In vitro: Tenapanor exhibits human and rat NHE3 with IC50 values of 5 and 10 nM, respectively. Human intestinal transporters NHE1, NHE2, TGR5, ASBT, and Pit-1 and the sodium-dependent phosphate transporter NaPiIIb are not inhibited by tenapanor at concentrations up to 10 to 30 μM.
In vivo: Tenapanor plays a prominent role in sodium handling in the gastrointestinal tract and kidney. It acts exclusively in the gastrointestinal tract to inhibit sodium uptake when administered orally to rats. Average plasma Cmax values of tenapanor in rats and humans are less than 1 ng/mL with negligible area under the curve at doses of up to 30mg/kg in rats, 10mg/kg in dogs, and 900 mg in humans. Dose-dependent reductions in urinary sodium and increases in fecal sodium and luminal fluid mass are observed upon administering single doses of tenapanor to rats. Chronic administration of tenapanor to rats fed with standard chow (0.49% NaCl) causes a sustained reduction of urinary sodium and increase in fecal sodium.
| Cell Experiment | |
|---|---|
| Cell lines | |
| Preparation method | |
| Concentrations | |
| Incubation time | |
| Animal Experiment | |
|---|---|
| Animal models | Rats |
| Formulation | water |
| Dosages | 10 ml/kg |
| Administration | oral |
| Molecular Weight | 1145.05 |
| Formula | C50H66Cl4N₈O10S2 |
| CAS Number | 1234423-95-0 |
| Solubility (25°C) | 10 mM in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Na+/H+ Exchanger (NHE) Products |
|---|
| NHE3-IN-1
NHE3-IN-1 is an inhibitor of sodium/proton exchanger 3 (NHE-3). |
| NHE3-IN-2
NHE3-IN-2 is a Na+/H+ exchanger 3 (NHE3) inhibitor. |
| Eniporide
Eniporide (EMD 96785) is a Na(+)/H(+) exchange (NHE) inhibitor. |
| Zoniporide hydrochloride hydrate
Zoniporide (CP-597396) hydrochloride hydrate is a potent and selective inhibitor of sodium-hydrogen exchanger type 1 (NHE-1). Zoniporide hydrochloride hydrate inhibits human NHE-1 (IC50=14 nM), and has >150-fold selectivity versus other NHE isoforms. Zoniporide hydrochloride hydrate potently inhibits ex vivo NHE-1-dependent swelling of human platelets (IC50=59 nM). |
| Zoniporide hydrochloride
Zoniporide (CP-597396) hydrochloride is a potent and selective inhibitor of sodium-hydrogen exchanger type 1 (NHE-1). Zoniporide hydrochloride inhibits human NHE-1 (IC50=14 nM), and has >150-fold selectivity versus other NHE isoforms. Zoniporide hydrochloride potently inhibits ex vivo NHE-1-dependent swelling of human platelets (IC50=59 nM). |
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