Orteronel

Orteronel
Names
IUPAC name
6-(7-Hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methylnaphthalene-2-carboxamide
Other names
TAK-700
Identifiers
566939-85-3 YesY
ChEMBL ChEMBL1921976
ChemSpider 8058704
Jmol 3D model Interactive image
KEGG D10146 YesY
PubChem 9883029
UNII UE5K2FNS92
Properties
C18H17N3O2
Molar mass 307.35 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 Â°C [77 Â°F], 100 kPa).
Infobox references

Orteronel (TAK-700) is a non-steroidal 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

References

  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.


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