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Zosuquidar (LY335979) 3HCl 167465-36-3

Descrição do produto

.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: 636,99 Zosuquidar (LY335979) é um modulador potente de resistência a medicamentos mediada por glicoproteína P com Ki de 60 nM. Fase 3. \ n LY335979 inibe competitivamente a ligação de equilíbrio de [3H] vinblastina a Pgp, bloqueando a marcação de fotoafinidade de [3H] azidopina da Pgp em membranas plasmáticas CEM / VLB100. LY335979 sozinho mostra a citotoxicidade para linhas de células MDR e sensíveis a drogas com IC50 variando de 6 μM-16 μM e produz sua capacidade de reverter completamente a resistência dos oncolíticos (vinblastina, doxorrubicina ou etoposídeo) para as linhas de células MDR P388 / ADR , MCF7 / ADR, 2780AD ou UCLA-P3.003VLB na concentração de 0,1 e 0,5 μM. LY335979 restaura significativamente a sensibilidade ao medicamento em linhas celulares de leucemia que expressam P-gp, incluindo K562 / HHT40, K562 / HHT90, K562 / DOX e HL60 / DNR, e aumenta a citotoxicidade de antraciclinas (daunorrubicina, idarubicina, mitoxantrona) e gemgamicinumabilar em blastos de AML primários com P-gp ativa. Um artigo mais recente indica que LY335979 inibe completamente o transporte apicalmente dirigido de (Z) -endoxifeno nas células transduzidas ABCB1. \ n Protocolo (apenas para referência) Ensaio de cinase:
ATPase Assay P-Glycoprotein ATPase activity is measured by the liberation of inorganic phosphate from ATP. The assay is measured in a 96-well plate for 90 min at 37 °C. Membranes (8 μg-10 μg protein) are incubated in a total volume of 100 μL of buffer A containing 5 mM sodium azide, 1 mM ouabain, 1 mM EGTA, 3 mM ATP, an ATP regenerating system composed of 5 mM phosphoenolpyruvate, and 3.6 units/mL pyruvate kinase in the presence and absence of 1 mM sodium vanadate. Pgp-ATPase activity is defined as the vanadate-sensitive portion of the total ATPase activity. Plates are read 3 minutes after the addition of the detection solution. The absorbance is measured at 690 nm by a microtiter dish reader. A phosphate standard curve is used to calculate the μmol of phosphate formed. Samples are measured in triplicate.
Ensaio de células: [1]
Cell lines CEM/VLB100, P388/ADR, MCF7/ADR, 2780AD, and UCLA-P3.OO3VLB cells
Concentrations 0.05 μM to 5 μM
Incubation Time 72 hours
Method Cell viability is determined using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method. Cells are harvested during logarithmic growth phase, and seeded in 96-well plates. The cells are then cultured for 72 hours in the presence of oncolytics with or without modulators. MCF-7 and MCF-7/ADR cells are incubated 24 hours before the addition of the drug with and without the LY335979. LY335979 is prepared as 2 mM DMSO stocks and added to wells to give final concentrations ranging from 0.05 to 5 μM. After 72 hours, 20 μL of freshly prepared 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (5 mg/mL in Dulbecco's PBS) is added to each well and incubated for 4 hours in a 37 °C incubator containing 5% CO2. Cells are pelleted in a Sorvall RT6000B centrifuge, 70 μL of medium is carefully removed from each well, and 100 μL of 2-propanol/0.04 N HC1 is added. Cells are resuspended 5-10 times with a Multipipettor or until no particulate matter is visible. Plates are immediately read on a Titertek Multiskan MCC/340 microplate reader Flow Laboratories with a test wavelength of 570 nm and a reference wavelength of 630 nm. Controls are measured in quadruplicate and modulators are measured in duplicate. Cytotoxicity analyses are also performed using the CeliTiter 96 AQueous assay kit.
Conversão de diferentes modelos de animais com base em BSA (valor com base em dados das diretrizes preliminares da FDA)
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
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) × mouse Km(3) = 11.2 mg/kg
rat Km(6)
Informação Química
Molecular Weight (MW) 636.99
Formula

C32H31F2N3O2.3HCl

CAS No. 167465-36-3
Storage 3 years -20℃Powder
6 months-80℃in solvent (DMSO, water, etc.)
Synonyms
Solubility (25°C) * In vitro DMSO 100 mg/mL (156.98 mM)
Water 23 mg/mL (36.1 mM)
Ethanol <1 mg/mL (
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol 30 mg/mL

Chemical Name 1-Piperazineethanol, 4-[(1aα,6α,10bα)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]-α-[(5-quinolinyloxy)methyl]-,trihydrochloride
Calculadora de molaridade Calculadora de diluição Calculadora de peso molecular

Grupo de Produto : Sinalização Neuronal > Inibidor P-gp