Talarozole

Talarozole

Clinical data
Routes of administration	By mouth, topical
ATC code	none
Identifiers
IUPAC name N-(2-Benzothioazolyl)-N-[4-[2-ethyl-1-(1,2,4-triazo-1-yl)butyl]phenyl]amine
CAS Number	201410-53-9  Y
PubChem CID	9799888
ChemSpider	7975653  N
UNII	XKD9N5CJ6W
ChEBI	CHEBI:101854  N
CompTox Dashboard (EPA)	DTXSID70942185
Chemical and physical data
Formula	C21H23N5S
Molar mass	377.51 g·mol−1
3D model (JSmol)	Interactive image
SMILES c2ncnn2C(C(CC)CC)c(cc3)ccc3Nc4nc1ccccc1s4
InChI 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) N Key:SNFYYXUGUBUECJ-UHFFFAOYSA-N N
NY  (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. ^[1] However, its effect in increasing retinoic acid is now being investigated in hand and knee 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

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. 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.