TALAROZOLE

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H23N5S
Molecular Weight	377.506
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC(CC)C(N1C=NC=N1)C2=CC=C(NC3=NC4=C(S3)C=CC=C4)C=C2

InChI

InChIKey=SNFYYXUGUBUECJ-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21228620
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19120344

Talarozole (formerly R115866) is a new highly potent and selective azole derivative, which inhibits cytochrome-P450-dependent all-trans-retinoic acid catabolism by blocking the cytochrome P450 enzyme isoform CYP26, a retinoic acid hydroxylase. It is in clinical development for the treatment of psoriasis and acne. However, no local pharmacokinetic data on the diffusion behaviour of talarozole in the skin itself are available. As topical application might be an interesting alternative to oral therapy because of the reduced systemic side effects. The distribution of talarozole within the skin was investigated: 80% was located in the epidermis, while the remaining 20% was found in the dermis. The epidermal concentration of talarozole achieved after a single topical application was sufficiently high to enable the potential induction of local retinoid-like effects.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 26A1 6 Target ID: CHEMBL5141 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19120344	Inhibitor 8297		4.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acne 98 Sources: https://clinicaltrials.gov/ct2/show/NCT00725439	Palliative		Phase II 1132	Unknown Approved Use Unknown
Psoriasis 84 Sources: https://clinicaltrials.gov/ct2/show/NCT00725348	Palliative		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
80.3 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28446509	2.5 mg/kg single, oral dose: 2.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		TALAROZOLE plasma	Mus musculus population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
190 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28446509	2.5 mg/kg single, oral dose: 2.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		TALAROZOLE plasma	Mus musculus population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28446509	2.5 mg/kg single, oral dose: 2.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		TALAROZOLE plasma	Mus musculus population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
5.8% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28446509	2.5 mg/kg single, oral dose: 2.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		TALAROZOLE plasma	Mus musculus population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP26A1 1 CYP26B1 1 CYP19 1 P-gp 1461 CYP26 1		CYP26B1 1 CYP26A1 1

Drug as perpetrator

Target	Modality	Activity
CYP26B1 1	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/28446509/ \| https://pubmed.ncbi.nlm.nih.gov/26918322/	yes [IC50 0.0005 uM]
CYP26 1	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10734183/ \| https://pubmed.ncbi.nlm.nih.gov/23688132/	yes [IC50 0.004 uM]
CYP26A1 1	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/28446509/ \| https://pubmed.ncbi.nlm.nih.gov/23688132/	yes [IC50 0.0051 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681437	yes [IC50 0.2684 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681437	yes [IC50 0.9522 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681437	yes [IC50 2.3919 uM]
CYP19 2	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10734183/	yes [IC50 2.6 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678261	yes [IC50 23.1093 uM]
CYP26A1 1	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/19016711/	yes
CYP26B1 1	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/19016711/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY537802	https://www.001chemical.com/chem/201410-53-9
001 Chemical	DY576109	https://www.001chemical.com/chem/870093-23-5
AA Blocks	AA002DAT	https://www.aablocks.com/goods/Goods/detail?id=AA002DAT
AK Scientific, Inc. (AKSCI)	0328AB	http://www.aksci.com/item_detail.php?cat=0328AB
Aaron Chemicals	AR002E2L	http://www.aaronchem.com/201410-53-9
Achemtek	0102-013184	http://www.achemtek.com/201410-53-9
Ambinter	Amb22235488	http://www.ambinter.com/reference/22235488
Aurora Fine Chemicals LLC	A30.258.839	http://online.aurorafinechemicals.com/info?ID=A30.258.839
Aurum Pharmatech LLC	W-5674	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5674
AvaChem Scientific	3629	http://www.avachem.com/productSearch.asp?3629
BLD Pharm	BD224298	http://www.bldpharm.com/products/201410-53-9.html
BLD Pharm	BD01139584	http://www.bldpharm.com/products/201410-66-4.html
BOC Sciences	201410-53-9	https://www.bocsci.com/product/talarozole-cas-201410-53-9-458817.html
BOC Sciences	870093-23-5	https://www.bocsci.com/talarozole-cas-870093-23-5-item-99547.html
BioChemPartner	BCP28256	http://www.biochempartner.com/201410-53-9-BCP28256
BioChemPartner	BCP21218	http://www.biochempartner.com/870093-23-5-BCP21218
BioCrick	BCC1980	http://www.biocrick.com/Talarozole-BCC1980.html
CSNpharm	CSN12919	https://www.csnpharm.com/products/talarozole.html
Chem Scene	CS-1343	http://www.chemscene.com/201410-53-9.html
ChemShuttle	150594	http://www.chemshuttle.com/catalogsearch/result/?q=201410-53-9&cat=
Chemspace	CSSB00020629329	https://chem-space.com/CSSB00020629329
Clearsynth	CS-T-86935	https://www.clearsynth.com/en/CST86935.html
DC Chemicals	DC9413	http://www.dcchemicals.com/product_show-Talarozole.html
Lab Network	LN01342021	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342021
MedChem Express	HY-14531	https://www.medchemexpress.com/Talarozole.html
MolPort	MolPort-018-666-712	https://www.molport.com/shop/molecule-link/MolPort-018-666-712
Molcore	MC537802	https://www.molcore.com/product/201410-53-9
Molcore	MC576109	https://www.molcore.com/product/870093-23-5
MuseChem	I002545	https://www.musechem.com/product/I002545.html
eNovation Chemicals	D552113	https://www.enovationchem.com/ProductDetails.asp?ProductID=D552113
eNovation Chemicals	D674344	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674344
eNovation Chemicals	D679421	https://www.enovationchem.com/ProductDetails.asp?ProductID=D679421
eNovation Chemicals	D768645	https://www.enovationchem.com/ProductDetails.asp?ProductID=D768645
iChemical	EBD2210106	http://www.ichemical.com/products/201410-53-9.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor.	2005 Jun 1	15925360
Cyp26 genes a1, b1 and c1 are down-regulated in Tbx1 null mice and inhibition of Cyp26 enzyme function produces a phenocopy of DiGeorge Syndrome in the chick.	2006 Dec 1	17047027
Retinoic acid regulates sex-specific timing of meiotic initiation in mice.	2006 Feb 21	16461896
Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development.	2007 Jan	17164423
CYP26 inhibitor R115866 increases retinoid signaling in intimal smooth muscle cells.	2007 Jul	17510468
Gateways to clinical trials.	2008 Jun	18806898
Talarozole, a selective inhibitor of P450-mediated all-trans retinoic acid for the treatment of psoriasis and acne.	2008 Nov	18951302
Both all-trans retinoic acid and cytochrome P450 (CYP26) inhibitors affect the expression of vitamin A metabolizing enzymes and retinoid biomarkers in organotypic epidermis.	2009 Aug	19294396
Topical treatment with CYP26 inhibitor talarozole (R115866) dose dependently alters the expression of retinoid-regulated genes in normal human epidermis.	2009 Jan	19016711
The involvement of cytochrome p450 (CYP) 26 in the retinoic acid metabolism of human epidermal keratinocytes.	2009 Mar	19171200
CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats.	2010 Nov	20580668
CYP26B1 plays a major role in the regulation of all-trans-retinoic acid metabolism and signaling in human aortic smooth muscle cells.	2011	20606468
Small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26): synthesis and biological evaluation of imidazole methyl 3-(4-(aryl-2-ylamino)phenyl)propanoates.	2011 Apr 28	21428449
Synthesis and biological evaluation of 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propyl derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26).	2011 Oct 13	21838328

Patents

Sample Use Guides

In Vivo Use Guide

1.0 mg once daily

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

TALAROZOLE

Official Name

English

R-115866

Code

English

R115866

Code

English

talarozole [INN]

Common Name

English

TALAROZOLE [USAN]

Common Name

English

N-[4-[(1RS)-2-Ethyl-1-(1H-1,2,4-triazol-1-yl)butyl]phenyl]benzothiazol-2-amine

Systematic Name

English

Talarozole [WHO-DD]

Common Name

English

RAMBAZOLE

Brand Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

365412