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]
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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 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 edit
- ^ "Talarozole". AdisInsight. Springer Nature Switzerland AG.
- ^ Zhu L, Kamalathevan P, Koneva LA, Zarebska JM, Chanalaris A, Ismail H, et al. (December 2022). "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. doi:10.1126/scitranslmed.abm4054. hdl:10044/1/101589. PMID 36542696.
- ^ a b c Nelson CH, Buttrick BR, Isoherranen N (2013). "Therapeutic potential of the inhibition of the retinoic acid hydroxylases CYP26A1 and CYP26B1 by xenobiotics". Current Topics in Medicinal Chemistry. 13 (12): 1402–1428. doi:10.2174/1568026611313120004. PMC 4366427. PMID 23688132.
- ^ Giltaire S, Herphelin F, Frankart A, Hérin M, Stoppie P, Poumay Y (March 2009). "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. doi:10.1111/j.1365-2133.2008.08960.x. PMID 19120344. S2CID 205258196.
- ^ Gomaa MS, Lim AS, Lau SC, Watts AM, Illingworth NA, Bridgens CE, et al. (October 2012). "Synthesis and CYP26A1 inhibitory activity of novel methyl 3-[4-(arylamino)phenyl]-3-(azole)-2,2-dimethylpropanoates". Bioorganic & Medicinal Chemistry. 20 (20): 6080–6088. doi:10.1016/j.bmc.2012.08.044. PMID 22989911.
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