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

General Information of Drug (ID: DMF29Q5)

• Drug Name: Connexyn Drug Info
• Synonyms: Estulic; Intuniv; Tenex; GUANFACINE HCL; Guanfacine hydrochloride; G 1043; LON 798; BS 100-141; Guanfacine hydrochloride [USAN:JAN]; SPD-503; Tenex (TN); BS-100-141; Guanfacine hydrochloride (JAN/USP); N-(Aminoiminomethyl)-2,6-dichlorobenzeneacetamide hydrochloride; N-(Aminoiminomethyl)-2,6-dichlorophenylacetamide monohydrochloride; N-(aminoiminomethyl)-2,6-dichloro-benzeneacetamide hydrochloride; N-Amidino-2-(2,6-dichlorophenyl)acetamide hydrochloride; N-Amidino-2-(2,6-dichlorophenyl)acetamide monohydrochloride; N-carbamimidoyl-2-(2,6-dichlorphenyl)acetamidhydrochlorid; N-(diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide hydrochloride; Benzeneacetamide, N-(aminoiminomethyl)-2,6-dichloro-, monohydrochloride; Benzeneacetamide, N-(aminoiminomethyl)-2,6-dichloro-, hydrochloride (1:1)

Indication

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[1]

• Cross-matching ID:
  PubChem CID: 71401
  ChEBI ID: CHEMBL1200494
  CAS Number: CAS 29110-48-3
  TTD Drug ID: DMF29Q5
  INTEDE Drug ID: DR0796

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]
Guanfacine	DMPN5IH	Attention deficit hyperactivity disorder	6A05.Z	Phase 4	[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) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]

Drug(s) Affected By Renin (REN)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[24]
Acebutolol	DM0TI4U	Hypertension	BA00-BA04	Approved	[25]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[26]
Reboxetine	DM26PRD	Depression	6A70-6A7Z	Approved	[27]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[28]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[29]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[30]
Naloxone	DM3FXMA	Narcotic depression	6A7Z	Approved	[31]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[32]
Chlorthalidone	DM4DMBT	Edema	MG29	Approved	[33]

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	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Renin (REN)	OT52GZR2	RENI_HUMAN	Gene/Protein Processing	[4]

References

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• [4] [Effect of 5-month guanfacine treatment on the renin-angiotensin-aldosterone system and some metabolic factors in patients with diabetes mellitus type II and hypertension]. Pol Tyg Lek. 1992 Nov 16-30;47(46-48):1045-7.
• [5] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
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• [7] Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13.
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• [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.
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• [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] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [16] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [17] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [18] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [19] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [20] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [23] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [24] Effects of histamine H2-receptor blockade on the cardiovascular reflex response to lower-body negative pressure in man. Acta Physiol Scand. 1990 May;139(1):161-72. doi: 10.1111/j.1748-1716.1990.tb08909.x.
• [25] Addition of acebutolol to diuretics in hypertension. Clin Pharmacol Ther. 1981 Dec;30(6):739-44. doi: 10.1038/clpt.1981.232.
• [26] Relative potency of a beta-blocking and a calcium entry blocking agent as antihypertensive drugs in black patients. Eur J Clin Pharmacol. 1986;29(5):523-7. doi: 10.1007/BF00635887.
• [27] Influences of norepinephrine transporter function on the distribution of sympathetic activity in humans. Hypertension. 2006 Jul;48(1):120-6. doi: 10.1161/01.HYP.0000225424.13138.5d. Epub 2006 May 22.
• [28] Effects of sulindac and naproxen on prostaglandin excretion in patients with impaired renal function and rheumatoid arthritis. Am J Med. 1990 Sep;89(3):313-21. doi: 10.1016/0002-9343(90)90344-d.
• [29] Effects of an angiotensin converting enzyme inhibitor, ramipril, on intracranial circulation in healthy volunteers. off. Br J Clin Pharmacol. 1992 Sep;34(3):224-30. doi: 10.1111/j.1365-2125.1992.tb04128.x.
• [30] Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites. Am J Physiol Renal Physiol. 2005 May;288(5):F1044-52. doi: 10.1152/ajprenal.00142.2004. Epub 2004 Dec 21.
• [31] beta-Endorphin and essential hypertension: importance of the clonidine-naloxone interaction. Acta Physiol Hung. 1985;65(2):217-26.
• [32] Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med. 1983 Dec 8;309(23):1414-9. doi: 10.1056/NEJM198312083092303.
• [33] Detection of low-renin hypertension; evaluation of out-patient renin-stimulating methods. Clin Sci Mol Med. 1975 Feb;48(2):91-6. doi: 10.1042/cs0480091.