Abaloparatide API Manufacturers

General Description:

Abaloparatide, identified by CAS number 247062-33-5, is a notable compound with significant therapeutic applications. Abaloparatide is an analog of PTHrP (parathyroid hormone-related protein). It was approved in April 28, 2017 by the FDA (as Tymlos) for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Abaloparatide is a synthetic peptide that is related to hPTHrP and has demonstrated in preclinical testing the potential to widen the anabolic window for bone therapeutics, stimulating bone formation with a limited effect on bone resorption and mineral mobilization. This could enable improved convenience over currently available anabolic therapies, resulting in greater compliance and, ultimately, greater benefit to patients. In October 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended abaloparatide be granted marketing authorization in Europe for the treatment of osteoporosis in postmenopausal women at increased risk of fracture. In December 2022, the FDA indication for abaloparatide was expanded to include male patients in addition to postmenopausal women.

Indications:

This drug is primarily indicated for: Abaloparatide is indicated for the treatment of osteoporosis in both men and postmenopausal women at high risk of fracture. It is also indicated in patients for whom other osteoporosis treatments are ineffective or intolerable. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Abaloparatide undergoes metabolic processing primarily in: Abaloparatide is metabolized into smaller peptide fragments via non-specific proteolytic degradation. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Abaloparatide are crucial for its therapeutic efficacy: The time it takes to reach peak concentration following subcutaneous administration of 80 mcg abaloparatide ranges from 0.25 to 0.52 hr, with the median time of 0.51hr. The bioavailability in healthy women is 36% following administration. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Abaloparatide is an important consideration for its dosing schedule: The mean (SD) half-life if 1.7 (0.7) hrs. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Abaloparatide exhibits a strong affinity for binding with plasma proteins: In vitro plasma protein binding is approximately 70%. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Abaloparatide from the body primarily occurs through: Metabolized products are mainly eliminated via renal excretion. Patients with severe renal impairment should be monitored with increased risk of adverse effects however there are no recommended dosage adjustments in patients with mild, moderate or severe renal impairment. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Abaloparatide is distributed throughout the body with a volume of distribution of: Vd is approximately 50L. This metric indicates how extensively the drug permeates into body tissues.

Pharmacodynamics:

Abaloparatide exerts its therapeutic effects through: Abaloparatide (BA058), a proprietary analog of human parathyroid hormone-related protein (hPTHrP), is currently undergoing clinical trials by the company for the treatment of osteoporosis in postmenopausal women. PTHrP is a critical peptide for promoting new bone formation, with a distinct role from parathyroid hormone, or PTH, which primarily regulates calcium homeostasis and bone resorption. Clinical studies show increased bone mineral density (BMD) and levels of bone formation markers in a dose-response relationship. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Abaloparatide functions by: In target cells, abaloparatide acts as an agonist on PTH type 1 receptor (PTH1R) and activates both G protein–mediated cAMP signaling and β-arrestin-mediated ERK-1/2 signaling pathways with similar potency. Abaloparatide binds to RG conformation of PTH1R with greater selectivity that results in more transient cell signalling responses. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Abaloparatide belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Abaloparatide is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Analogs/Derivatives, Biological Factors, Bone Density Conservation Agents, Calcium Homeostasis, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Intercellular Signaling Peptides and Proteins, Parathyroid Hormone-Related Protein, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Abaloparatide include:

• Water Solubility: Soluble
• Molecular Weight: 3961.0
• Molecular Formula: C174H300N56O49