Editing Retinoid (section)

== Structure ==
The basic structure of the hydrophobic retinoid molecule consists of a cyclic end group, a [[polyene]] side chain and a polar end group. The [[conjugated system]] formed by alternating C=C double bonds in the polyene side chain are responsible for the color of retinoids (typically yellow, orange, or red). Hence, many retinoids are [[chromophore]]s. Alternation of side chains and end groups creates the various classes of retinoids.{{cn|date=January 2025}}

First generation retinoids are produced naturally in the body and interact with their normal biological counterparts, such as [[retinol binding protein 4]] for retinol, [[Retinoic acid receptor|retinoid receptors]] for [[all-trans-retinoic acid]] or [[9-cis-retinoic acid]].<ref>{{cite journal | vauthors = Duester G | title = Retinoic acid synthesis and signaling during early organogenesis | journal = Cell | volume = 134 | issue = 6 | pages = 921–931 | date = September 2008 | pmid = 18805086 | pmc = 2632951 | doi = 10.1016/j.cell.2008.09.002 }}</ref> [[13-cis retinoic acid]] has an unknown biological pathway but appears to act as a growth factor.<ref>{{cite journal | vauthors = Brzezinski P, Borowska K, Chiriac A, Smigielski J | title = Adverse effects of isotretinoin: A large, retrospective review | journal = Dermatologic Therapy | volume = 30 | issue = 4 | pages = e12483 | date = July 2017 | pmid = 28295859 | doi = 10.1111/dth.12483 | doi-access = free }}</ref>

Second generation retinoids have a mixed effect and interact mainly with signaling in the skin.<ref>{{Cite web |date=2013-12-02 |title=Soriatane (Acitretin): Side Effects, Uses, Dosage, Interactions, Warnings |website=RxList |url=http://www.rxlist.com/soriatane-drug.htm |url-status=live |access-date=2024-08-30 |archive-url=https://web.archive.org/web/20131202230458/http://www.rxlist.com/soriatane-drug.htm |archive-date=2013-12-02 }}</ref>{{verification failed|reason=Source doesn't use the words "interact" (except in relation to other drugs) or "signaling" and is about soriatane specifically, not second generation retinoids generally|date=August 2024}}

Third generation retinoids have narrow biological roles due to their constrained structure, with adapalene mimicking the effects of [[isotretinoin]],<ref name = "Mukherjee_2006">{{cite journal | vauthors = Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G | title = Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety | journal = Clinical Interventions in Aging | volume = 1 | issue = 4 | pages = 327–348 | date = 2006 | pmid = 18046911 | pmc = 2699641 | doi = 10.2147/ciia.2006.1.4.327 | doi-access = free }}</ref> [[bexarotene]] binding only the [[Retinoid X receptor]]s, and [[tazarotene]] binding the [[Retinoic acid receptor beta]] and [[Retinoic acid receptor gamma]] forms.<ref>{{Cite journal | vauthors =  Duvic M, Nagpal S, Asano AT, Chandraratna RA |date=August 1997 |title=Molecular mechanisms of tazarotene action in psoriasis |url=https://linkinghub.elsevier.com/retrieve/pii/S0190962297803969 |journal=Journal of the American Academy of Dermatology |volume=37 |issue=2 |pages=S18–S24 |doi=10.1016/s0190-9622(97)80396-9 |issn=0190-9622|url-access=subscription }}</ref>

The only fourth generation retinoid, Trifarotene, binds selectively to the RAR-y receptor. It was approved for use in the US in 2019.<ref>{{cite web |title=Drug Approval Package: Aklief | website=US Food and Drug Administration |date=October 21, 2019 |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211527Orig1s000TOC.cfm | archive-url=https://web.archive.org/web/20191119042411/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211527Orig1s000TOC.cfm |archive-date=19 November 2019 |url-status=dead |access-date=31 December 2021}}</ref>