Mechanism of action
For its use in cancer, its mechanism of action is unknown, but on a cellular level, laboratory tests show that tretinoin forces APL cells to differentiate and stops them from proliferating; in people there is evidence that it forces the primary cancerous promyelocytes to differentiate into their final form, allowing normal cells to take over the bone marrow. Recent study shows that ATRA inhibits and degrades active PIN1.For its use in acne, tretinoin (along with other retinoids) are vitamin A derivatives that act by binding to two nuclear receptor families within keratinocytes: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). These events contribute to the normalization of follicular keratinization and decreased cohesiveness of keratinocytes, resulting in reduced follicular occlusion and microcomedone formation. The retinoid-receptor complex competes for coactivator proteins of AP-1, a key transcription factor involved in inflammation. Retinoids also down-regulate expression of toll-like receptor (TLR)-2, which has been implicated in the inflammatory response in acne. Moreover, tretinoin and retinoids may enhance the penetration of other topical acne medications.The combination of the 10% benzoyl peroxide and light results in more than 50% degradation of tretinoin in about 2 hours and 95% in 24 hours. This lack of stability in the presence of light and oxidizing agents has led to the development of novel formulations of the drug. When microencapsulated tretinoin is exposed to benzoyl peroxide and light only 1% degradation takes place in about 4 hours and only 13% after 24 hours. Biosynthesis
Tretinoin is synthesized from beta-carotene.
The beta-carotene is firstly cleaved into beta-carotene 15-15-monooxygenase through site 1 double bond oxidized to epoxide. The epoxide is attacked by water to form diol in site 1. NADH, as a reduction agent, reduce the alcohol group to aldehydes. History
Tretinoin was co-developed for its use in acne by James Fulton and Albert Kligman when they were at University of Pennsylvania in the 1960s. Phase I trials, the first conducted on human subjects, were performed on inmates at Holmesburg Prison during a long-running regime of non-therapeutic and unethical testing on prison inmates at Holmesburg. The University of Pennsylvania held the patent for Retin-A, which it licensed to pharmaceutical companies.Treatment of acute promyelocytic leukemia was first introduced at Ruijin Hospital in Shanghai by Wang Zhenyi in a 1988 clinical trial. Etymology
The origin of the name tretinoin is uncertain, although several sources agree (one with probability, one with asserted certainty) that it probably comes from trans- + retinoic [acid] + -in, which is plausible given that tretinoin is the all-trans isomer of retinoic acid. The name isotretinoin is the same root tretinoin plus the prefix iso-. Regarding pronunciation, the following variants apply equally to both tretinoin and isotretinoin. Given that retinoic is pronounced , it is natural that  is a commonly heard pronunciation. Dictionary transcriptions also include  (tri-TIN-oh-in) and .