Chemistry:Talarozole
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| Routes of administration | By mouth, topical |
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| Formula | C21H23N5S |
| Molar mass | 377.51 g·mol−1 |
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Talarozole (formerly R115866, planned trade name Rambazole) was an investigational drug for the treatment of acne, psoriasis and other keratinization disorders. Development for that purpose has been discontinued.[1] However, its effect in increasing retinoic acid is now being investigated in hand osteoarthritis.[2]
Talarozole inhibits the metabolism of retinoic acid by blocking cytochrome P450 enzyme CYP26 isoenzymes (CYP26A1 and possibly also CYP26B1), retinoic acid hydroxylases.[3] Because of this mechanism, it is called a retinoic acid metabolism blocking agent (RAMBA).[3][4]
It has 750-fold higher potency than the earlier drug liarozole as well as greater selectivity, with more than 300-fold selectivity for inhibition of CYP26A1 over other steroid-metabolizing enzymes like CYP17A1 (17α-hydroxylase/17,20-lyase) and aromatase (CYP19A1).[3][5]
References
- ↑ "Talarozole". AdisInsight. Springer Nature Switzerland AG. http://adisinsight.springer.com/drugs/800020802.
- ↑ "Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis". Science Translational Medicine 14 (676): eabm4054. December 2022. doi:10.1126/scitranslmed.abm4054. PMID 36542696.
- ↑ 3.0 3.1 3.2 "Therapeutic potential of the inhibition of the retinoic acid hydroxylases CYP26A1 and CYP26B1 by xenobiotics". Current Topics in Medicinal Chemistry 13 (12): 1402–1428. 2013. doi:10.2174/1568026611313120004. PMID 23688132.
- ↑ "The CYP26 inhibitor R115866 potentiates the effects of all-trans retinoic acid on cultured human epidermal keratinocytes". The British Journal of Dermatology 160 (3): 505–513. March 2009. doi:10.1111/j.1365-2133.2008.08960.x. PMID 19120344.
- ↑ "Synthesis and CYP26A1 inhibitory activity of novel methyl 3-[4-(arylamino)phenyl]-3-(azole)-2,2-dimethylpropanoates". Bioorganic & Medicinal Chemistry 20 (20): 6080–6088. October 2012. doi:10.1016/j.bmc.2012.08.044. PMID 22989911.
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