Orteronel

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Orteronel
Orteronel.svg
Identifiers
CAS number 566939-85-3 YesY
PubChem 9883029
ChemSpider 8058704
UNII UE5K2FNS92
KEGG D10146 YesY
ChEMBL CHEMBL1921976
Jmol-3D images Image 1
Properties
Molecular formula C18H17N3O2
Molar mass 307.35 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Orteronel (TAK-700) is an antiandrogen that was being developed for the treatment of cancer by Takeda Pharmaceutical Company in conjunction with Millennium Pharmaceuticals.[1] It completed two phase III clinical trials for metastatic, hormone-refractory prostate cancer but failed to extend overall survival rates, and development was voluntarily terminated as a result.[2]

Orteronel is an androgen biosynthesis inhibitor. It selectively inhibits the enzyme CYP17A1[3] which is expressed in testicular, adrenal, and prostatic tumor tissues. CYP17 catalyzes two sequential reactions: (a) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by its 17α-hydroxylase activity, and (b) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by its 17,20-lyase activity.[4] DHEA and androstenedione are androgens and precursors of testosterone. Inhibition of CYP17 activity thus decreases circulating levels of testosterone.

See also[edit]

References[edit]

  1. ^ Millennium and Takeda Announce Advancement of Prostate Cancer Program, Millennium Pharmaceuticals
  2. ^ MarketWatch (2014). "Takeda Announces Termination of Orteronel (TAK-700) Development for Prostate Cancer in Japan, U.S.A. and Europe". 
  3. ^ Yamaoka, M; Hara, T; Hitaka, T; Kaku, T; Takeuchi, T; Takahashi, J; Asahi, S; Miki, H et al. (2012). "Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: Effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys". The Journal of steroid biochemistry and molecular biology 129 (3–5): 115–28. doi:10.1016/j.jsbmb.2012.01.001. PMID 22249003. 
  4. ^ Attard G, Belldegrun AS, de Bono JS (December 2005). "Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer". BJU Int. 96 (9): 1241–6. doi:10.1111/j.1464-410X.2005.05821.x. PMID 16287438.