Talarozole

Talarozole
Clinical data
Routes of
administration		By mouth, topical
ATC code
  • none
Identifiers
  • N-(2-Benzothioazolyl)-N-[4-[2-ethyl-1-(1,2,4-triazo-1-yl)butyl]phenyl]amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H23N5S
Molar mass377.51 g·mol−1
3D model (JSmol)
  • c2ncnn2C(C(CC)CC)c(cc3)ccc3Nc4nc1ccccc1s4
  • InChI=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) X markN
  • Key:SNFYYXUGUBUECJ-UHFFFAOYSA-N X markN
 X markNcheckY (what is this?)  (verify)

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. However, its effect in increasing retinoic acid is now being investigated in hand and knee osteoarthritis.

Talarozole inhibits the metabolism of retinoic acid by blocking cytochrome P450 enzyme CYP26 isoenzymes (CYP26A1 and possibly also CYP26B1), retinoic acid hydroxylases. Because of this mechanism, it is called a retinoic acid metabolism blocking agent (RAMBA).

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).

References

  1. ↑ "Talarozole". AdisInsight. Springer Nature Switzerland AG.
  2. ↑ 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.
  3. 1 2 3 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.
  4. ↑ 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.
  5. ↑ 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.