several conserved residues critical for ligand binding. Finally, a glutamine-rich (Q-rich) domain is located in the C-terminal region of the protein and is involved in co-activator recruitment and transactivation. Ligands AhR ligands have been generally classified into two categories, synthetic or naturally occurring. The first ligands to be discovered were synthetic and members of the halogenated aromatic hydrocarbons (polychlorinated dibenzodioxins, dibenzofurans and biphenyls) and polycyclic aromatic hydrocarbons (3-methylcholanthrene, benzo[a]pyrene, benzanthracenes and benzoflavones). A range of synthetic ligands have been designed to target the possible future treatment of breast cancer. Research has focused on naturally occurring compounds with the hope of identifying an endogenous ligand. Naturally occurring compounds that have been identified as ligands of Ahr include derivatives of tryptophan such as indigo dye and indirubin, tetrapyrroles such as bilirubin, the arachidonic acid metabolites lipoxin A4 and prostaglandin G, modified low-density lipoprotein and several dietary carotenoids. One assumption made in the search for an endogenous ligand is that the ligand will be a receptor agonist. However, work by Savouret et al. has shown this may not be the case since their findings demonstrate that 7-ketocholesterol competitively inhibits Ahr signal transduction. Carbidopa is a selective aryl hydrocarbon receptor modulator (SAhRM). Other SAhRMs include microbial-derived 1,4-dihydroxy-2-napthoic acid and plant-derived 3,3-diindolylmethane. Indolocarbazole (ICZ) is one of the strongest non-halogenated agonists for AHR in vitro reported. Signaling pathway Cytosolic complex Non-ligand bound Ahr is retained in the cytoplasm as an inactive protein complex consisting of a dimer of Hsp90, prostaglandin E synthase 3 (PTGES3, p23) and a single molecule of the immunophilin-like AH receptor-interacting protein, also known as hepatitis B virus X-associated protein 2 (XAP2), AhR interacting protein (AIP), and AhR-activated 9 (ARA9). The dimer of Hsp90, along with PTGES3 (p23), has a multifunctional role in the protection of the receptor from proteolysis, constraining the receptor in a conformation receptive to ligand binding and preventing the premature binding of ARNT. AIP interacts with carboxyl-terminal of Hsp90 and binds to the AhR nuclear localization sequence (NLS) preventing the inappropriate trafficking of the receptor into the nucleus. Receptor activation Upon ligand binding to AhR, AIP is released resulting in exposure of the NLS, which is located in the bHLH region, leading to import into the nucleus. It is presumed that once in the nucleus, Hsp90 dissociates exposing the two PAS domains allowing the binding of ARNT. The activated AhR/ARNT heterodimer complex is then capable of either directly