Development of selective aryl hydrocarbon receptor modulators for treatment of breast cancer
- 1 September 1999
- journal article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 8 (9) , 1385-1396
- https://doi.org/10.1517/13543784.8.9.1385
Abstract
The aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix DNA-binding protein that forms a transcriptionally-active heterodimer with the AhR nuclear translocator (Arnt) protein. The nuclear AhR complex is a ligand-induced transcription factor and the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a high affinity ligand for the AhR. TCDD induces a diverse spectrum of tissue-, sex- and species-specific biochemical and toxic responses in Ah-responsive cells/tissues including the inhibition of 17β-oestradiol (E2)-induced gene expression in the rodent uterus and mammary and in human breast cancer cell lines. TCDD also inhibits spontaneous and carcinogen-induced mammary tumour formation and growth in rodent models. Research in this laboratory has utilised the AhR as a target for developing anticancer drugs for treatment of breast cancer and two different structural classes of selective AhR modulators (SAhRMs) have been developed. Alternate-substituted (1,3,6,8- and 2,4,6,8-) alkyl po...Keywords
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