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

General Information of Drug (ID: DMPN5IH)

• Drug Name: Guanfacine Drug Info
• Synonyms: GUANFACINE; Tenex; Guanfacinum [INN-Latin]; Guanfacina [INN-Spanish]; Estulic; Intuniv; N-amidino-2-(2,6-dichlorophenyl)acetamide; CHEBI:5558; INJOMKTZOLKMBF-UHFFFAOYSA-N; SPD 503; C9H9Cl2N3O; N-carbamimidoyl-2-(2,6-dichlorophenyl)acetamide; N-(diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide; Guanfacine Monohydrochloride; NCGC00015469-05; Lon798; Guanfacine (INN); Estulic (TN); Tenex (Salt/Mix); Estulic (Salt/Mix); Tocris-1030; Prestwick1_000339; Prestwick3_000339; Prestwick2_000339; Prestwick0_000339; Lopac-G-1043

Indication

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[1]
Alzheimer disease	8A20	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 3519
  ChEBI ID: CHEBI:5558
  CAS Number: CAS 29110-47-2
  TTD Drug ID: DMPN5IH
  VARIDT Drug ID: DR01628

Molecule-Related Drug Atlas

Drug(s) Targeting Adrenergic receptor alpha-2A (ADRA2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lofexidine	DM1WXA6	Heroin and opiate withdrawal	6C43	Approved	[5]
MOXONIDINE	DMGFB0E	Alcohol dependence	6C40.2	Approved	[6]
Connexyn	DMF29Q5	Attention deficit hyperactivity disorder	6A05.Z	Approved	[7]
A295	DM55GO2	Aggressive cancer	2A00-2F9Z	IND submitted	[8]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[9]
DSP-1200	DM4WSHG	Depression	6A70-6A7Z	Phase 1	[10]
MAZAPERTINE	DMRHYAU	N. A.	N. A.	Discontinued in Phase 2	[11]
NMI-870	DMU596F	Sexual dysfunction	HA00-HA01	Discontinued in Phase 2	[12]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[13]
A-80426	DMBC3DG	N. A.	N. A.	Terminated	[14]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[15]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[16]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[17]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[18]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-2A (ADRA2A)	TTWG9A4	ADA2A_HUMAN	Agonist	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

References

• [1] Guanfacine FDA Label
• [2] ClinicalTrials.gov (NCT03116126) Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease. U.S.National Institutes of Health.
• [3] Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13.
• [4] An in vitro evaluation of guanfacine as a substrate for P-glycoprotein. Neuropsychiatr Dis Treat. 2011;7:501-5.
• [5] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [6] Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5.
• [7] alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009 Sep 29;163(1):339-51.
• [8] Clinical pipeline report, company report or official report of Klus Pharma
• [9] A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem. 1994 Apr 15;37(8):1060-2.
• [12] Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges. Cardiovasc Hematol Agents Med Chem. 2009 October; 7(4): 260-269.
• [13] Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.
• [14] Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71.
• [15] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [16] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [17] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [18] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [19] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [20] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [21] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.