Tasurgratinib is a small-molecule, orally active fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor developed under the code E7090. The pharmaceutical product approved in Japan is Tasurgratinib Succinate, marketed as Tasfygo. Tasurgratinib selectively inhibits FGFR1, FGFR2 and FGFR3 and is particularly relevant to tumors driven by FGFR2 gene fusions or rearrangements.
Tasurgratinib was first approved in Japan on 24 September 2024 for adults with unresectable biliary tract cancer harboring FGFR2 gene fusions or rearrangements that has progressed following cancer chemotherapy. The approved dosage is 140 mg of tasurgratinib orally once daily under fasting conditions, with dose adjustment according to the patient's condition.
The free-base active pharmaceutical ingredient has the molecular formula C32H37N5O6 and molecular weight approximately 587.7 g/mol. FDA's Global Substance Registration System identifies tasurgratinib under UNII TN7CUD1NGA, while PubChem lists E7090 as a synonym.
The approved Japanese pharmaceutical form is tasurgratinib succinate, specifically a sesquisuccinate salt. The Japanese Accepted Names database gives the salt composition as (C32H37N5O6)2·(C4H6O4)3, with molecular weight 1529.60 for the represented salt unit and CAS 1879965-80-6.
Tasurgratinib belongs to the kinase inhibitor class and is structurally designed to interact with the ATP-binding and allosteric regions of FGFRs. PMDA's review reports strong inhibitory activity against FGFR1, FGFR2 and FGFR3, with kinase IC50 values of approximately 0.891, 0.557 and 1.76 nmol/L, respectively. Activity against FGFR4 was substantially weaker at 124 nmol/L.
The molecule contains a substituted indole-based core, pyridine functionality, benzamide linkage and hydroxyethyl-piperidine moiety. PubChem reports 8 hydrogen-bond acceptors, 3 hydrogen-bond donors and a calculated molecular weight of 587.7 g/mol.
Tasurgratinib acts as an FGFR tyrosine kinase inhibitor. It binds to FGFR proteins and inhibits kinase signaling associated with aberrant fibroblast growth factor signaling. FGFR2 gene fusions and rearrangements can drive tumor growth in biliary tract cancer, making selective FGFR inhibition an important targeted therapeutic strategy.
PMDA's pharmacology review demonstrated inhibition of FGFR1–FGFR4 and additional activity against selected kinases including RET and VEGFR2. The strongest activity among the principal FGFRs was observed against FGFR2.
Tasurgratinib succinate is an oncology API associated with targeted treatment of FGFR2 fusion-positive unresectable biliary tract cancer. The Japanese approval was supported by clinical data in patients whose disease had progressed after previous chemotherapy.
Clinical development has also evaluated tasurgratinib in advanced solid tumors, including cholangiocarcinoma and gastric cancer with relevant FGFR alterations.
PMDA reports that the tasurgratinib drug substance is a white powder and that its characterization included description, solubility, acid dissociation constants, partition coefficient, pH, melting point, thermal analysis, hygroscopicity and crystalline polymorphism. Structural characterization included elemental analysis, UV-Vis, IR, NMR, mass spectrometry and single-crystal X-ray diffraction.
The drug-substance control strategy includes identification by IR, related substances by HPLC, residual solvents and residual amines, water content, particle size, microbial limits, and assay of both tasurgratinib and succinic acid. PMDA's public review does not disclose all numerical release limits because portions of the submitted specifications are redacted.
Tasurgratinib drug substance is manufactured through a controlled synthetic process with critical quality attributes and critical process parameters established through pharmaceutical development and risk assessment. The manufacturing control strategy covers chemical identity, active ingredient and succinic acid content, related substances, residual solvents/residual amines, particle size and microbial quality.
A pharmaceutical-grade Tasurgratinib API program should therefore use validated analytical procedures and an appropriate specification covering assay, related substances, residual solvents, water, particle-size requirements where applicable and microbiological quality.
Tasurgratinib free base has the molecular formula C32H37N5O6 and molecular weight 587.7 g/mol. The drug substance is described by PMDA as a white powder. Its reported pKa values are approximately 4.1 and 8.8, with a log P value of approximately 4.0.
The active pharmaceutical substance is also reported to be photolabile, making appropriate protection from light an important consideration during handling and storage.
Tasurgratinib API should be packed in suitable pharmaceutical-grade, well-closed containers that protect the material from environmental exposure, particularly light and moisture, according to the validated manufacturer's stability and packaging study.
PMDA reports that photostability testing identified the drug substance as photolabile. Consequently, light-protective packaging and controlled storage conditions should be established according to the applicable API specification and stability data.
Commercial pharmaceutical-grade Tasurgratinib API documentation may include:
A reliable Tasurgratinib API manufacturing program should emphasize identity, assay, impurity control, residual-solvent management, water content, particle-size control and microbiological quality using validated analytical procedures. Tasurgratinib succinate requires particular attention to the correct salt form and stoichiometry because the approved pharmaceutical substance is a sesquisuccinate, rather than the free-base tasurgratinib substance.
For pharmaceutical development and commercial requirements, Tasurgratinib API should be supplied with appropriate quality documentation and specifications aligned with the intended regulatory market and customer requirements.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |