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

General Information of Drug (ID: DMCOZJY)

• Drug Name: Tenapanor Drug Info
• Synonyms: 1234423-95-0; UNII-WYD79216A6; AZD 1722; WYD79216A6; AZD-1722; 3-((S)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(26-((3-((S)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)sulfonamido)-10,17-dioxo-3,6,21,24-tetraoxa-9,11,16,18-tetraazahexacosyl)benzenesulfonamide; Tenapanor [USAN:INN]; Tenapanor(free base); GTPL8449; CHEMBL3304485; SCHEMBL15267600; DTXSID40154016; BCP24892; BCP28554; EX-A2506

Indication

Disease Entry	ICD 11	Status	REF
Irritable bowel syndrome	DD91.0	Approved	[1]
Constipation	DD91.1	Phase 2	[2]
Kidney disease	GC2Z	Phase 2	[3]

• Cross-matching ID:
  PubChem CID: 71587953
  CAS Number: CAS 1234423-95-0
  TTD Drug ID: DMCOZJY
  INTEDE Drug ID: DR1549
  ACDINA Drug ID: D01472

Molecule-Related Drug Atlas

Drug(s) Targeting Sodium/hydrogen exchanger 3 (SLC9A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AVE-0657	DMESMHU	Cheyne-stokes respiration	MD11.Y	Phase 2	[5]
AZD1772//RDX5791	DMX5SG7	Chronic kidney disease	GB61	Phase 2	[6]
CARIPORIDE	DMV2DY3	Angina pectoris	BA40	Discontinued in Phase 2	[7]
ENIPORIDE	DME7OCX	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[7]
HOE-694	DML0B97	Heart arrhythmia	BC65	Terminated	[8]
N-(3-Methanesulfonyl-4-methyl-benzoyl)-guanidine	DMSVQJP	Discovery agent	N.A.	Investigative	[8]
N-(4-Chloro-3-methanesulfonyl-benzoyl)-guanidine	DMFG6MU	Discovery agent	N.A.	Investigative	[8]
N-(4-Cyano-3-methanesulfonyl-benzoyl)-guanidine	DMGI9EA	Discovery agent	N.A.	Investigative	[8]
N-(4-Bromo-3-methanesulfonyl-benzoyl)-guanidine	DMC28SN	Discovery agent	N.A.	Investigative	[8]
N-(3-Methanesulfonyl-4-methoxy-benzoyl)-guanidine	DM0H8CK	Discovery agent	N.A.	Investigative	[8]

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	[9]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[10]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[11]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[12]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[13]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[15]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[16]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[10]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[17]

Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[18]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[20]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[21]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[22]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[23]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[25]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[26]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sodium/hydrogen exchanger 3 (SLC9A3)	TTFZVPO	SL9A3_HUMAN	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 3A5 (CYP3A5) Main DME	DEIBDNY	CP3A5_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] ClinicalTrials.gov (NCT01340053) A Study to Evaluate the Safety and Efficacy of RDX5791 for the Treatment of Constipation Predominant Irritable Bowel Syndrome (IBS-C). U.S. National Institutes of Health.
• [3] ClinicalTrials.gov (NCT01764854) Pharmacodynamic Study of AZD1722 in End-stage Renal Disease Patients on Hemodialysis. U.S. National Institutes of Health.
• [4] FDA label of Tenapanor. The 2020 official website of the U.S. Food and Drug Administration.
• [5] Inhibition of central Na(+)/H(+) exchanger type 3 can alleviate sleep apnea in Sprague-Dawley rats. Chin Med J (Engl). 2014;127(1):48-53.
• [6] RDX5791, a First-in-Class Minimally Systemic NHE3 Inhibitor in Clinical Development for CIC and IBS-C, Increases Intestinal Sodium Leading to Enhanced Intestinal Fluid Volume and Transit. Gastroenterology. 2011;140(suppl 1):S99.
• [7] Bicyclic acylguanidine Na+/H+ antiporter inhibitors. J Med Chem. 1998 Sep 10;41(19):3736-47.
• [8] (2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na+/H+ antiporter inhibitors. J Med Chem. 1997 Jun 20;40(13):2017-34.
• [9] 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.
• [10] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [11] 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.
• [12] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [13] 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.
• [14] 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.
• [15] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [16] 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.
• [17] 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.
• [18] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
• [19] Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
• [20] Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
• [21] Drug Interactions Flockhart Table
• [22] Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
• [23] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [24] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [25] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [26] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.