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

General Information of Drug (ID: DMP2DNS)

• Drug Name: Rambazole Drug Info
• Synonyms: Talarozole; 201410-53-9; R-115866; N-(4-(2-ethyl-1-(1H-1,2,4-triazol-1-yl)butyl)phenyl)benzo[d]thiazol-2-amine; R115866; CHEMBL459505; C21H23N5S; Rambazole (TN); Talarozole (USAN/INN); Talarozole [USAN:INN]; R 115866; N-(4-(2-ethyl-1-(1H-1,2,4-triazol-1-yl)butyl)phenyl)-2-benzothiazolamine; Talarozole pound> SCHEMBL721201; CHEBI:102167; MolPort-018-666-712; SNFYYXUGUBUECJ-UHFFFAOYSA-N; BCP28256; BCP21218; BDBM50253810; 0328AB; AKOS005067289; DB13083; CS-1343; NCGC00378894-01; HY-14531; AX8224298; D09385; W-5674; MEN13510

Indication

Disease Entry	ICD 11	Status	REF
Psoriasis vulgaris	EA90	Phase 2	[1]
Asthma	CA23	Investigative	[2]

• Cross-matching ID:
  PubChem CID: 9799888
  ChEBI ID: CHEBI:102167
  CAS Number: CAS 201410-53-9
  TTD Drug ID: DMP2DNS

Molecule-Related Drug Atlas

Drug(s) Targeting Substance-K receptor (TACR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ibodutant	DMT67EH	Irritable bowel syndrome	DD91.0	Phase 3	[4]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[5]
Nepadutant	DMPMF6L	Infantile colics	DD93.1	Phase 1/2	[6]
Saredutant	DMSRJY3	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[7]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[8]
FK-224	DM1JUS0	Asthma	CA23	Discontinued in Phase 2	[9]
DNK-333	DM4ZO01	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[10]
AVE-5883	DM3P84V	Asthma	CA23	Discontinued in Phase 1/2	[11]
UK-224671	DMDTRJB	Urinary incontinence	MF50.2	Discontinued in Phase 1	[12]
SR 144190	DMK4XT8	Acute or chronic pain	MG30-MG31	Discontinued in Phase 1	[13]

Drug(s) Targeting Cytochrome P450 26 (CYP26A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LIAROZOLE	DM4OYXE	Dermatological disease	DA24.Y	Phase 2/3	[14]
4-((+/-)-(1H-imidazol-1-yl)-(E)-methylretinoate	DMI15VQ	Discovery agent	N.A.	Investigative	[15]
4-((+/-)-(1H-imidazol-1-yl)-(E)-retinoic acid	DMKYB4D	Discovery agent	N.A.	Investigative	[15]

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	[16]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[17]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[16]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[18]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[20]
Dolutegravir	DMCZGRE	Human immunodeficiency virus infection	1C62	Approved	[21]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[16]
Diethylstilbestrol	DMN3UXQ	Gonorrheal vaginitis	GA02	Approved	[22]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cytochrome P450 26 (CYP26A1)	TTD7Q0R	CP26A_HUMAN	Inhibitor	[1]
Substance-K receptor (TACR2)	TTYO0A3	NK2R_HUMAN	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 26A1 (CYP26A1)	OTL1DFWV	CP26A_HUMAN	Gene/Protein Processing	[3]

References

• [1] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [2] Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor. Eur J Pharmacol. 2005 Jun 1;516(2):104-11.
• [3] Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in the elimination of active retinoids. Mol Pharmacol. 2015;87(3):430-41.
• [4] Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi. Eur J Pharmacol. 2013 Nov 15;720(1-3):180-5.
• [5] Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
• [6] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [7] Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3. Biochem Pharmacol. 2009 May 1;77(9):1522-30.
• [8] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [9] Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerv... J Pharmacol Exp Ther. 1992 Jul;262(1):403-8.
• [10] Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients. Eur Respir J. 2004 Jan;23(1):76-81.
• [11] Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma. Am J Respir Crit Care Med. 2007 Mar 1;175(5):450-7.
• [12] Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42.
• [13] Pharmacologic evaluation of neurokinin-2 receptor antagonists in the guinea pig respiratory tract. Am J Vet Res. 2004 Jul;65(7):984-91.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Beta-Carotene conversion into vitamin A in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3562-9.
• [18] Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
• [19] 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.
• [20] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [21] 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.
• [22] 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.
• [23] 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.