MDV3100

M.Wt: 464.44
Formula: C₂₁H₁₆F₄N₄O₂S
Solubility: DMSO
Purity: >99%
Storage: at -20℃ 2 years
CAS No.: 915087-33-1

Price and Availability of MDV3100:

Biological Activity of MDV3100:

MDV3100 is an androgen-receptor (AR) antagonist with IC50 of 36 nM. MDV3100 has greater affinity to AR than bicalutamide does in a competition assay with 16β-[18F]fluoro-5α-DHT (18-FDHT). MDV3100 shows no agonism in LNCaP/AR (AR-overexpressing) prostate cells. MDV3100 antagonizes induction of prostate-specific antigen (PSA) and transmembrane serine protease 2 (TMPRSS2), combination with the synthetic androgen R1881 in parental LNCaP cells. MDV3100 could inhibit the transcriptional activity of a mutant AR protein (W741C, mutation of Trp741 to Cys). MDV3100 induces great tumor regression in castrate male mice bearing LNCaP/AR xenografts at a dose of 10 mg/kg. ^[1] MDV3100 also prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. ^[2] MDV3100 is currently in Phase III clinical trials in progressive metastatic prostate cancer. MDV3100 is originally developed by Medivation.

Protocol:

Biological Assay:
MDV3100 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 MDV3100 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 MDV3100 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 MDV3100. After two days of incubation, reporter activities are assayed. ^[3]

Cell Assay:
MDV3100 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 MDV3100 (1 to 10000 nM) in media containing 5-10% charcoal-stripped serum.

Animal Studies:
MDV3100 is formulated in 1% carboxymethyl cellulose, 0.1% Tween-80, 5% DMSO and administered by gavage daily at a dose of 10 mg/kg.

References on MDV3100:

[1] Tran C, et al, Science, 2009, 324 (5928), 787-790.

[2] Scher HI, et al, Lancet, 2010, 375(9724), 1437-1446.

[3] http://worldwide.espacenet.com/publicationDetails/originalDocument?CC=US&NR=2007254933A1&KC=A1&FT=D&ND=4&date=20071101&DB=EPODOC&locale=en_EP

MSDS
Batch S125001: H-NMR   COA

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