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

General Information of Drug (ID: DMMHSLC)

• Drug Name: Afq056 Drug Info
• Synonyms: Mavoglurant

Indication

Disease Entry	ICD 11	Status	REF
Fragile X syndrome	LD55	Phase 2/3	[1] , [2]

• Cross-matching ID:
  PubChem CID: 9926832
  CAS Number: CAS 543906-09-8
  TTD Drug ID: DMMHSLC
  INTEDE Drug ID: DR1870

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 1A1 (CYP1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Premature labour	JB00	Approved	[5]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[6]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[7]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[8]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[9]
Diclofenac	DMPIHLS	Osteoarthritis	FA00-FA05	Approved	[10]
Estrone	DM5T6US	Menopausal and postmenopausal disorder	GA30	Approved	[11]
Erythromycin	DM4K7GQ	Bacterial infection	1A00-1C4Z	Approved	[12]
Riboflavin	DM8YMWE	Acne vulgaris	ED80	Approved	[13]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[14]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ADX-48621	DM6GTMD	Parkinson disease	8A00.0	Phase 2/3	[15]
RG-7090	DMX8JYN	Fragile X syndrome	LD55	Phase 2	[16]
STX-107	DMLNKX7	Autism spectrum disorder	6A02	Phase 2	[17]
ADX10059	DMGVKHQ	Anxiety disorder	6B00-6B0Z	Phase 2	[18]
McN3377	DMTCADJ	Fragile X syndrome	LD55	Phase 1/2	[19]
MK-3328	DMW2O5D	Alzheimer disease	8A20	Phase 1	[20]
[3H]fenobam	DMBOXA1	Allodynia	MB40.1	Phase 1	[21]
RG7342	DMIW5NG	Schizophrenia	6A20	Phase 1	[22]
Tetra-hydro-oxazolopyridine derivative 2	DMP65Z4	N. A.	N. A.	Patented	[23]
Tetra-hydro-oxazolopyridine derivative 1	DM72MDA	N. A.	N. A.	Patented	[23]

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	Modulator	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A1 (CYP1A1) Main DME	DE6OQ3W	CP1A1_HUMAN	Substrate	[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: 7586).
• [2] ClinicalTrials.gov (NCT01433354) Long-term, Safety and Tolerability Study of AFQ056 in Adolescent Patients With Fragile X Syndrome (Open-label). U.S. National Institutes of Health.
• [3] 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.
• [4] Methods to Assess Pulmonary Metabolism.
• [5] Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics. 2000 Aug;10(6):519-30.
• [6] Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74.
• [7] Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94.
• [8] Preferred orientations in the binding of 4'-hydroxyacetanilide (acetaminophen) to cytochrome P450 1A1 and 2B1 isoforms as determined by 13C- and 15N-NMR relaxation studies. J Med Chem. 1994 Mar 18;37(6):860-7.
• [9] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [10] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [11] A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio. Clin Chem Lab Med. 2005;43(7):702-6.
• [12] Cytochromes P450 in crustacea. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Nov;121(1-3):157-72.
• [13] Disruption of endogenous regulator homeostasis underlies the mechanism of rat CYP1A1 mRNA induction by metyrapone. Biochem J. 1998 Apr 1;331 ( Pt 1):273-81.
• [14] Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr Drug Metab. 2007 Aug;8(6):554-62.
• [15] Pipeline of Addex Pharma. Addex Pharma. 2009.
• [16] The challenges of clinical trials in fragile X syndrome. Psychopharmacology (Berl) 2014; 231(6): 1237-1250.
• [17] 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.
• [18] 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.
• [19] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [20] 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).
• [21] 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.
• [22] Clinical pipeline report, company report or official report of Roche.
• [23] mGlu5 negative allosteric modulators: a patent review (2013 - 2016).Expert Opin Ther Pat. 2017 Jun;27(6):691-706.