Description du produit
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Poids moléculaire :
431.51 TAI-1 est un inhibiteur puissant et spécifique de Hec1, qui perturbe l'interaction entre les protéines Hec1-Nek2.
Activité biologique
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Description
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TAI-1 is a potent and specific Hec1 inhibitor, which disrupts Hec1-Nek2 protein interaction.
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Targets
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Hec1 [1]
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In vitro
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TAI-1 disrupts the binding of Nek2 to Hec1, which leads to degradation of Nek2 and chromosomal misalignment. TAI-1 shows strong growth inhibitory potency at nM levels across a broad spectrum of tumor cells, and produces synergistic activity with doxorubicin, topotecan and paclitaxel in leukemia, breast and liver cancer cells.
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In vivo
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TAI-1 (20 mg/kg i.v. or 150 mg/kg p.o.) causes significant tumor growth delay in Huh-7 model and modest tumor inhibition in Colo205 and MDA-MB-231 models.
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Features
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Protocole (uniquement pour référence) Dosage cellulaire : [1]
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Cell lines
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MDA-MB-231, MDA-MB-468, K562, HeLa, MCF7, HCC1954, A549, COLO205, U2OS, Huh-7, U937, HepG2, KG-1, PC3, BT474, MV4-11, RS4;11, MOLM-13, WI-38, HUVEC, RPTEC, HAoSMC, MDA-MB-453, T47D, ZR-75-1, ZR-75-30, MDA-MB-361, Hs578T, NCI-H520, Hep3B, PLC/PRF/5, RPMI8226, MOLT-4, N87, MES-SA/Dx5, NCI/ADR-RES, and K562R cells
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Concentrations
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~10 μM
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Incubation Time
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96 hours
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Method
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Cells are seeded in 96 well plates, incubated for 24 hours, compounds added and incubated for 96 hours. All testing points are tested in triplicate wells. Cell viability is determined by MTS assay using CellTiter 96® Aqueous Non-radioactive Cell Proliferation Assay system according to manufacturer`s instructions with MTS and PMS. Data retrieved from spectrophotometer are processed in Excel and GraphPad Prism 5 to calculate the concentration exhibiting 50% growth inhibition (GI50). All data represent the results of triplicate experiments.
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Étude animale : [1]
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Animal Models
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Female mice bearing Colo-205 or Huh-7 tumors; male mice bearing MDA-MB-231 tumors
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Formulation
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10% DMSO 25% PEG200; 5% DMSO, 10% Cremophor, 85% water
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Dosages
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20 mg/kg i.v./QDx28 cycles or 150 mg/kg p.o./BID/28 cycles in total
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Administration
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i.v. or p.o.
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Conversion de différents animaux modèles sur la base de la BSA (valeur basée sur les données des lignes directrices provisoires 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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Par exemple, pour modifier la dose de resvératrol utilisée pour une souris (22,4 mg/kg) à une dose basée sur la BSA pour un rat, multiplier 22,4 mg/kg par le facteur Km pour une souris puis diviser par le facteur Km pour un rat. Ce calcul donne une dose équivalente chez le rat pour le resvératrol 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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Informations chimiques
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Molecular Weight (MW)
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431.51
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Formula
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C24H21N3O3S
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CAS No.
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1334921-03-7
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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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N/A
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Chemical Name
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N-(4-(4-(4-methoxyphenoxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide
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Calculateur de molarité Calculateur de dilution Calculateur de poids moléculaire
Groupes de Produits : Signalisation cytosquelettique > Inhibiteur associé aux microtubules
