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 ;
PubChem CID	9799888;
ChemSpider	7975653 ;
UNII	XKD9N5CJ6W;
ChEBI	CHEBI:101854 ;
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) ; Key:SNFYYXUGUBUECJ-UHFFFAOYSA-N ;
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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.
^ 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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[AdisInsight-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.

[pmid23688132-3] 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.

[pmid19120344-4] 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.

[pmid22989911-5] 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.

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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)