Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM4OYXE)

• Drug Name: LIAROZOLE Drug Info
• Synonyms: Liarozole; Liazal; 115575-11-6; R-75251; LIAROZOLE FUMARATE; Liarozole [INN:BAN]; Liarozolum [INN-Latin]; Liarozol [INN-Spanish]; R 75251; R-61405; R085246; R 61405; R-085246; R 085246; 6-((3-chlorophenyl)(1H-imidazol-1-yl)methyl)-1H-benzo[d]imidazole; UNII-17NYD2210B; CHEMBL389433; UNII-090Y06W08H; 17NYD2210B; 090Y06W08H; Liarozolum; Liarozol; 1H-Benzimidazole, 5-((3-chlorophenyl)-1H-imidazol-1-ylmethyl)-; NCGC00181034-01; Liarozole, (-)-; Liarozole, (+)-; AC1L1TNN; AC1Q3M3B; SCHEMBL18597; GTPL5210; SCHEMBL15944205; DTXSID9048277

Indication

Disease Entry	ICD 11	Status	REF
Dermatological disease	DA24.Y	Phase 2/3	[1]

• Cross-matching ID:
  PubChem CID: 60652
  ChEBI ID: CHEBI:135316
  CAS Number: CAS 115575-11-6
  TTD Drug ID: DM4OYXE

Molecule-Related Drug Atlas

Drug(s) Targeting Aromatase (CYP19A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anastrozole	DMNP60F	Breast cancer	2C60-2C65	Approved	[5]
Letrozole	DMH07Y3	Estrogen-receptor positive breast cancer		Approved	[6]
Exemestane	DM9HPW3	Hormonally-responsive breast cancer	2C60-2C65	Approved	[6]
Aminoglutethimide	DMWFHMZ	Cushing disease	5A70	Approved	[7]
FADROZOLE	DM3C5GZ	Breast cancer	2C60-2C65	Approved	[8]
Testolactone	DMVY4GN	Breast cancer	2C60-2C65	Approved	[9]
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[10]
BGS-649	DMO4MNQ	Endometriosis	GA10	Phase 2	[11]
NARINGENIN	DMHAZLM	N. A.	N. A.	Phase 1	[2]
FORMESTANE	DMWIDJK	Breast cancer	2C60-2C65	Withdrawn from market	[12]

Drug(s) Targeting Cytochrome P450 26 (CYP26A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rambazole	DMP2DNS	Psoriasis vulgaris	EA90	Phase 2	[13]
4-((+/-)-(1H-imidazol-1-yl)-(E)-methylretinoate	DMI15VQ	Discovery agent	N.A.	Investigative	[14]
4-((+/-)-(1H-imidazol-1-yl)-(E)-retinoic acid	DMKYB4D	Discovery agent	N.A.	Investigative	[14]

Drug(s) Affected By Cytochrome P450 26A1 (CYP26A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vitamin A	DMJ2AH4	Night blindness	9D45	Approved	[15]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[16]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[15]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]
Dolutegravir	DMCZGRE	Human immunodeficiency virus infection	1C62	Approved	[20]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[15]
Diethylstilbestrol	DMN3UXQ	Gonorrheal vaginitis	GA02	Approved	[21]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[2]
Cytochrome P450 26 (CYP26A1)	TTD7Q0R	CP26A_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 26A1 (CYP26A1)	OTL1DFWV	CP26A_HUMAN	Gene/Protein Processing	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5210).
• [2] Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
• [3] Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorg Med Chem. 2008 Sep 1;16(17):8301-13.
• [4] Discovery of inhibitors of MCF-7 tumor cell adhesion to endothelial cells and investigation on their mode of action. Arch Pharm (Weinheim). 2004 Dec;337(12):687-94. doi: 10.1002/ardp.200400622.
• [5] Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:945-8.
• [6] Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
• [7] Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis. Chem Res Toxicol. 2007 Jul;20(7):1038-45.
• [8] Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. J Med Chem. 2005 Nov 17;48(23):7282-9.
• [9] Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9.
• [10] Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template. J Med Chem. 2010 Mar 11;53(5):2155-70.
• [11] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032111)
• [12] The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
• [13] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [14] Novel retinoic acid metabolism blocking agents endowed with multiple biological activities are efficient growth inhibitors of human breast and pros... J Med Chem. 2004 Dec 30;47(27):6716-29.
• [15] Regulation of a highly specific retinoic acid-4-hydroxylase (CYP26A1) enzyme and all-trans-retinoic acid metabolism in human intestinal, liver, endothelial, and acute promyelocytic leukemia cells. Leuk Lymphoma. 2005 Oct;46(10):1497-506.
• [16] Beta-Carotene conversion into vitamin A in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3562-9.
• [17] Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
• [18] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [19] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [20] Dolutegravir Impairs Stem Cell-Based 3D Morphogenesis Models in a Manner Dependent on Dose and Timing of Exposure: An Implication for Its Developmental Toxicity. Toxicol Sci. 2021 Nov 24;184(2):191-203. doi: 10.1093/toxsci/kfab112.
• [21] Estrogen receptor alpha (ER)-mediated coregulator binding and gene expression discriminates the toxic ER agonist diethylstilbestrol (DES) from the endogenous ER agonist 17-estradiol (E2). Cell Biol Toxicol. 2020 Oct;36(5):417-435. doi: 10.1007/s10565-020-09516-6. Epub 2020 Feb 22.
• [22] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.