Talarozole Explained
| Verifiedfields: | changed |
| Verifiedrevid: | 451730052 |
| Iupac Name: | N-(2-Benzothioazolyl)-N-[4-[2-ethyl-1-(1,2,4-triazo-1-yl)butyl]phenyl]amine |
| Routes Of Administration: | By mouth, topical |
| Cas Number: | 201410-53-9 |
| Atc Prefix: | none |
| Pubchem: | 9799888 |
| Chebi: | 101854 |
| Unii: | XKD9N5CJ6W |
| Chemspiderid: | 7975653 |
| C: | 21 |
| H: | 23 |
| N: | 5 |
| S: | 1 |
| Smiles: | c2ncnn2C(C(CC)CC)c(cc3)ccc3Nc4nc1ccccc1s4 |
| Stdinchi: | 1S/C21H23N5S/c1-3-15(4-2)20(26-14-22-13-23-26)16-9-11-17(12-10-16)24-21-25-18-7-5-6-8-19(18)27-21/h5-15,20H,3-4H2,1-2H3,(H,24,25) |
| Stdinchikey: | SNFYYXUGUBUECJ-UHFFFAOYSA-N |
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).[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).[5]
Notes and References
- Web site: Talarozole . AdisInsight . Springer Nature Switzerland AG .
- Zhu L, Kamalathevan P, Koneva LA, Zarebska JM, Chanalaris A, Ismail H, Wiberg A, Ng M, Muhammad H, Walsby-Tickle J, McCullagh JS, Watt FE, Sansom SN, Furniss D, Gardiner MD, Vincent TL, Riley N, Spiteri M, McNab I, Little C, Cogswell L, Critchley P, Giele H, Shirley R . 6 . 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 . 36542696 . 10.1126/scitranslmed.abm4054 . 10044/1/101589 . free .
- Nelson CH, Buttrick BR, Isoherranen N . 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 . 23688132 . 4366427 . 10.2174/1568026611313120004 .
- Giltaire S, Herphelin F, Frankart A, Hérin M, Stoppie P, Poumay Y . 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 . 19120344 . 10.1111/j.1365-2133.2008.08960.x . 205258196 .
- Gomaa MS, Lim AS, Lau SC, Watts AM, Illingworth NA, Bridgens CE, Veal GJ, Redfern CP, Brancale A, Armstrong JL, Simons C . 6 . 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 . 22989911 . 10.1016/j.bmc.2012.08.044 .
