Enzalutamide 是一种雄激素受体（AR）拮抗剂，可激活自噬，在 LNCaP 前列腺细胞中抑制 AR 的IC50值为 36 nM。

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

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].

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 (T?) 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].

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].

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].

915087-33-1

C21H16F4N4O2S

464.44

MDV3100;恩杂鲁胺

Ethanol:<1 mgml
DMSO:85 mg/mL (183 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years