Talarozole

{{Short description|Chemical compound}}

{{Infobox drug

| Verifiedfields = changed

| verifiedrevid = 451730052

| IUPAC_name = N-(2-Benzothioazolyl)-N-[4-[2-ethyl-1-(1,2,4-triazo-1-yl)butyl]phenyl]amine

| image =Talarozole_skeletal.svg

| tradename =

| pregnancy_AU =

| pregnancy_category =

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US =

| legal_status =

| routes_of_administration = By mouth, topical

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 201410-53-9

| ATC_prefix = none

| ATC_suffix =

| ATC_supplemental =

| PubChem = 9799888

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 101854

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = XKD9N5CJ6W

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 7975653

| chemical_formula =

| C=21 | H=23 | N=5 | S=1

| smiles = c2ncnn2C(C(CC)CC)c(cc3)ccc3Nc4nc1ccccc1s4

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| 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_Ref = {{stdinchicite|changed|chemspider}}

| 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.{{Cite web|url=http://adisinsight.springer.com/drugs/800020802|title = Talarozole | work = AdisInsight | publisher = Springer Nature Switzerland AG }} However, its effect in increasing retinoic acid is now being investigated in hand and knee osteoarthritis.{{cite journal | vauthors = 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 | display-authors = 6 | title = Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis | journal = Science Translational Medicine | volume = 14 | issue = 676 | pages = eabm4054 | date = December 2022 | pmid = 36542696 | doi = 10.1126/scitranslmed.abm4054 | hdl = 10044/1/101589 | hdl-access = free }}

Talarozole inhibits the metabolism of retinoic acid by blocking cytochrome P450 enzyme CYP26 isoenzymes (CYP26A1 and possibly also CYP26B1), retinoic acid hydroxylases.{{cite journal | vauthors = Nelson CH, Buttrick BR, Isoherranen N | title = Therapeutic potential of the inhibition of the retinoic acid hydroxylases CYP26A1 and CYP26B1 by xenobiotics | journal = Current Topics in Medicinal Chemistry | volume = 13 | issue = 12 | pages = 1402–1428 | year = 2013 | pmid = 23688132 | pmc = 4366427 | doi = 10.2174/1568026611313120004 }} Because of this mechanism, it is called a retinoic acid metabolism blocking agent (RAMBA).{{cite journal | vauthors = Giltaire S, Herphelin F, Frankart A, Hérin M, Stoppie P, Poumay Y | title = The CYP26 inhibitor R115866 potentiates the effects of all-trans retinoic acid on cultured human epidermal keratinocytes | journal = The British Journal of Dermatology | volume = 160 | issue = 3 | pages = 505–513 | date = March 2009 | pmid = 19120344 | doi = 10.1111/j.1365-2133.2008.08960.x | s2cid = 205258196 }}

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).{{cite journal | vauthors = Gomaa MS, Lim AS, Lau SC, Watts AM, Illingworth NA, Bridgens CE, Veal GJ, Redfern CP, Brancale A, Armstrong JL, Simons C | display-authors = 6 | title = Synthesis and CYP26A1 inhibitory activity of novel methyl 3-[4-(arylamino)phenyl]-3-(azole)-2,2-dimethylpropanoates | journal = Bioorganic & Medicinal Chemistry | volume = 20 | issue = 20 | pages = 6080–6088 | date = October 2012 | pmid = 22989911 | doi = 10.1016/j.bmc.2012.08.044 }}