24 hours. The cells are placed on GF/C glass fiber filters (2.4 cm diameter), washed with cold 0.9% NaCl, 5% cold trichloroacetic acid and ethanol. The filters containing the DNA are then dried, placed in EcoLite scintillation liquid (ICN) and the radioactivity measured using Beckman LS 6000IC scintillation counter. The IC50 is defined as the concentration of drug that inhibits 50% of the DNA synthesis of the leukemic cell lines from the dose–response curve.
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Ensaio de células: [1]
Cell lines
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HL-60 and KG1a
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Concentrations
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0-500 nM
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Incubation Time
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96 hours
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Method
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For the growth inhibition assay, cells in log phase are placed in 5 mL of medium. Different concentrations of Decitabine are added to the medium simultaneously. Cell counts are performed at the indicated times using a model ZM Coulter Counter. The concentration that produces 50% inhibition of growth (IC50) is determined from the growth curves of the drug treated leukemic cell lines.
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Estudo Animal: [2]
Animal Models
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KARPAS-299 human cells are inoculated subcutaneously into the right and left flanks of the mice.
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Formulation
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Decitabine is dissolved in sterile PBS .
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Dosages
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≤2.5 mg/kg
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Administration
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Administered via i.p.
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Solubility
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30% propylene glycol, 5% Tween 80, 65% D5W,
30 mg/mL
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* 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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Conversão de diferentes modelos de animais com base em BSA (valor com base em dados das diretrizes preliminares da FDA)
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 exemplo, para modificar a dose de resveratrol usada para um camundongo (22,4 mg / kg) para uma dose baseada na BSA para um rato, multiplique 22,4 mg / kg pelo fator Km para um camundongo e, em seguida, divida pelo fator Km para um rato. Este cálculo resulta em uma dose equivalente de rato para o resveratrol de 11,2 mg / kg.
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 Informação Química
Molecular Weight (MW)
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228.21
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Formula
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C8H12N4O4
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CAS No.
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2353-33-5
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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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Deoxycytidine
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Solubility (25°C) *
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In vitro
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DMSO
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45 mg/mL
(197.18 mM)
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Water
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10 mg/mL
(43.81 mM)
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Ethanol
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<1 mg/mL
(
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In vivo
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30% propylene glycol, 5% Tween 80, 65% D5W
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30 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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4-amino-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1,3,5-triazin-2(1H)-one
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Grupo de Produto : Epigenética > Inibidor de DNA Metiltransferase