Selpercatinib is a selective, orally active rearranged during transfection (RET) receptor tyrosine kinase inhibitor used in the treatment of cancers driven by RET alterations. It is also known by its development code LOXO-292. The compound has CAS No. 2152628-33-4, molecular formula C₂₉H₃₁N₇O₃, and molecular weight 525.61 g/mol. FDA identifies selpercatinib as a kinase inhibitor and confirms its chemical identity and molecular characteristics.
RET is a receptor tyrosine kinase that can become an oncogenic driver through gene fusions or activating mutations. These genetic alterations occur in several tumor types, including non-small-cell lung cancer (NSCLC), medullary thyroid cancer and other thyroid cancers. Selpercatinib was specifically developed to inhibit RET signaling while providing greater selectivity than earlier multikinase inhibitors.
Selpercatinib inhibits RET, including RET fusion proteins and mutant RET forms. It also has activity against VEGFR1 and VEGFR3, although its primary therapeutic development has focused on RET-driven cancers. FDA's original regulatory review describes selpercatinib as a RET receptor kinase inhibitor and reports its development for RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer and RET fusion-positive thyroid cancer.
The U.S. FDA initially approved selpercatinib in May 2020 for specific RET-driven cancers. Since then, its approved indications have expanded substantially. FDA granted traditional approval for RET-mutant medullary thyroid cancer in September 2024 and for RET fusion-positive thyroid cancer in June 2024. In July 2026, FDA granted traditional approval for locally advanced or metastatic RET fusion-positive solid tumors in adults and pediatric patients aged two years and older whose disease has progressed following prior systemic treatment or for whom no satisfactory alternative treatment exists.
Selpercatinib is a chemically defined small-molecule drug substance. FDA describes the material as a white to light-yellow powder that is slightly hygroscopic. Its aqueous solubility is pH dependent, ranging from freely soluble under acidic conditions to slightly soluble at neutral pH. The drug substance also exhibits polymorphism, making solid-state characterization and control important considerations for pharmaceutical manufacturing.
The chemical structure contains a pyrazolopyridine core, pyridine groups, a diazabicyclo[3.1.1]heptane moiety, a methoxy substituent and a nitrile functional group. FDA's chemical description gives the systematic name as 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile.
From an API manufacturing perspective, control of identity, assay, related substances, stereochemical integrity, residual solvents, elemental impurities, solid-state form and particle-size distribution is important. FDA's CMC review confirms that the drug substance specification includes impurity controls, elemental-impurity assessment under ICH Q3D and particle-size controls. However, several numerical acceptance criteria in the publicly available FDA review are redacted.
This means that numerical values should not be invented for a CMS product page. In particular, generic limits such as 98–102% assay, NMT 0.5% individual impurity or NMT 1.0% total impurities should not be presented as official Selpercatinib specifications unless supported by the applicable approved API specification or CoA.
Selpercatinib is supplied commercially as an oral capsule, with FDA-approved strengths including 40 mg and 80 mg in the original product review. These are finished pharmaceutical product strengths and should not be confused with the API specification.
The continued expansion of selpercatinib's regulatory indications demonstrates the importance of selective RET inhibition in precision oncology. For pharmaceutical API manufacturers, Selpercatinib represents a specialized oncology drug substance requiring strong analytical control, appropriate solid-state characterization and consistent batch-to-batch manufacturing performance.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |