印度恩杂鲁胺

产品描述

Enzalutamide (MDV 3100) is a non-steroidal androgen receptor (AR) antagonist (IC50: 36 nM in LNCaP prostate cells).

靶点活性

Androgen Receptor,36nM

实验溶液

2% DMSO+30% PEG300: 5 mg/mL

体外活性

Enzalutamide (MDV 3100) bound AR in castration-resistant LNCaP/AR human prostate cancer cells with 5-8 fold greater affinity than bicalutamide. MDV3100 antagonized induction of PSA and TMPRSS2 by the synthetic androgen R1881 in parental LNCaP cells. In the human prostate cancer cell line VCaP which has endogenous AR gene amplification, MDV3100 suppressed growth and induced apoptosis [1].

体内活性

Enzalutamide (10 mg/kg) induces great tumor regression in castrate male mice bearing LNCaP/AR xenografts [1]. After intravenous injection (Enzalutamide, 0.5-5 mg/kg), systemic clearance, volumes of distribution at steady state (Vss), and half-life (T½) remained unaltered as a function of dose, with values in the ranges of 80.4-86.3 mL/h/kg, 1020-1250 mL/kg, and 9.13-10.6 h, respectively. Following oral administration, absolute oral bioavailability was 89.7 % and not dose-dependent [2].

激酶实验

AR reporter assay: Enzalutamide is evaluated by an artificial AR response reporter system in a hormone refractory prostate cancer cell line. In this system, the prostate cancer LNCaP cells are engineered to stably express about 5-fold higher level of AR than endogenous level. The exogenous AR has similar properties to endogenous AR in that both are stabilized by a synthetic androgen R1881. The AR-over expressed cells are also engineered to stably incorporate an AR response reporter and the reporter activity of these cells shows features of hormone refractory prostate cancer. The antagonistic activity of Enzalutamide is tested in the presence of 100 pM of R1881. Engineered LNCaP cells are maintained in Iscove's medium containing 10% fetal bovine serum (FBS). Two days prior to Enzalutamide treatment, the cells are grown in Iscove's medium containing 10% charcoal-stripped FBS (CS-FBS) to deprive of androgens. The cells are split and grown in Iscove's medium containing 10% CS-FBS with 100 pM of R1881 and increasing concentrations of Enzalutamide. After two days of incubation, reporter activities are assayed.

细胞实验

For in vitro experiments, LNCaP or LNCaP/AR cells (10^4 cells/well) were androgen-starved by growth in media containing 5-10% charcoal-stripped serum for 3-5 days. Then the cells were challenged with various concentrations of R1881, bicalutamide, RD162 or MDV3100 in media containing 5-10% charcoal-stripped serum [1].

细胞系： LNCaP or LNCaP/AR cells

动物实验

In vivo tumorigenicity experiments were done by subcutaneous injection of 10^6 cells (100 uL in 50% Matrigel and 50% growth media) into the flanks of castrated male SCID mice. Daily gavage treatment (using a formulation of 1% carboxymethyl cellulose, 0.1% Tween-80, 5% DMSO) was initiated when tumor size reached ~100 mm3. Tumor size was measured weekly in three dimensions (l x w x d) with calipers. For in vivo luciferase imaging, d-luciferin substrate (100 μL, 15 mg/mL) was injected intraperitoneally. After 5 minutes, mice were anesthetized using isofluorane and imaged using a cooled charged-coupled device IVIS camera. Data were analyzed using Living Image 2.30 software [1].

动物模型：Castration-resistant LNCaP/HR xenografts in SCID mice

分子量

464.44

分子式

C21H16F4N4O2S

CAS

915087-33-1

溶解度

DMSO: 85 mg/mL (183 mM)

Ethanol: <1 mg/mL

（ < 1 mg/ml refers to the product slightly soluble or insoluble )

储存条件

store at -80°C

备注

For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.