Galeterone

SKU: orb1300706

Description

Galeterone (VN 124) is an orally active small molecule that antagonizes the androgen receptor, inhibits CYP17A1 lyase activity, and reduces androgen receptor protein levels, thereby suppressing androgen signaling in prostate cancer. It is used in research for studying castration-resistant prostate cancer mechanisms and has been evaluated in both in vitro assays and in vivo xenograft models.

Research Area

Metabolism Research

Key Properties

• CAS Number: 851983-85-2
• MW: 388.55
• Purity: 99.77% (May vary between batches)
• Formula: C₂₆H₃₂N₂O
• SMILES: C[C@]12CC[C@H]3[C@@H](CC=C4C[C@@H](O)CC[C@]34C)[C@@H]1CC=C2n1cnc2ccccc12
• Target: Androgen Receptor,Cytochromes P450
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.15 mM);DMSO:19.4 mg/mL (49.93 mM);Ethanol:19.4 mg/mL (49.93 mM)

Bioactivity

• Target IC50:
  Androgen receptor:384 nM|CYP17:300 nM
• In Vivo:
  Administration of Galeterone at 50 mg/kg twice daily is very effective at inhibiting the growth of androgen-dependent LAPC4 human prostate tumor xenograft, with a 93.8% reduction in the mean final tumor volume compared with controls, and it is also significantly more effective than castration. Treatment of Galeterone (0.13 mM/kg twice daily) or Galeterone (0.13 mmol/kg twice daily) plus castration induces regression of LAPC4 tumor xenografts in SCID mice by 26.55% and 60.67%, respectively. Treatments with Galeterone or Galeterone plus castration causes marked reduction in AR protein of 10- and 5-fold, respectively.
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• In Vitro:
  Galeterone is effective at preventing binding of [3H]-R1881 to the mutant LNCaP AR (T877A) with IC50 of 845 nM. Galeterone inhibits the DHT-induced proliferation of LNCaP and LAPC4 cells in a dose-dependent manner with IC50 of 6 μM and 3.2 μM, respectively. Galeterone also inhibits the binding of [3H]-R1881 to the T575A mutant AR in PC3 cells with IC50 of 454 nM. Galeterone potently inhibits the proliferation of LNCaP and LAPC4 cells in the absence of DHT stimulation with IC50 of 2.6 μM and 4 μM, respectively. Furthermore, Galeterone treatment increases the degradation rate of the AR in a dose-dependent manner. Galeterone potently inhibits the growth of the androgen-independent cell lines PC-3 and DU-145 in a dose-dependent manner with GI50 of 7.82 μM and 7.55 μM, respectively. Galeterone induces the endoplasmic reticulum stress response resulting in down-regulation of cyclin D1 protein expression and cyclin E2 mRNA. Galeterone effectively inhibits proliferation of HP-LNCaP and C4-2B cell lines with IC50 of 2.9 μM and 9.7 μM, respectively. Galeterone treatment at 1 μM effectively inhibits androgen receptor activation in LNCaP cells (50%) and HP-LNCaP cells (70%). Galeterone decreases activation of the androgen receptor in both LNCaP cells and HP-LNCaP cells with IC50 of 1 μM and 411 nM, respectively, and down-regulates androgen receptor protein expression by 50% after 24 hour of treatment. Galeterone reduces AR protein and mRNA expression, antagonizes AR-dependent promoter activation induced by androgen, and significantly reduces the phospho-4EBP1 levels.
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• Cell Research:
  Cells are seeded in 24 well multi-well plates. Cells are treated with the increasing concentration of Galeterone in steroid free medium with or without 1 nM DHT (LNCaP), or 10 nM DHT (LAPC4) and allowed to grow for 7 days. The number of viable cells is compared by MTT assay (LAPC4) or XTT assay (LNCaP) on the 7th day. (Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, Galeterone, inhibit, AndrogenReceptor, Androgen Receptor, CYPs, CYP17, Cytochrome P450, TOK 001, TOK001, TOK-001, VN 124, VN/124-1, VN124, VN-124, VN-124-1

Compound Identifiers

PubChem CID

11188409