Tapinarof (also known as benvitimod, WB-1001; GSK-2894512), a therapeutic aryl hydrocarbon receptor agonist that selectively modulates the cytokine cascade deep under the skin, a process that rapidly decreases inflammations and skin plague. Tapinarof cream 1% (VTAMA®) is being developed by Dermavant Sciences Inc. (a subsidiary of Roivant Sciences Inc.) as a once-daily topical treatment for plaque psoriasis and atopic dermatitis. In May 2022, tapinarof cream 1% was approved in the USA for the topical treatment of plaque psoriasis in adults. Tapinarof cream 1% is also being investigated for the treatment of atopic dermatitis.

Ketoconazole is an azole antifungal. Ketoconazole was the first broad-spectrum oral antifungal agent available to treat systemic and superficial mycoses. Evidence of hepatotoxicity associated with its use emerged within the first few years of its approval. Due to its hepatotoxic side effects, oral ketoconazole was withdrawn from the European and Australian markets in 2013. The United States imposed strict relabeling requirements and restrictions for prescription, with Canada issuing a risk communication echoing these concerns. Today, oral ketoconazole is only indicated for endemic mycoses, where alternatives are not available or feasible. Meanwhile, topical ketoconazole is effective, safe, and widely prescribed for superficial mycoses, particularly as the first-line treatment for tinea versicolor. Topically administered ketoconazole is usually prescribed for fungal infections of the skin and mucous membranes, such as athlete's foot, ringworm, candidiasis (yeast infection or thrush), jock itch, and tinea versicolor. Topical ketoconazole is also used as a treatment for dandruff (seborrheic dermatitis of the scalp) and for seborrheic dermatitis on other areas of the body, perhaps acting in these conditions by suppressing levels of the fungus Malassezia furfur on the skin. Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone. Ketoconazole is active against clinical infections with Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis.

Mivotilate is an orally active hepatoprotective agent for the treatment of liver cirrhosis and hepatitis-B infection. Mivotilate was shown to exert multiple effects on the hepatic cytochrome P450 system, particularly to inhibit CYP2E1 expression and to up-regulate the CYP1A1 expression. The low oral bioavailability of Mivotilate in rats could be primarily attributed to poor absorption and considerable hepatic and gastrointestinal first-pass effects. The thermal reversible microemulsion system of YH439 greatly enhances the bioavailability of YH439 after oral administration. Mivotilate prevents mutagenesis caused by agents such as benzopyrene and reduces skin tumours induced by these agents.

Kynurenic acid is a product of the normal metabolism of amino acid L-tryptophan which has been shown to have a neuroactive profile. It exhibits activity against NMDA receptors and Neuronal acetylcholine receptor subunit alpha-7. It has been investigated as a potential therapeutic compound and as a biomarker in a number of neurological disorders. Although Kenyruic acid exhibits a poor penetration of the blood-brain barrier, it remains to be of particular interest to those researching Schizophrenia.

Indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, and its condensation product, 3,3'-diindolylmethane (DIM) exert several biological activities on cellular and molecular levels, which contribute to their well-recognized chemoprevention potential. ndole-3-carbinol is used for prevention of breast cancer, colon cancer, and other types of cancer. The National Institutes of Health (NIH) has reviewed indole-3-carbinol as a possible cancer preventive agent and is now sponsoring clinical research for breast cancer prevention. Indole-3-carbinol is also used for fibromyalgia, tumors inside the voice box (laryngeal papillomatosis) caused by a virus, tumors inside the respiratory tract (respiratory papillomatosis) caused by a virus, abnormal cell growth in the cervix (cervical dysplasia), and systemic lupus erythematosus (SLE). Indole-3-carbinol scavenges free radicals and induces various hepatic cytochrome P450 monooxygenases. Specifically, this agent induces the hepatic monooxygenase cytochrome P4501A1 (CYP1A1), resulting in increased 2-hydroxylation of estrogens and increased production of the chemoprotective estrogen 2-hydroxyestrone. Accumulating evidence indicates that the antitumor activity of indole-3- carbinol is attributable to its ability to interfere with multiple oncogenic signaling pathways governing cell cycle progression, survival, invasion, and other aggressive phenotypes of cancer cells. Reported signaling targets of indole-3- carbinol in various cancer cell lines include EGFR/Src, Akt/NF-B, stress responses, elastase, and Rho kinase. Moreover, indole-3-carbinol functions as a negative regulator of estrogen action in hormonesensitive cancer cells through the inhibition of estrogen receptor (ER)-alpha signaling and/or induction of cytochrome P-450-mediated estrogen metabolism, suggesting its clinical use in hormone-sensitive cancers.

The compound StemRegenin 1 (SR1) is a selective, cell-permeable, small molecule that promotes the self-renewal of human hematopoietic stem cells in culture. SR1 is an antagonist of the aryl hydrocarbon receptor. SR1 is the first small molecule that promotes robust expansion/self-renewal of human CD34 peripheral blood and cord blood hematopoietic stem cells (HSCs). The culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. SR1 can be potentially used for ex vivo expansion of normal HSCs or leukemic stem/progenitor cells

3-Methylcholanthrene a compound, which can activate both aryl hydrocarbon receptor (AhR) and estrogen receptor alpha. It is used to induce fibrosarcomas and skin carcinomas in laboratory animals. The daily exposure to 3-methylcholanthrene induced changes in both gene expression and epigenomic remodeling, which had led to premature ovarian failure.

Pifithrin-alpha is a small molecule p53 functional inhibitor reported to behave like an antiapoptotic agent in neurodegenerative models. Pifithrin-alpha is a prodrug that under physiological conditions spontaneously undergoes ring closure to yield pifithrin-beta. Pifithrin-beta demonstrated antiproliferative and neuroprotective effects in vitro. Pifithrin-beta is able to activate the aryl hydrocarbon receptor (AhR) in a complete independent way of the p53 inhibition.

Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodia Rutaecara, the dried unripe fruit of which is also known as Wu zhu yu (Wu Zhu Yu, interchangeably) or Evodia Fruit. Evodia Fruit used in Traditional Chinese Medicine for the purposes of warmth, intestinal comfort (specifically; to alleviate abdominal pain, acid regurgitation, nausea and diarrhea), dysmenorrheal, and fighting inflammation and infections. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and thermo-regulative effects. Evodiamine has evolved a superior ability to bind various proteins including TRPV1, the aryl hydrocarbon receptor (AhR), and topoisomerases I and II. There are currently no human studies on evodia rutaecarpa berries or evodiamine.

CH223191 is a ligand-selective antagonist of the aryl hydrocarbon (dioxin) receptor (AhR), a ligand-dependent transcription factor that produces a wide range of biological and toxic effects in many species and tissues.