Palovarotene (R-667, RO-3300074) was developed by Roche Holding AG as a selective retinoic acid receptor gamma agonist for the treatment of emphysema. Phase I clinical trials of palovarotene in patients with emphysema demonstrated that the drug is well tolerated, with improvements observed in markers of emphysema progression. Unlike all-trans retinoic acid, the pharmacokinetic profile of palovarotene appears to be dose-proportional. However, those studies were discontinued. Palovarotene is also being investigated in phase II of the clinical trial in the treatment of Fibrodysplasia Ossificans Progressiva (FOP). Palovarotene received Fast Track designation from the U.S. Food and Drug Administration (FDA) and orphan designations for the treatment of FOP from both the FDA and the European Medicines Agency (EMA).

Tazarotene is a prodrug and a member of the acetylenic class of retinoids. Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. When treating acne tazarotene may be taken in conjunction with an oral antibiotic. Tazarotene has been shown in peer-reviewed double blinded studies to reduce: mottling and hyperpigmentation, sallowness, fine wrinkling and coarse wrinkling in sun damaged skin. Histological studies have shown that long term (greater than 1 year) use of Tazarotene is associated with a significant reduction in atypical melanocytes and keratocytes - cells considered to be precursors of skin cancer. Some studies have shown long term use of Tazarotene to be associated with increased collagen production and better organization of skin collagen bundles. Although the exact mechanism of tazarotene action is not known, studies have shown that the active form of the drug (tazarotenic acid) binds to all three members of the retinoic acid receptor (RAR) family: RARa, RARb, and RARg, but shows relative selectivity for RARb, and RARg and may modify gene expression. It also has affinity for RXR receptors. Tazarotene is used to treat psoriasis, acne and sun damaged skin (photodamage). Tazarotene is marketed as Tazorac, Avage, Zorac, and Fabior.

Adapalene is a topical retinoid primarily used in the treatment of acne and is used (off-label) to treat keratosis pilaris as well as other skin conditions. Galderma currently markets it under the trade names Differin in some countries, and Adaferin in India. Adapalene acts on retinoid receptors. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization, and inflammatory processes all of which represent important features in the pathology of acne vulgaris. Mechanistically, adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cytosolic receptor protein. Although the exact mode of action of adapalene is unknown, it is suggested that topical adapalene normalizes the differentiation of follicular epithelial cells resulting in decreased microcomedone formation.

Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro. Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells. In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma.

The synthetic retinoid AGN-193109 is a potent pan retinoic acid receptor (RAR) antagonist. It has been shown to block the antiproliferative effect of retinoids in cultured human cervical cancer cells. AGN-193109 is a potent RAR antagonist and a potential antidote of retinoid intoxication in vivo. In addition to potential clinical applications in the prevention and treatment of retinoid toxicity, AGN-193109 should provide a powerful experimental tool for the elucidation of retinoid biology.

BMS-453 (BMS-189453) is a potent and selective RAR agonist and a potent testicular toxin. In Sprague Dawley rats at daily oral doses of 15, 60, or 240 mg/kg for 1 month, BMS-189453 produced increases in leukocyte counts, alkaline phosphatase and alanine aminotransferase levels, and marked testicular degeneration and atrophy at all doses. BMS-189453 reduced MMP-1 expression in HIG-82 synovial fibroblasts in culture. BMS-189453 treatment blocked the clinical progression of arthritis beyond soft tissue inflammation in the CIA model. In the SCWA model, BMS-189453 treatment resulted in significantly reduced swelling with no notable progression to joint distortion/destruction. Improvement in clinical and histologic variables in 2 separate animal models, along with simultaneous reduction in MMP expression in the affected joint, suggests that RAR antagonists such as BMS-189453 may be useful as agents to treat rheumatoid arthritis and for determining the role of MMP in disease progression.

Arotinoid acid (Ro 13-7410, TTNPB) is the third generation of synthetic retinoid, which was developed for the treatment of psoriasis and other hyperkeratotic skin disorders. The therapeutically active dose is less than 0.5 ug/kg body weight/day. Arotinoid Acid is an agonist of RAR with IC50 values of 3.8nM, 4nM and 4.5nM for RARα, RARβ and RARγ, respectively. Naturally occurring vitamin A-like compounds such as all-trans-retinoic acid (atRA) are responsible for regulating growth and differentiation in the cell, and many of them have shown promising anticancer effects. Bioassays in vivo and in culture showed that TTNPB is more potent than atRA, mainly because of its higher molecular stability. The effects of TTNPB, which include control of epidermal keratinocytes and murine teratocarcinoma cells and antiproliferative effects on Kaposi´s sarcoma, breast cancer, cervical carcinoma, and leukemia cells have been known for some time. Furthermore, TTNPB proved to be 100 times more effective than atRA in inhibiting the growth of breast cancer cells. However, TTNPB is more teratogenic than atRA, which limits its use as a chemotherapeutic agent in humans. Arotinoid acid (AGN193198) has being shown to be useful for the treatment of pancreatic cancer among other types of cancer.

EC23, also known as AGN 190205, is photostable synthetic analog of All-trans retinoic acid (ATRA). EC23 is an agonist of retinoic acid receptors: alpha, beta and gamma, while having no appreciable activity for retinoid X receptors and weakly activates aryl hydrocarbon receptor. It was shown, that EC23 induced neural differentiation in human pluripotent embryonic stem cells.