Galeterone

Catalog No.S2803 Batch:S280301

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Technical Data

Formula

C26H32N2O
Molecular Weight 388.55 CAS No. 851983-85-2
Solubility (25°C)* In vitro Ethanol 40 mg/mL (102.94 mM)
DMSO 24 mg/mL (61.76 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Galeterone (TOK-001) is a selective CYP17 inhibitor and androgen receptor (AR) antagonist with IC50 of 300 nM and 384 nM, respectively, and is a potent inhibitor of human prostate tumor growth. Phase 2.
Targets
CYP17 [1]
(Cell-free assay)		 Androgen Receptor [1]
(PC3AR)
300 nM 384 nM
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. [1] 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. [2] 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. [3] 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. [4] Galeterone reduces AR protein and mRNA expression, antagonizes AR-dependent promoter activation induced by androgen, and significantly reduces the phospho-4EBP1 levels. [6]
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. [1] 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. [2]

Protocol (from reference)

Kinase Assay:

[1]
  • In vitro assay of CYP17

    The in vitro CYP17 inhibitory activity of Galeterone is evaluated using rapid acetic acid releasing assay (AARA), utilizing intact P450c17-expressing E. coli as the enzyme source. It involves the use of [21-3H]-17α-hydroxypregnenolone as the substrate, and CYP17 activity is measured by the amount of tritiated acetic acid formed during the cleavage of the C-21 side chain of the substrate. IC50 value is obtained directly from plots relating percentage inhibition versus inhibitor concentration over appropriate ranges.
Cell Assay:

[2]
  • Cell lines

    LNCaP and LAPC4

  • Concentrations

    Dissolved in DMSO, final concentrations ~20 μM

  • Incubation Time

    7 days

  • Method

    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.
Animal Study:

[1]
  • Animal Models

    Male severe combined immunodeficient (SCID) mice inoculated subcutaneously (s.c.) with LAPC4 cells

  • Dosages

    50 mg/kg

  • Administration

    Injection s.c. twice daily

Customer Product Validation

, , Biochem Biophys Res Commun, 2016, 477(4):1005-10.

Selleck's Galeterone has been cited by 6 publications

Desorption Electrospray Ionization Mass Spectrometry Assay for Label-Free Characterization of SULT2B1b Enzyme Kinetics [ ChemMedChem, 2022, e202200043] PubMed: 35080134
Galeterone sensitizes breast cancer to chemotherapy via targeting MNK/eIF4E and β-catenin [ Cancer Chemother Pharmacol, 2020, 10.1007/s00280-020-04195-w] PubMed: 33159561
New steroidal oxazolines, benzoxazoles and benzimidazoles related to abiraterone and galeterone. [ Steroids, 2020, 153:108534] PubMed: 31678134
Comparison of [17(20)E]-21-Norpregnene oxazolinyl and benzoxazolyl derivatives as inhibitors of CYP17A1 activity and prostate carcinoma cells growth [ Steroids, 2018, 129:24-34] PubMed: 29183745
Conjugates of 17-substituted testosterone and epitestosterone with pyropheophorbide a differing in the length of linkers [Zolottsev VA, et al. Steroids, 2018, 138:82-90] PubMed: 30033342
Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis [Udhane SS, et al. Biochem Biophys Res Commun, 2016, 477(4):1005-10] PubMed: 27395338

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.