Linzagolix API Manufacturers

General Description:

Linzagolix, identified by CAS number 935283-04-8, is a notable compound with significant therapeutic applications. Linzagolix is a non-peptide, selective antagonist of the gonadotropin-releasing hormone (GnRH) receptor. It has been studied for the treatment of estrogen-dependent conditions such as uterine fibroids and endometriosis. It is similar to other GnRH receptor antagonists like , , and . Uterine fibroids occur in >70% of women of reproductive age, and when symptomatic are associated with heavy menstrual bleeding, anemia, abdominal pain and pressure, bloating, increased urinary frequency, and reproductive dysfunction. As these fibroids are essentially estrogen-dependent phenomena, hormone therapies which suppress estrogen activity - including GnRH receptor antagonists like linzagolix - are thought to be beneficial by preventing intramyometrial growths in the endometrial glands. Linzagolix was approved for use in the European Union in June 2022 for the management of symptoms caused by uterine fibroids.

Indications:

This drug is primarily indicated for: Linzagolix is indicated for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Linzagolix undergoes metabolic processing primarily in: Up to seven metabolites of linzagolix have been quantified in patient plasma, urine, and feces, although plasma metabolites represent less than 10% of the total linzagolix-related exposure. Two primary demethylated metabolites - KP017 and KP046 - have been identified, with CYP2C9 primarily responsible for the formation of KP017 and CYP2C8, CYP2C9, and CYP3A4 are primarily responsible for the formation of KP046. Unchanged parent drug is the predominant circulating component in human plasma and in the urine, and one of the major components in the feces. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Linzagolix are crucial for its therapeutic efficacy: Linzagolix is quickly absorbed following oral administration, with C_max occurring approximately 2 hours following administration. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Linzagolix is an important consideration for its dosing schedule: The half-life of linzagolix following multiple doses is approximately 15 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Linzagolix exhibits a strong affinity for binding with plasma proteins: Linzagolix is highly protein-bound (>99%) in plasma, primarily to albumin. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Linzagolix from the body primarily occurs through: Linzagolix is primarily excreted in the urine, with approximately one-third eliminated via the feces. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Linzagolix is distributed throughout the body with a volume of distribution of: After seven days of oral administration of linzagolix 100mg or 200mg, the volume of distribution was 11.067 L and 11.178 L, respectively. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Linzagolix is a critical factor in determining its safe and effective dosage: The geometric mean apparent clearance following multiple oral doses of linzagolix 100mg or 200mg was 0.522 L/h and 0.499 L/h, respectively. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Linzagolix exerts its therapeutic effects through: The administration of linzagolix results in a dose-dependent suppression of luteinizing hormone and follicle-stimulating hormone, and a subsequent decrease in circulating estradiol concentrations. The median serum estradiol levels across all studied patients was in the range of 20 to 60 pg/mL, and progesterone levels were maintained ≤3.1 ng/mL in 83% of women receiving the 200mg dose of linzagolix and 68% of women receiving the 100mg dose. Linzagolix should be avoided in patients with severe hepatic impairment (Child-Pugh C) and in patients with moderate, severe, or end-stage renal disease (eGFR ≤59 mL/min). Some patients experienced a reduction in bone mineral density, varying from 3 to 8% - patients with an increased risk of fracture or osteoporosis should be monitored closely and should receive regular bone density scans to assess any on-going loss. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Linzagolix functions by: Linzagolix is a selective antagonist of the gonadotropin-releasing hormone (GnRH) receptor. It binds competitively to GnRH receptors in the pituitary gland, thereby inhibiting endogenous signaling and, in turn, the hypothalamic-pituitary-gonadal axis. More specifically, this inhibition of GnRH signaling results in the suppression of both luteinizing hormone and follicle-stimulating hormone signaling, the latter of which is responsible for stimulating the production of estrogen in the ovaries. Linzagolix, therefore, indirectly suppresses estrogen production and signaling, making it useful in the management of estrogen-dependent conditions like uterine fibroids. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Linzagolix is categorized under the following therapeutic classes: Anti-Gonadotropin-Releasing Hormones, BCRP/ABCG2 Substrates, Cytochrome P-450 CYP2C8 Inhibitors, Cytochrome P-450 CYP2C8 Inhibitors (strength unknown), Cytochrome P-450 CYP2C8 Substrates, Cytochrome P-450 CYP2C9 Substrates, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Substrates, Gonadotropin Releasing Hormone Receptor Antagonists, Hypothalamic Hormones, OAT1/SLC22A6 inhibitors, OAT3/SLC22A8 Inhibitors, OAT3/SLC22A8 Substrates, OATP1B1/SLCO1B1 Inhibitors, OATP1B1/SLCO1B1 Substrates, OATP1B3 inhibitors, OATP1B3 substrates, Pituitary and Hypothalamic Hormones and Analogues, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Linzagolix include:

• Water Solubility: Slightly soluble