D-15414

D-15414 is a nonsteroidal weak estrogen of the 2-phenylindole group which was never marketed.[1][2] It is the major metabolite of the selective estrogen receptor modulator (SERM) zindoxifene (D-16726).[3] D-15414 has high affinity for the estrogen receptor (ER) and inhibits the growth of ER-positive MCF-7 breast cancer cells in vitro.[3] However, contradictorily, subsequent research found that the drug produced fully estrogenic effects in vitro similarly to but less actively than estradiol, with no antiestrogenic activity observed.[1][2] The reason for the discrepancy between the findings is unclear, though may be due to methodology.[2] The unexpected estrogenic activity of D-15414 may be responsible for the failure of zindoxifene in clinical trials as a treatment for breast cancer.[1][4]

D-15414
Identifiers
IUPAC name
  • 1-ethyl-2-(4-hydroxyphenyl)-3-methylindol-5-ol
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H17NO2
Molar mass267.328 g·mol−1
3D model (JSmol)
SMILES
  • CCN1C2=C(C=C(C=C2)O)C(=C1C3=CC=C(C=C3)O)C
InChI
  • InChI=1S/C17H17NO2/c1-3-18-16-9-8-14(20)10-15(16)11(2)17(18)12-4-6-13(19)7-5-12/h4-10,19-20H,3H2,1-2H3
  • Key:BXTNOIWYTWIPEL-UHFFFAOYSA-N

References
  1. Jordan, V. Craig; Tormey, Douglass C. (1988). Endocrine Therapies in Breast and Prostate Cancer. Cancer Treatment and Research Ctar. Cancer Treatment and Research. Vol. 39. pp. 97–110. doi:10.1007/978-1-4613-1731-9_7. ISBN 978-1-4612-8974-6. ISSN 0927-3042.
  2. Robinson SP, Koch R, Jordan VC (1988). "In vitro estrogenic actions in rat and human cells of hydroxylated derivatives of D16726 (zindoxifene), an agent with known antimammary cancer activity in vivo". Cancer Res. 48 (4): 784–7. PMID 3338076.
  3. von Angerer E, Prekajac J, Berger M (1985). "The inhibitory effect of 5-acetoxy-2-(4-acetoxyphenyl)-1-ethyl-3-methylindole (D 16726) on estrogen-dependent mammary tumors". Eur J Cancer Clin Oncol. 21 (4): 531–7. doi:10.1016/0277-5379(85)90048-3. PMID 3924626.
  4. Philipp Y. Maximov; Russell E. McDaniel; V. Craig Jordan (23 July 2013). Tamoxifen: Pioneering Medicine in Breast Cancer. Springer Science & Business Media. pp. 170–. ISBN 978-3-0348-0664-0.



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