851983-85-2

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 (Item No. 11597) or gefitinib (Item No. 13166) for growth inhibition.

Galeterone is an androgen receptor antagonist and CYP17A1 enzyme inhibitor.

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

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.

GENERAL STEPS: (3BETA)-17-(1H-benzimidazol-1-yl)androsta-5,16-dien-3-ol 3-acetate (1.3 g, 3.02 mmol) was dissolved in methanol (20 mL) under an inert argon (Ar) atmosphere. To the resulting solution was added 10% potassium methanol (KOH) solution (8 mL). The reaction mixture was stirred at room temperature for 1.5 h. The reaction mixture was subsequently concentrated under reduced pressure to a volume of about 10 mL at about 40 °C. The concentrated solution was poured into ice water (300 mL), and the precipitated white precipitate was filtered, washed with water and dried. The target product (3β-hydroxy-17-(1H-benzimidazol-1-yl)androsta-5,16-diene) was obtained by solvent recrystallization over a mixture of ethyl acetate (EtOAc)/methanol (MeOH) (1.10 g, 94% yield), melting point 189-190 °C. Infrared spectra (CHCl3) showed absorption peaks located at 2934, 2339, 1609, 1490, 1453, 1291, 1040, 837, 808, 705, 663, 608, 578, 550, 517 cm-1 .1H NMR (300 MHz, CDCl3) δ 1.02 (s, 3H, 18-CH3) 1.07 (s, 3H, 19-CH3), 3.55 (m, 1H, 3α-H), 5.41 (br s, 1H, 6-H), 5.99 (s, 1H, 16-H), 7.30 (m, 2H, aromatic-H), 7.54 (s, 1H, aromatic-H), 7.80 (s, 1H, aromatic-H), 7.96 (s, 1H, 2X-H). . The calculated value of high resolution mass spectrometry (HRMS) was 411.2407 (C26H32ON2-Na+) and the measured value was 411.2396.

CYP17

Store at -20°C

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.

[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.