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Tenapanor API Manufacturers & Suppliers

General Description:

Tenapanor, identified by CAS number 1234423-95-0, is a notable compound with significant therapeutic applications. Tenapanor is a novel, small molecule medication approved in September 2019 for the treatment of constipation-predominant irritable bowel-syndrome (IBS-C). It was first designed and synthesized in 2012. As an inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3) transporter, it is the first and currently only medication within its class and therefore exists as a novel alternative in the treatment of IBS-C.

Indications:

This drug is primarily indicated for: Tenapanor is indicated for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) in adults. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Tenapanor undergoes metabolic processing primarily in: The majority of tenapanor's metabolism to its primary metabolite, M1, is catalyzed via CYP3A4/5. Exposure of tenapanor to hepatic CYP enzymes is likely limited due to its minimal systemic absorption, so its metabolism may be due to intestinal CYP enzyme activity. The M1 metabolite of tenapanor is a P-glycoprotein substrate and, in contrast to its parent drug, can be detected in plasma, reaching a C_max of approximately 15 ng/mL at steady state. It is not considered active against NHE3. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Tenapanor are crucial for its therapeutic efficacy: Tenapanor undergoes very minimal systemic absorption following oral administration. During clinical trials, plasma concentrations were below the limit of quantitation (i.e. less than 0.5 ng/mL) in the majority of samples from healthy subjects - for this reason, typical pharmacokinetic values related to absorption such as AUC and C_max were unable to be ascertained. The effects of tenapanor are greatest when administered 5 to 10 minutes before meals. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Tenapanor is an important consideration for its dosing schedule: Tenapanor's FDA label states that its half-life could not be determined during clinical trials due to its minimal systemic absorption resulting in plasma concentrations below the limit of quantitation (i.e. less than 0.5 ng/mL). This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Tenapanor exhibits a strong affinity for binding with plasma proteins: Both tenapanor and its principle metabolite, M1, are highly plasma protein bound at approximately 99% and 97%, respectively. The specific proteins to which tenapanor and its metabolite binds have yet to be elucidated. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Tenapanor from the body primarily occurs through: Following administration of a radio labeled dose of tenapanor, 70% of the radioactivity was excreted in the feces within 120 hours of administration and 79% within 240 hours. Approximately 65% of the total dose is excreted as unchanged parent drug within 144 hours of administration. Only 9% of the administered dose was found in the urine, existing primarily as metabolites. Tenapanor's M1 metabolite is excreted unchanged in the urine and accounts for approximately 1.5% of the total dose within 144 hours of administration. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Pharmacodynamics:

Tenapanor exerts its therapeutic effects through: Through the inhibition of dietary sodium absorption tenapanor causes an increase in water secretion into the intestines, thereby decreasing transit time and softening stool consistency. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tenapanor functions by: Tenapanor is a locally-acting small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), an antiporter expressed on the apical surface of enterocytes in the small intestine and colon which is involved in sodium-fluid homeostasis. By inhibiting this antiporter tenapanor causes retention of sodium within the lumen of the intestine - this results in an osmotic gradient that draws water into the lumen and softens stool consistency. There is some evidence that tenapanor can inhibit the uptake of dietary phosphorus in the gastrointestinal tract, though the exact mechanism of this activity has yet to be elucidated. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Tenapanor belongs to the class of organic compounds known as 4-phenyltetrahydroisoquinolines. These are compounds containing a phenyl group attached to the C4-atom of a tetrahydroisoquinoline moiety, classified under the direct parent group 4-phenyltetrahydroisoquinolines. This compound is a part of the Organic compounds, falling under the Organoheterocyclic compounds superclass, and categorized within the Tetrahydroisoquinolines class, specifically within the 4-phenyltetrahydroisoquinolines subclass.

Categories:

Tenapanor is categorized under the following therapeutic classes: Alimentary Tract and Metabolism, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 CYP3A5 Substrates, Cytochrome P-450 Substrates, Drugs for Constipation, Heterocyclic Compounds, Fused-Ring, Organic Anion Transporting Polypeptide 2B1 Inhibitors, Sodium/Hydrogen Exchanger 3 (NHE3) Inhibitors, Sulfur Compounds. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Tenapanor include:

• Water Solubility: Practically insoluble