Tenapanor

Summary

Tenapanor (CHEMBL3304485) is an approved small molecule (ATC A06AX08) targeting SLC9A3; indicated across 3 conditions including constipation disorder and irritable bowel syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A06AX08
• Targets: 1 (SLC9A3)
• Indications: 3 conditions
• Clinical trials: 35
• Chemistry: 1145 Da · C50H66Cl4N8O10S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3304485
Name	Tenapanor
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	71587953
ATC	A06AX08
Molecular formula	C50H66Cl4N8O10S2
Molecular weight	1145
InChIKey	DNHPDWGIXIMXSA-CXNSMIOJSA-N

SMILES: CN1C[C@H](C2=C(C1)C(=CC(=C2)Cl)Cl)C3=CC(=CC=C3)S(=O)(=O)NCCOCCOCCNC(=O)NCCCCNC(=O)NCCOCCOCCNS(=O)(=O)C4=CC=CC(=C4)[C@@H]5CN(CC6=C5C=C(C=C6Cl)Cl)C

IUPAC name: 1-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethyl]-3-[4-[2-[2-[2-[[3-[(4S)-6,8-dichloro-2-methyl-3,4-dihydro-1H-isoquinolin-4-yl]phenyl]sulfonylamino]ethoxy]ethoxy]ethylcarbamoylamino]butyl]urea

Also known as: AZD-1722, KHK-7791, Khk7791, Tenapanor, Tenapanor component of rdx-013, Tenapanor component of rdx013, TENAPANOR, TENAPANOR FREE BASE, AZD1722, AZD 1722, RDX 5791, RDX5791

Parent form; salt/anhydrous children: CHEMBL3301627

Patent coverage: 72 distinct patent families (201 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 154 (77%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SLC9A3	Sodium/hydrogen exchanger 3	Inhibition	7	2.2%	P48764

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Sodium/hydrogen exchanger 3, Sodium/hydrogen exchanger 3.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 9 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC9A3	9.3	IC50	0.5	nM	CHEMBL_ACT_24860120
SLC9A3	8.3	IC50	5.01	nM	CHEMBL_ACT_16889761
SLC9A3	8.3	IC50	5.01	nM	CHEMBL_ACT_18714767
SLC9A3	8.3	IC50	5.01	nM	CHEMBL_ACT_27563468
SLC9A3	8.2	IC50	6.31	nM	CHEMBL_ACT_27563486
P26433	8.03	IC50	9.33	nM	CHEMBL_ACT_16889760
P26433	8.03	IC50	9.33	nM	CHEMBL_ACT_18714471
SLC9A3	8	IC50	10	nM	CHEMBL_ACT_27563483
P26433	7.8	IC50	15.85	nM	CHEMBL_ACT_24860163

Target pathways

Aggregated over 1 target gene(s): SLC9A3.

Top Reactome pathways

4 total, by targets touching each:

Pathway	Targets	Genes
Transport of small molecules	1	SLC9A3
R-HSA-425393	1	SLC9A3
SLC-mediated transmembrane transport	1	SLC9A3
Sodium/Proton exchangers	1	SLC9A3

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	1
regulation of intracellular pH	1
potassium ion transmembrane transport	1
sodium ion import across plasma membrane	1
monoatomic cation transport	1
sodium ion transport	1
regulation of pH	1
sodium ion transmembrane transport	1
transmembrane transport	1
proton transmembrane transport	1

Indications & clinical

Indications

3 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
constipation disorder	4	MONDO:0002203	HP:0002019
irritable bowel syndrome	3	MONDO:0005052	EFO:0000555
hyperphosphatemia	3	MONDO:0000328	MONDO:0000328

Clinical trials

Total trials: 35.

Phase distribution

Phase	Trials
PHASE3	12
PHASE2	9
PHASE1	8
PHASE4	4
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03988920	PHASE4	COMPLETED	A Long-Term Study of Tenapanor Alone or in Combination With Sevelamer in Patients With CKD on Dialysis and HP
NCT04549597	PHASE4	COMPLETED	Study to Evaluate the Use of Tenapanor as Core Therapy in the Treatment of Hyperphosphatemia
NCT05995899	PHASE4	COMPLETED	Effect of Tenapanor on the Metagenomics and Metabolomics of Patients With Irritable Bowel Syndrome With Constipation
NCT06481150	PHASE4	COMPLETED	A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.
NCT05643534	PHASE3	RECRUITING	Study to Assess Safety and Efficacy of Tenapanor for Treatment of IBS-C in Pediatric Patients 12 to Less Than 18 Years
NCT05905926	PHASE3	ENROLLING_BY_INVITATION	Safety Study of Tenapanor for the Treatment of Pediatric Patients (6 to Less Than 18 Years Old) With IBS-C
NCT06810167	PHASE3	RECRUITING	Assessing Tenapanor as a Treatment of CF-related Constipation.
NCT01923428	PHASE2/PHASE3	COMPLETED	The Efficacy of AZD1722 in Constipation Predominant Irritable Bowel Syndrome (IBS-C)
NCT02621892	PHASE3	COMPLETED	A 12-Week Study With a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Tenapanor for the Treatment of IBS-C
NCT02675998	PHASE3	COMPLETED	An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
NCT02686138	PHASE3	COMPLETED	A 26-Week Study to Evaluate the Efficacy and Safety of Tenapanor in IBS-C
NCT02727751	PHASE3	COMPLETED	A Long-Term Safety Study of Tenapanor for the Treatment of IBS-C
NCT03427125	PHASE3	COMPLETED	A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis
NCT03824587	PHASE2/PHASE3	COMPLETED	Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy
NCT04766385	PHASE3	COMPLETED	Clinical Study of KHK7791 in Hyperphosphatemia Patients on Peritoneal Dialysis
NCT04766398	PHASE3	COMPLETED	Phosphate Binder-combination Study of KHK7791 in Hyperphosphatemia Patients on Hemodialysis
NCT04767581	PHASE3	COMPLETED	Clinical Study of KHK7791 in Hyperphosphatemia Patients on Hemodialysis
NCT04771780	PHASE3	COMPLETED	Phosphate Binder Switch Study of KHK7791 in Hyperphosphatemia Patients on Hemodialysis
NCT06460038	PHASE2	RECRUITING	Tenapanor in Synucleinopathy-Related Constipation
NCT06553547	PHASE2	RECRUITING	4-Week, Multi-center Dose-Ranging Study for the IBS-C in Pts. 6 to <12 Yrs
NCT01340053	PHASE2	COMPLETED	A Study to Evaluate the Safety and Efficacy of RDX5791 for the Treatment of Constipation Predominant Irritable Bowel Syndrome (IBS-C)
NCT01764854	PHASE2	COMPLETED	Pharmacodynamic Study of AZD1722 in End-stage Renal Disease Patients on Hemodialysis
NCT01847092	PHASE2	COMPLETED	A Study in CKD Patients With Type 2 Diabetes Mellitus and Albuminuria
NCT02081534	PHASE2	COMPLETED	Dose Finding Study to Treat High Phosphate Levels in the Blood.
NCT03831607	PHASE2	COMPLETED	A Phosphate Binder Switch Study of KHK7791 in Hyperphosphatemia Patients on HD
NCT03864445	PHASE2	COMPLETED	Phosphate Binder-combination Study of KHK7791 in Hyperphosphatemia Patients
NCT03864458	PHASE2	COMPLETED	Dose-finding Study of KHK7791 in Hyperphosphatemia Patients
NCT02063386	PHASE1	COMPLETED	AZD1722 Open Label, Absorption Distribution Metabolism and Excretion Study
NCT02140268	PHASE1	COMPLETED	To Evaluate the Effect of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers
NCT02176252	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics and Pharmacodynamic of AZD1722 in Healthy Male and Female Japanese Subjects
NCT02249936	PHASE1	COMPLETED	A Phase 1 Study to Examine the Pharmacodynamics of Different AZD1722 Formulations
NCT02346890	PHASE1	COMPLETED	A Phase 1 Study to Examine the Effect of Renvela on the Pharmacodynamics of AZD1722
NCT02796131	PHASE1	COMPLETED	Safety, Tolerability, and Pharmacodynamics of RDX5791 in Healthy Volunteers
NCT02819687	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RDX5791 in Healthy Volunteers
NCT06203444	PHASE1	COMPLETED	An Open-label Study to Evaluate the Pharmacokinetics of Oral Tenapanor in Breast Milk of Lactating Females

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

1 molecules share ≥1 primary target. Top 1 by shared-target count:

Molecule	Source	Status	Shared targets
ENIPORIDE	ChEMBL	Phase 2	SLC9A3