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Pafolacianine API Manufacturers & Suppliers

General Description:

Pafolacianine, identified by CAS number 1628423-76-6, is a notable compound with significant therapeutic applications. Pafolacianine, or OTL38, is a folate analogue conjugated with a fluorescent dye that absorbs light in the near-infrared (NIR) spectrum within a range of 760 nm to 785 nm, with a peak absorption of 776 nm. It emits fluorescence within a range of 790 nm to 815 nm with a peak emission of 796 nm. The longer wavelength allows for deeper penetration of the fluorescent light through tissues for better imaging and detection of tumours. Pafolacianine targets the folate receptor alpha (FRα) which is upregulated in numerous epithelial malignancies. On November 29, 2021, the FDA approved pafolacianine as an adjunct imaging agent for intraoperative identification of malignant lesions in adult patients with ovarian cancer. It is currently under investigation for use in FRα-positive pituitary adenoma, lung cancer, and renal-cell carcinoma, which is thought to be the second-highest folate receptor-expressing cancer.

Indications:

This drug is primarily indicated for: Pafolacianine is an optical imaging agent indicated in adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Pafolacianine undergoes metabolic processing primarily in: The metabolism of pafolacianine is unknown; however, pafolacianine is not metabolized by cytochrome P450 (CYP) enzymes. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Pafolacianine are crucial for its therapeutic efficacy: The mean C_max of pafolacianine was 59.1 ± 5.94 ng/mL and AUC_inf was 63.6 ± 12.6 ng x hr/mL. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Pafolacianine is an important consideration for its dosing schedule: The elimination half-life of pafolacianine is 0.44 ± 0.23 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Pafolacianine exhibits a strong affinity for binding with plasma proteins: Plasma protein binding of pafolacianine is 93.7%. No notable partitioning into red blood cells was observed. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Pafolacianine from the body primarily occurs through: Following a single intravenous infusion of radiolabeled pafolacianine sodium, approximately 35% of the dose was recovered in urine (19.1%) and in feces (15.8%) after approximately 3-5 weeks. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Pafolacianine is distributed throughout the body with a volume of distribution of: The mean volume of distribution (V_z) is 17.1 ± 5.99 L, indicating distribution into tissues. During intraoperative molecular imaging for surgically resectable pulmonary adenocarcinoma, pafolacianine accumulated in nearly 70% of squamous cell carcinomas. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Pafolacianine is a critical factor in determining its safe and effective dosage: The mean plasma clearance is 28.6 ± 4.97 L/hr. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Pafolacianine exerts its therapeutic effects through: Tumor to background ratios changed with different mass doses studied. High tumor to background ratio was observed with 0.025 mg/kg dose. Pafolacianine exposure-response relationships and the time course of pharmacodynamic responses are unknown. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Pafolacianine functions by: Pafolacianine is consists of folic acid linked by its γ-carboxyl and a short spacer to an indocyanine green-related near-infrared dye called SO456. It is used for intraoperative fluorescence for tumour identification and surgical resection. It targets the folate receptor alpha (FRα), which is often overexpressed in various cancers including ovarian cancer. Pafolacianine binds to FRα-expressing cancer cells with an affinity of ~1 nM and is internalized via receptor-mediated endocytosis to be concentrated in FR-positive cancer tissues. Pafolacianine absorbs light and in the near-infrared (NIR) region within a range of 760 nm to 785 nm with a peak absorption of 776 nm and, upon excitation, emits fluorescence within a range of 790 nm to 815 nm with a peak emission of 796 nm. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Pafolacianine belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom, classified under the direct parent group Phenylalanine and derivatives. This compound is a part of the Organic compounds, falling under the Organic acids and derivatives superclass, and categorized within the Carboxylic acids and derivatives class, specifically within the Amino acids, peptides, and analogues subclass.

Categories:

Pafolacianine is categorized under the following therapeutic classes: Compounds used in a research, industrial, or household setting, Diagnostic Agents, Diagnostic Uses of Chemicals, Folic Acid Analogues, Heterocyclic Compounds, Fused-Ring, Laboratory Chemicals, Molecular Probes, OAT1/SLC22A6 Substrates, OATP1B1/SLCO1B1 Substrates, OATP1B3 substrates, Optical Imaging Agent, Pteridines, Pterins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.