TENAPANOR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C50H66Cl4N8O10S2
Molecular Weight	1145.049
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C[C@@H](C2=CC=CC(=C2)S(=O)(=O)NCCOCCOCCNC(=O)NCCCCNC(=O)NCCOCCOCCNS(=O)(=O)C3=CC(=CC=C3)[C@@H]4CN(C)CC5=C4C=C(Cl)C=C5Cl)C6=C(C1)C(Cl)=CC(Cl)=C6

InChI

InChIKey=DNHPDWGIXIMXSA-CXNSMIOJSA-N

InChI=1S/C50H66Cl4N8O10S2/c1-61-31-43(41-27-37(51)29-47(53)45(41)33-61)35-7-5-9-39(25-35)73(65,66)59-15-19-71-23-21-69-17-13-57-49(63)55-11-3-4-12-56-50(64)58-14-18-70-22-24-72-20-16-60-74(67,68)40-10-6-8-36(26-40)44-32-62(2)34-46-42(44)28-38(52)30-48(46)54/h5-10,25-30,43-44,59-60H,3-4,11-24,31-34H2,1-2H3,(H2,55,57,63)(H2,56,58,64)/t43-,44-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30846557 | https://www.prnewswire.com/news-releases/ardelyx-submits-new-drug-application-for-us-marketing-authorization-of-tenapanor-for-ibs-c-to-us-food-and-drug-administration-300711834.html

Tenapanor is an inhibitor of the sodium-proton (Na(+)/H(+)) exchanger NHE3 and reduces sodium absorption in the GI tract, thus increasing intestinal fluid. Ardelyx has completed Phase 3 development of tenapanor for the treatment of irritable bowel syndrome with constipation (IBS-C) and submitted a new drug application to the U.S. Food and Drug Administration for the treatment of patients with IBS-C. In addition, tenapanor successfully completed phase III clinical trial for the treatment of hyperphosphatemia in people with end-stage renal disease who are on dialysis and RDX013, a potassium secretagogue program for the potential treatment of high potassium, or hyperkalemia, a problem among certain patients with kidney and/or heart disease.

Originator

Approval Year

Doses

Dose	Population	Adverse events
50 mg 2 times / day multiple, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf	unhealthy, adult n = 1203 Health Status: unhealthy Condition: IBS-C Age Group: adult Sex: unknown Population Size: 1203 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (6.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf
90 mg 2 times / day steady, oral Highest studied dose Dose: 90 mg, 2 times / day Route: oral Route: steady Dose: 90 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	healthy, mean 29.3 years n = 12 Health Status: healthy Age Group: mean 29.3 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	Other AEs: Diarrhea, Abdominal pain... Other AEs: Diarrhea (3 patients) Abdominal pain (1 patient) Headache (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/
180 mg single, oral Highest studied dose Dose: 180 mg Route: oral Route: single Dose: 180 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	healthy, mean 37.5 years n = 6 Health Status: healthy Age Group: mean 37.5 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/
60 mg 2 times / day steady, oral Highest studied dose Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	healthy, mean 37.5 years n = 12 Health Status: healthy Age Group: mean 37.5 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	Other AEs: Diarrhea... Other AEs: Diarrhea (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/
50 mg 2 times / day multiple, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31934897/	unhealthy, mean 45 years n = 307 Health Status: unhealthy Condition: IBS-C Age Group: mean 45 years Sex: M+F Population Size: 307 Sources: https://pubmed.ncbi.nlm.nih.gov/31934897/	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (6.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/31934897/

AEs

AE	Significance	Dose	Population
Diarrhea	6.5% Disc. AE	50 mg 2 times / day multiple, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf	unhealthy, adult n = 1203 Health Status: unhealthy Condition: IBS-C Age Group: adult Sex: unknown Population Size: 1203 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf
Abdominal pain	1 patient	90 mg 2 times / day steady, oral Highest studied dose Dose: 90 mg, 2 times / day Route: oral Route: steady Dose: 90 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	healthy, mean 29.3 years n = 12 Health Status: healthy Age Group: mean 29.3 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/
Headache	1 patient	90 mg 2 times / day steady, oral Highest studied dose Dose: 90 mg, 2 times / day Route: oral Route: steady Dose: 90 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	healthy, mean 29.3 years n = 12 Health Status: healthy Age Group: mean 29.3 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/
Diarrhea	3 patients	90 mg 2 times / day steady, oral Highest studied dose Dose: 90 mg, 2 times / day Route: oral Route: steady Dose: 90 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	healthy, mean 29.3 years n = 12 Health Status: healthy Age Group: mean 29.3 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/
Diarrhea	1 patient	60 mg 2 times / day steady, oral Highest studied dose Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/	healthy, mean 37.5 years n = 12 Health Status: healthy Age Group: mean 37.5 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/27368672/
Diarrhea	6.5% Disc. AE	50 mg 2 times / day multiple, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31934897/	unhealthy, mean 45 years n = 307 Health Status: unhealthy Condition: IBS-C Age Group: mean 45 years Sex: M+F Population Size: 307 Sources: https://pubmed.ncbi.nlm.nih.gov/31934897/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 Cav1.2 45 CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT2 647 MATE1 306 MATE2 263 CYP3A4/5 278	BCRP 561 OATP1B1 406 OATP1B3 350 CYP3A5 395 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667	CYP1A2 701 CYP2B6 547 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no	M1 8
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no	M1 8
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no	M1 8
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no	M1 8
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no	M1 8
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=172;https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf#page=8 Page: 172.0	no		no (co-administration study) Comment: No significant inhibition or induction of CYP3A4 enzyme using midazolam as a substrate was observed when IBSRELA 50 mg was administered twice a day for 13 days in healthy subjects. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=172;https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf#page=8 Page: 172.0
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=171;https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf#page=8 Page: 171.0	yes [IC50 0.4 uM]		no (co-administration study) Comment: No significant inhibition or induction of CYP3A4 enzyme using midazolam as a substrate was observed when IBSRELA 50 mg was administered twice a day for 13 days in healthy subjects. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=171;https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf#page=8 Page: 171.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf#page=8 Page: 8.0	minor	M1 13	yes (co-administration study) Comment: Following co-administration of a single dose of IBSRELA 50 mg with repeated doses of itraconazole 200 mg, a CYP3A4 inhibitor, the mean AUC and Cmax of M1 was decreased 50% in healthy subjects Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf#page=8 Page: 8.0
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=149 Page: 149.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=149 Page: 149.0	weak
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=149 Page: 149.0	weak
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=149 Page: 149.0	weak
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=149 Page: 149.0	weak
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=149 Page: 149.0	weak
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=149 Page: 149.0	weak
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=149 Page: 149.0	weak
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	yes
CYP3A5 395	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=58 Page: 58.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 49	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=37 Page: 37.0
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211801Orig1s000MultidisciplineR.pdf#page=32 Page: 32.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00A0DO	https://www.aablocks.com/goods/Goods/detail?id=AA00A0DO
AbMole Bioscience	M7572	http://www.abmole.com/products/tenapanor.html
Adooq BioScience	A14011	https://www.adooq.com/tenapanor.html
Ambeed	A984988	https://www.ambeed.com/products/1234423-95-0.html
BioChemPartner	BCP24892	http://www.biochempartner.com/1234423-95-0-BCP24892
BioChemPartner	BCP28554	http://www.biochempartner.com/AZD1722-BCP28554
Chem Scene	CS-6273	http://www.chemscene.com/1234423-95-0.html
ChemShuttle	183259	http://www.chemshuttle.com/catalogsearch/result/?q=1234423-95-0&cat=
Chemspace	CSSB00161189517	https://chem-space.com/CSSB00161189517
DC Chemicals	DC10386	http://www.dcchemicals.com/product_show-Tenapanor.html
Excenen	EX-A2506	https://www.excenen.com/searchresultlist.php?id=1234423-95-0
Lab Network	LN01344719	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01344719
Lan Pharmatech	LAN-B70883	http://www.lanpharmatech.com/product-9?_keywords=LAN-B70883
MedChem Express	HY-15991	https://www.medchemexpress.com/Tenapanor.html
MolPort	MolPort-046-417-118	https://www.molport.com/shop/molecule-link/MolPort-046-417-118
Smolecule	S544902	http://www.smolecule.com/products/s544902
Synblock Inc	SB19099	http://www.synblock.com/product/1234423-95-0.html
THE BioTek	bt-284017	https://www.thebiotek.com/product/inhibitors/bt-284017
abcr GmbH	AB479209	http://www.abcr.de/shop/en/AB479209
eNovation Chemicals	D593166	https://www.enovationchem.com/ProductDetails.asp?ProductID=D593166

PubMed

Title	Date	PubMed
Tenapanor hydrochloride for the treatment of constipation-predominant irritable bowel syndrome.	2015	26065434
Current and emerging treatments for irritable bowel syndrome with constipation and chronic idiopathic constipation: focus on prosecretory agents.	2015 Jun	26016701
Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial.	2017 May	28244495

Patents

Sample Use Guides

In Vivo Use Guide

twice-daily oral tenapanor (3, 10, or 30 mg [the latter down-titrated, if needed]) for 8 weeks

Route of Administration: Oral

Name

Type

Language

TENAPANOR

Official Name

English

RDX-013 COMPONENT TENAPANOR

Common Name

English

TENAPANOR COMPONENT OF RDX013

Common Name

English

Tenapanor [WHO-DD]

Common Name

English

tenapanor [INN]

Common Name

English

TENAPANOR [MI]

Common Name

English

TENAPANOR [USAN]

Common Name

English

KHK7791

Code

English

N,N'-(10,17,-DIOXO-3,6,21,24-TETRAOXA-9,11,16,18-TETRAAZAHEXACOSANE-1,26-DIYL)BIS(((4S)-6,8-DICHLORO-2-METHYL-1,2,3,4-TETRAHYDROISOQUINOLIN-4-YL)BENZENESULFONAMIDE)

Common Name

English

AZD-1722

Code

English

KHK-7791

Code

English

TENAPANOR COMPONENT OF RDX-013

Common Name

English

12,15-DIOXA-2,7,9-TRIAZAHEPTADECANAMIDE, 17-(((3-((4S)-6,8-DICHLORO-1,2,3,4-TETRAHYDRO-2-METHYL-4-ISOQUINOLINYL)PHENYL)SULFONYL)AMINO)-N-(2-(2-(2-(((3-((4S)-6,8-DICHLORO-1,2,3,4-TETRAHYDRO-2-METHYL-4-ISOQUINOLINYL)PHENYL)SULFONYL)AMINO)ETHOXY)ETHOXY)ETHY

Systematic Name

English

RDX013 COMPONENT TENAPANOR

Common Name

English

AZD1722

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C78276