product name Enzalutamide (MDV3100)
Description: Enzalutamide (also known as MDV3100) is a second-generation androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. Enzalutamide is an orally bioavailable, organic, non-steroidal small molecule with potential antineoplastic activity. It has higher affinity to the AR compared to the first-generation AR inhibitors. It acts by blocking the binding of androgens to the AR, AR nuclear translocation, and the association of the AR with DNA. The AR is a 919-amino acid member of the steroid receptor transcription factor superfamily with different domains including an N-terminal regulation domain.
References: Science. 2009 May 8;324(5928):787-90; Lancet. 2010 Apr 24;375(9724):1437-46.
464.44
Formula
C21H16F4N4O2S
CAS No.
915087-33-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 92 mg/mL (198.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
15% DMSO+85% PEG 300: 10mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394534
| In Vitro |
In vitro activity: Enzalutamide has greater affinity to AR than Bicalutamide does in a competition assay with 16β-[18F]fluoro-5α-DHT (18-FDHT) in castration-resistant LNCaP/AR cells (AR-overexpressing). While Enzalutamide shows no agonism in LNCaP/AR prostate cells. Enzalutamide antagonizes induction of prostate-specific antigen (PSA) and transmembrane serine protease 2 (TMPRSS2), combination with the synthetic androgen R1881 in parental LNCaP cells. Enzalutamide could inhibit the transcriptional activity of a mutant AR protein (W741C, mutation of Trp741 to Cys). Enzalutamide also prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. Kinase 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 Iscoves medium containing 10% fetal bovine serum (FBS). Two days prior to Enzalutamide treatment, the cells are grown in Iscoves medium containing 10% charcoal-stripped FBS (CS-FBS) to deprive of androgens. The cells are split and grown in Iscoves medium containing 10% CS-FBS with 100 pM of R1881 and increasing concentrations of Enzalutamide. After two days of incubation, reporter activities are assayed. Cell Assay: Enzalutamide is diluted in DMSO. LNCaP or LNCaP/AR cells (104 cells/well) are androgen-starved by growth in media containing 5-10% charcoal-stripped serum for 3-5 days. Then the cells are challenged with various concentrations of Enzalutamide in media containing 5-10% charcoal-stripped serum. |
|---|---|
| In Vivo | Enzalutamide induces great tumor regression in castrate male mice bearing LNCaP/AR xenografts at a dose of 10 mg/kg. |
| Animal model | Castration-resistant LNCaP/HR xenografts in male SCID mice |
| Formulation & Dosage | Formulated in 1% carboxymethyl cellulose, 0.1% Tween-80, 5% DMSO; 10 mg/kg; Oral gavage |
| References | Science. 2009 May 8;324(5928):787-90; Lancet. 2010 Apr 24;375(9724):1437-46. |
Related Posts
product name Enzalutamide (MDV3100)
Description: Enzalutamide (also known as MDV3100) is a second-generation androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. Enzalutamide is an orally bioavailable, organic, non-steroidal small molecule with potential antineoplastic activity. It has higher affinity to the AR compared to the first-generation AR inhibitors. It acts by blocking the binding of androgens to the AR, AR nuclear translocation, and the association of the AR with DNA. The AR is a 919-amino acid member of the steroid receptor transcription factor superfamily with different domains including an N-terminal regulation domain.
References: Science. 2009 May 8;324(5928):787-90; Lancet. 2010 Apr 24;375(9724):1437-46.
464.44
Formula
C21H16F4N4O2S
CAS No.
915087-33-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 92 mg/mL (198.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
15% DMSO+85% PEG 300: 10mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394534
| In Vitro |
In vitro activity: Enzalutamide has greater affinity to AR than Bicalutamide does in a competition assay with 16β-[18F]fluoro-5α-DHT (18-FDHT) in castration-resistant LNCaP/AR cells (AR-overexpressing). While Enzalutamide shows no agonism in LNCaP/AR prostate cells. Enzalutamide antagonizes induction of prostate-specific antigen (PSA) and transmembrane serine protease 2 (TMPRSS2), combination with the synthetic androgen R1881 in parental LNCaP cells. Enzalutamide could inhibit the transcriptional activity of a mutant AR protein (W741C, mutation of Trp741 to Cys). Enzalutamide also prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. Kinase 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 Iscoves medium containing 10% fetal bovine serum (FBS). Two days prior to Enzalutamide treatment, the cells are grown in Iscoves medium containing 10% charcoal-stripped FBS (CS-FBS) to deprive of androgens. The cells are split and grown in Iscoves medium containing 10% CS-FBS with 100 pM of R1881 and increasing concentrations of Enzalutamide. After two days of incubation, reporter activities are assayed. Cell Assay: Enzalutamide is diluted in DMSO. LNCaP or LNCaP/AR cells (104 cells/well) are androgen-starved by growth in media containing 5-10% charcoal-stripped serum for 3-5 days. Then the cells are challenged with various concentrations of Enzalutamide in media containing 5-10% charcoal-stripped serum. |
|---|---|
| In Vivo | Enzalutamide induces great tumor regression in castrate male mice bearing LNCaP/AR xenografts at a dose of 10 mg/kg. |
| Animal model | Castration-resistant LNCaP/HR xenografts in male SCID mice |
| Formulation & Dosage | Formulated in 1% carboxymethyl cellulose, 0.1% Tween-80, 5% DMSO; 10 mg/kg; Oral gavage |
| References | Science. 2009 May 8;324(5928):787-90; Lancet. 2010 Apr 24;375(9724):1437-46. |