Home Endocrinology & Hormones Androgen Receptor antagonist - P450 (e.g. CYP17) inhibitor Galeterone For research use only.

Galeterone

Synonyms: TOK-001

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.

Galeterone Chemical Structure

Galeterone Chemical Structure

CAS No. 851983-85-2

Purity & Quality Control

Galeterone Related Products

Signaling Pathway

Androgen Receptor Signaling Pathways

Androgen Receptor Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human PC3 cells Function assay Displacement of [3H]R1881 from androgen receptor in human PC3 cells, EC50=0.405 μM 25591066
human LNCaP cells Function assay 2 h Displacement of [3H]R1881 from AR in human LNCaP cells after 2 hrs by scintillation counting analysis, EC50=0.67 μM 23713567
human CWR22Rv1 cells Function assay Induction of apoptosis in human CWR22Rv1 cells assessed as induction of PARP cleavage 23713567
human LNCAP cells Function assay 5 μM 48 h Down regulation of AR protein expression in human LNCAP cells at 5 uM after 48 hrs by DAPI staining-based immunocytochemical analysis 23713567
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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
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]
Kinase Assay 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 Research 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.
In Vivo
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]
Animal Research 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
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02729376 Completed
Healthy
LTN PHARMACEUTICALS INC.
 March 2016 Phase 1

Chemical Information & Solubility

Molecular Weight 388.55 Formula

C26H32N2O
CAS No. 851983-85-2 SDF Download Galeterone SDF
Smiles CC12CCC(CC1=CCC3C2CCC4(C3CC=C4N5C=NC6=CC=CC=C65)C)O
Storage (From the date of receipt)

In vitro
Batch:

Ethanol : 40 mg/mL

DMSO : 24 mg/mL ( (61.76 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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