Galeterone Chemical Properties

Melting point:

189-190℃

Boiling point:

564.5±60.0 °C(Predicted)

Density 

1.28

storage temp. 

-20°C Freezer

solubility 

Chloroform (Slightly), Ethyl Aceatae (Slightly, Heated)

pka

14.71±0.70(Predicted)

form 

Solid

color 

White to Off-White

InChIKey

PAFKTGFSEFKSQG-MRFMOSGMNA-N

SMILES

C1C[C@]2(C)C3CC[C@]4(C)C([n]5cnc6ccccc56)=CCC4C3CC=C2C[C@H]1O |&1:2,7,27,r|

Galeterone Usage And Synthesis

Description

Galeterone (TOK-001) is a small molecule oral drug that disrupts AR signaling by a novel triple mechanism: it potently and selectively inhibits CYP17 lyase, potently antagonizes AR and decreases AR protein levels (wild-type and mutant), leading to antitumor activity. Galeterone has shown significant anti-tumour activity with a well-tolerated safety profile in patients with CRPC in phase I and II clinical studies.

Uses

Galeterone is an androgen receptor antagonist and CYP17A1 enzyme inhibitor. It has been used in trials studying the treatment of Prostate Cancer.

Definition

ChEBI: Galeterone is a 3-hydroxy steroid. It has a role as an androgen.

Biological Activity

The cytochrome P450 (CYP) isoform CYP17 is also known as steroid 17α-hydroxylase/17,20 lyase because it catalyzes both 17α-hydroxylase and 17,20 lyase reactions in the synthesis of steroids, including androgens, estrogens, glucocorticoids, and mineralocorticoids. Galeterone is a CYP17 inhibitor (IC50 = 300 nM) that has been shown to competitively block synthetic androgen binding (EC50 = 845 nM) and to antagonize the androgen receptor in transcriptional activation assays. Galeterone can inhibit the growth of castration-resistant prostate cancer cells with an IC50 value of 2.9 μM and demonstrates synergy with everolimus or gefitinib for growth inhibition.

target

CYP17

storage

Store at -20°C

Mode of action

Galeterone is an orally bioavailable small-molecule androgen receptor modulator and CYP17 lyase inhibitor with potential antiandrogen activity. Galeterone exhibits three distinct mechanisms of action: 1) as an androgen receptor antagonist, 2) as a CYP17 lyase inhibitor and 3) by decreasing overall androgen receptor levels in prostate cancer tumors, all of which may result in a decrease in androgen-dependent growth signaling. Localized to the endoplasmic reticulum (ER), the cytochrome P450 enzyme CYP17 (P450C17 or CYP17A1) exhibits both 17alpha-hydroxylase and 17,20-lyase activities, and plays a key role in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.

References

[1]. devore n m, & scott e e. structures of cytochrome p450 17a1 with prostate cancer drugs abiraterone and tok-001. nature, 2012, 482: 116-119.
[2]. mallik i, davila m, tapia t, et al. androgen regulates cdc6 transcription through interactions between androgen receptor and e2f transcription factor in prostate cancer cells. biochimica et biophysica acta (bba) - molecular cell research, 2008,1783:1737-1744.
[3]. bruno r d, vasaitis t s, gediya l. k, et al. synthesis and biological evaluations of putative metabolically stable analogs of vn/124-1 (tok-001): head to head anti-tumor efficacy evaluation of vn/124-1 (tok-001) and abiraterone in lapc-4 human prostate cancer xenograft model. steroids, 2011,76: 1268-1279.

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