Larotrectinib is a selective tropomyosin receptor kinase (TRK) inhibitor and active pharmaceutical ingredient used in the treatment of cancers with NTRK gene fusions. It is a precision oncology medicine designed to target the underlying molecular driver of tumors rather than a specific anatomical cancer type.
Larotrectinib selectively inhibits TRKA, TRKB and TRKC, which are encoded by the NTRK1, NTRK2 and NTRK3 genes. NTRK gene fusions can result in constitutively active TRK signaling, contributing to uncontrolled cell proliferation and tumor growth. By inhibiting TRK signaling, Larotrectinib can interfere with pathways involved in cancer-cell survival and proliferation.
Larotrectinib is a synthetic small-molecule kinase inhibitor. It has the molecular formula C21H22F2N6O2 and a molecular weight of approximately 428.44 g/mol. Its CAS Number is 1223403-58-4.
Larotrectinib is generally supplied as a pharmaceutical-grade active ingredient for formulation and pharmaceutical manufacturing applications.
Larotrectinib is a highly selective inhibitor of the tropomyosin receptor kinase (TRK) family, including TRKA, TRKB and TRKC.
NTRK gene fusions can produce abnormal TRK proteins with continuous kinase activity. Larotrectinib binds to the ATP-binding region of TRK proteins and inhibits their kinase activity. This suppresses downstream signaling pathways involved in cell proliferation, differentiation and survival.
Larotrectinib is used for the treatment of solid tumors that have an NTRK gene fusion, when the tumor is metastatic or surgical resection is likely to result in severe morbidity and there are no satisfactory alternative treatments or the cancer has progressed following treatment.
The therapy is an example of a tumor-agnostic targeted treatment, because eligibility is determined by the presence of an NTRK gene fusion rather than solely by the tumor's anatomical site.
Larotrectinib API can be evaluated using validated analytical procedures for identification, assay, related substances, water content, residual solvents, elemental impurities and other applicable quality attributes.
HPLC and suitable spectroscopic and analytical techniques may be used for identity, assay and purity testing. Acceptance criteria should be based on the applicable approved manufacturer's drug-substance specification, Certificate of Analysis and relevant regulatory requirements.
Larotrectinib should be stored in a tightly closed pharmaceutical-grade container under controlled storage conditions. The API should be protected from excessive heat, moisture, direct light and contamination. Specific storage requirements should follow the applicable manufacturer's approved specification.
Larotrectinib API may be supplied for qualified pharmaceutical manufacturing, formulation development, research and analytical applications. Product specifications, Certificate of Analysis, packaging details and regulatory documentation should be confirmed according to the intended application.
Larotrectinib API is available for pharmaceutical development and manufacturing requirements subject to applicable quality and regulatory requirements. Customers can request product specifications, analytical documentation, Certificate of Analysis, packaging information and commercial details for their specific requirements.
| Parameter | Specification |
|---|---|
| Appearance | White to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 10 ppm |
| pH (1% Solution) | 2.0 – 4.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |