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

General Information of Drug (ID: DMAVBKP)

• Drug Name: SIB-1893 Drug Info
• Synonyms: SIB 1893; SIB-1893; 2-methyl-6-(2-phenylethenyl)pyridine; 6266-99-5; SIB1893; 2-methyl-6-[(E)-2-phenylethenyl]pyridine; 7370-21-0; CHEMBL88612; MLS002607995; (E)-2-methyl-6-styrylpyridine; [E]-2-Methyl-6-[2-phenylethenyl]pyridine; (E)-2-Methyl-6-[2-phenylethenyl]pyridine; SR-01000076143; Lopac0_001171; Pyridine,2-methyl-6-(2-phenylethenyl)-; AC1NSKMI; AC1Q4VO3; GTPL1432; CHEBI:93178; BDBM86715; MolPort-003-959-634; HMS3263L03; ZINC3941522; 2-[(E)-Styryl]-6-methylpyridine; NSC36665; SIB 1893, >99%, solid; Tox21_501171

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 5311432
  ChEBI ID: CHEBI:93178
  CAS Number: CAS 6266-99-5
  TTD Drug ID: DMAVBKP

Molecule-Related Drug Atlas

Drug(s) Targeting Metabotropic glutamate receptor 5 (mGluR5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AFQ056	DMMHSLC	Fragile X syndrome	LD55	Phase 2/3	[4]
ADX-48621	DM6GTMD	Parkinson disease	8A00.0	Phase 2/3	[5]
RG-7090	DMX8JYN	Fragile X syndrome	LD55	Phase 2	[6]
STX-107	DMLNKX7	Autism spectrum disorder	6A02	Phase 2	[7]
ADX10059	DMGVKHQ	Anxiety disorder	6B00-6B0Z	Phase 2	[8]
McN3377	DMTCADJ	Fragile X syndrome	LD55	Phase 1/2	[9]
MK-3328	DMW2O5D	Alzheimer disease	8A20	Phase 1	[10]
[3H]fenobam	DMBOXA1	Allodynia	MB40.1	Phase 1	[11]
RG7342	DMIW5NG	Schizophrenia	6A20	Phase 1	[12]
BMS-984923	DMFNDUL	Alzheimer disease	8A20	Phase 1	[13]

Drug(s) Affected By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[14]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[14]
Etoricoxib	DM6A4NW	Rheumatoid arthritis	FA20	Approved	[14]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[15]
Hesperetin	DMKER83	High blood cholesterol level	5C80.00	Approved	[16]
Stiripentol	DMMSDOY	Dravet syndrome	8A61.11	Approved	[17]
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[18]
Zileuton	DMVRIC2	Allergic asthma	CA23.0	Approved	[19]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[20]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[21]

Drug(s) Affected By Cytochrome P450 1B1 (CYP1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flutamide	DMK0O7U	Prostate cancer	2C82.0	Approved	[22]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[24]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[25]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[26]
Melatonin	DMKWFBT	Depression	6A70-6A7Z	Approved	[27]
Vitamin A	DMJ2AH4	Night blindness	9D45	Approved	[28]
Amodiaquine	DME4RA8	Malaria	1F40-1F45	Approved	[29]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[30]
Pantothenic acid	DM091H2	Vitamin deficiency	5B55-5B71	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Metabotropic glutamate receptor 5 (mGluR5)	TTHS256	GRM5_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Gene/Protein Processing	[3]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Gene/Protein Processing	[3]

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: 1432).
• [2] Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3371-5.
• [3] Inhibition of human hepatic CYP isoforms by mGluR5 antagonists. Life Sci. 2004 Jul 9;75(8):947-53.
• [4] Metabolism and disposition of the metabotropic glutamate receptor 5 antagonist (mGluR5) mavoglurant (AFQ056) in healthy subjects. Drug Metab Dispos. 2013 Sep;41(9):1626-41.
• [5] Pipeline of Addex Pharma. Addex Pharma. 2009.
• [6] The challenges of clinical trials in fragile X syndrome. Psychopharmacology (Berl) 2014; 231(6): 1237-1250.
• [7] Social Communication is an Emerging Target for Pharmacotherapy in Autism Spectrum Disorder - A Review of the Literature on Potential Agents. J Can Acad Child Adolesc Psychiatry. 2014 February; 23(1):20-30.
• [8] A proof-of-concept study evaluating the effect of ADX10059, a metabotropic glutamate receptor-5 negative allosteric modulator, on acid exposure and... Gut. 2009 Sep;58(9):1192-9.
• [9] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [10] 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. (Target id: 293).
• [11] Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agon... J Pharmacol Exp Ther. 2005 Nov;315(2):711-21.
• [12] Clinical pipeline report, company report or official report of Roche.
• [13] Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer's Mouse Phenotypes. Cell Rep. 2017 Jul 5;20(1):76-88.
• [14] In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):157-65.
• [15] Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
• [16] Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
• [17] Stiripentol. Expert Opin Investig Drugs. 2005 Jul;14(7):905-11.
• [18] Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
• [19] Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
• [20] Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15.
• [21] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [22] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [23] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [24] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [25] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [26] In vitro aromatic bioactivation of the weak estrogen E(2)alpha and genesis of DNA adducts. Steroids. 2005 Mar;70(3):161-72. doi: 10.1016/j.steroids.2004.11.004.
• [27] Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005 Apr;33(4):489-94.
• [28] Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Drug Metab Dispos. 2004 Aug;32(8):840-7.
• [29] Apoptosis contributes to the cytotoxicity induced by amodiaquine and its major metabolite N-desethylamodiaquine in hepatic cells. Toxicol In Vitro. 2020 Feb;62:104669. doi: 10.1016/j.tiv.2019.104669. Epub 2019 Oct 16.
• [30] Genetic variants contributing to daunorubicin-induced cytotoxicity. Cancer Res. 2008 May 1;68(9):3161-8. doi: 10.1158/0008-5472.CAN-07-6381.
• [31] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.