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
CAS Number	566939-85-3  Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:231353
ChEMBL	ChEMBL1921976
ChemSpider	8058704
KEGG	D10146  Y
PubChem CID	9883029
UNII	UE5K2FNS92
InChI InChI=1S/C18H17N3O2/c1-19-17(22)14-3-2-13-9-15(5-4-12(13)8-14)18(23)6-7-21-11-20-10-16(18)21/h2-5,8-11,23H,6-7H2,1H3,(H,19,22)
SMILES O=C(NC)c2ccc1cc(ccc1c2)C4(O)c3cncn3CC4
Properties
Chemical formula	C18H17N3O2
Molar mass	307.353 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Orteronel (TAK-700) is a nonsteroidal CYP17A1 inhibitor 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.

References

1. Millennium and Takeda Announce Advancement of Prostate Cancer Program ^{[ permanent dead link ‍]}, 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. S2CID   20204862.
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. S2CID   36575315.