tenapanor 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
5349 1234423-95-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tenapanor
  • tenapanor hydrochloride
  • RDX5791
  • AZD1722
  • AZD-1722
  • AZD1722-hydrochloride
  • KHK-7791
  • RDX-5791
  • ibsrela
IBSRELA (tenapanor) tablets contain tenapanor hydrochloride as an active ingredient. Tenapanor hydrochloride is a sodium/hydrogen exchanger 3 (NHE3) inhibitor for oral use, an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium. In vitro and animal studies indicate its major metabolite, M1, is not active against NHE3. By inhibiting NHE3 on the apical surface of the enterocytes, tenapanor reduces absorption of sodium from the small intestine and colon, resulting in an increase in water secretion into the intestinal lumen, which accelerates intestinal transit time and results in a softer stool consistency.
  • Molecular weight: 1145.04
  • Formula: C50H66Cl4N8O10S2
  • CLOGP: 7.53
  • LIPINSKI: 4
  • HAC: 18
  • HDO: 6
  • TPSA: 218
  • ALOGS: -5.59
  • ROTB: 27
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
S (Water solubility) 0.00 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 0 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.011 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 77.804 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.187 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 17.140 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.330 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.260 % High 1
herg hERG pIC50 5.198 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 21.135 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 235.505 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.290 % High 1
kinase-safety-class ACVR2B,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,GRK2,ITK,MAPK7,MAPKAPK2,MET,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PIK3CG,PRKDC,SIK2,SIK3,TEK 26
kinase-selectivity-class AXL,BRAF,GRK2,PDK1,SIK2,TEK 6
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 30.761 High 1
mh-clint Mouse hepatocyte intrinsic clearance 83.560 High 1
mppb Mouse plasma protein binding (% unbound) 0.260 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 32.137 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.670 % High 1
rh-clint Rat hepatocyte intrinsic clearance 43.652 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 0.500 % High 1
rppb Rat plasma protein binding (% unbound) 0.250 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.752 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 12, 2019 FDA ARDELYX INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 697.15 44.68 313 1089 938877 89688168
Hospitalisation 114.22 44.68 50 1352 128050 90498995
Inappropriate schedule of product administration 91.42 44.68 45 1357 149888 90477157
Death 76.45 44.68 60 1342 456491 90170554
Therapy interrupted 49.21 44.68 21 1381 50087 90576958

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 999.80 59.56 416 1115 460433 42159371
Hospitalisation 203.59 59.56 82 1449 74248 42545556
Death 147.89 59.56 126 1405 471059 42148745
Inappropriate schedule of product administration 107.35 59.56 57 1474 95845 42523959

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 773.08 42.67 345 1189 1139160 109448605
Death 165.28 42.67 108 1426 698761 109889004
Hospitalisation 98.23 42.67 45 1489 142448 110445317
Inappropriate schedule of product administration 64.00 42.67 38 1496 203599 110384166
Therapy interrupted 48.12 42.67 20 1514 49802 110537963
Shunt occlusion 44.36 42.67 9 1525 1728 110586037

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A06AX08 ALIMENTARY TRACT AND METABOLISM
DRUGS FOR CONSTIPATION
DRUGS FOR CONSTIPATION
Other drugs for constipation
FDA MoA N0000190109 Organic Anion Transporting Polypeptide 2B1 Inhibitors
FDA EPC N0000194056 Sodium-Hydrogen Exchanger 3 Inhibitor
FDA MoA N0000194057 Sodium-Hydrogen Exchanger 3 Inhibitors
CHEBI has role CHEBI:50503 laxative
CHEBI has role CHEBI:53784 antispasmodic drug

Related Drugs by ATC class:

A06AX Other drugs for constipation 7 drugs
elobixibatglycerollinaclotidelubiprostoneplecanatideprucalopridetegaserod

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Irritable bowel syndrome characterized by constipation indication 440630006
Chronic kidney disease indication 709044004
Gastrointestinal obstruction contraindication 126765001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.53 acidic
pKa2 10.13 acidic
pKa3 13.34 acidic
pKa4 13.74 acidic
pKa5 7.19 Basic
pKa6 6.59 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 50MG BASE IBSRELA ARDELYX INC N211801 Sept. 12, 2019 RX TABLET ORAL 9408840 Dec. 30, 2029 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION BY ADMINISTERING TENAPANOR
EQ 50MG BASE IBSRELA ARDELYX INC N211801 Sept. 12, 2019 RX TABLET ORAL 9006281 May 2, 2030 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION BY ADMINISTERING TENAPANOR
EQ 10MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 DISCN TABLET ORAL 10272079 April 10, 2034 REDUCTION OF SERUM PHOSPHORUS IN ADULTS
EQ 10MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 DISCN TABLET ORAL 10272079 April 10, 2034 TREATMENT OF HYPERPHOSPHATEMIA
EQ 10MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 DISCN TABLET ORAL 10940146 April 10, 2034 REDUCTION OF SERUM PHOSPHORUS IN ADULTS
EQ 10MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 DISCN TABLET ORAL 10940146 April 10, 2034 TREATMENT OF HYPERPHOSPHATEMIA
EQ 20MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL 10272079 April 10, 2034 REDUCTION OF SERUM PHOSPHORUS IN ADULTS
EQ 20MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL 10272079 April 10, 2034 TREATMENT OF HYPERPHOSPHATEMIA
EQ 20MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL 10940146 April 10, 2034 REDUCTION OF SERUM PHOSPHORUS IN ADULTS
EQ 20MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL 10940146 April 10, 2034 TREATMENT OF HYPERPHOSPHATEMIA
EQ 30MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL 10272079 April 10, 2034 REDUCTION OF SERUM PHOSPHORUS IN ADULTS
EQ 30MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL 10272079 April 10, 2034 TREATMENT OF HYPERPHOSPHATEMIA
EQ 30MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL 10940146 April 10, 2034 REDUCTION OF SERUM PHOSPHORUS IN ADULTS
EQ 30MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL 10940146 April 10, 2034 TREATMENT OF HYPERPHOSPHATEMIA

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 10MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 DISCN TABLET ORAL Oct. 17, 2026 NEW PRODUCT
EQ 20MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL Oct. 17, 2026 NEW PRODUCT
EQ 30MG BASE XPHOZAH ARDELYX INC N213931 Oct. 17, 2023 RX TABLET ORAL Oct. 17, 2026 NEW PRODUCT

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Sodium/hydrogen exchanger 3 Transporter INHIBITOR IC50 9.06 SCIENTIFIC LITERATURE DRUG LABEL
Sodium/hydrogen exchanger 3 Transporter IC50 8.20 CHEMBL

External reference:

IDSource
WYD79216A6 UNII
1234365-97-9 SECONDARY_CAS_RN
4041253 VANDF
C4043480 UMLSCUI
CHEBI:755312 CHEBI
CHEMBL3304485 ChEMBL_ID
71587953 PUBCHEM_CID
DB11761 DRUGBANK_ID
CHEMBL3301627 ChEMBL_ID
D11652 KEGG_DRUG
9652 INN_ID
C000599417 MESH_SUPPLEMENTAL_RECORD_UI
8449 IUPHAR_LIGAND_ID
789705000 SNOMEDCT_US
792892003 SNOMEDCT_US
323087 MMSL
37400 MMSL
d09370 MMSL
018117 NDDF
018118 NDDF
2199673 RXNORM

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
IBSRELA HUMAN PRESCRIPTION DRUG LABEL 1 73154-050 TABLET 53.20 mg ORAL NDA 29 sections
XPHOZAH 10 mg HUMAN PRESCRIPTION DRUG LABEL 1 73154-110 TABLET, FILM COATED 10 mg ORAL NDA 28 sections
XPHOZAH 20 mg HUMAN PRESCRIPTION DRUG LABEL 1 73154-120 TABLET, FILM COATED 20 mg ORAL NDA 28 sections
XPHOZAH 30 mg HUMAN PRESCRIPTION DRUG LABEL 1 73154-130 TABLET, FILM COATED 30 mg ORAL NDA 28 sections