Lenvatinib mesylate
[CAS 857890-39-2]

Identification

• Classification: Biochemical >> Inhibitor >> Protein tyrosine kinase
• Name: Lenvatinib mesylate
• Synonyms: 4-[3-Chloro-4-[[(cyclopropylamino)carbonyl]amino]phenoxy]-7-methoxy-6-quinolinecarboxamide monomethanesulfonate; E 7080 mesylate
• Molecular Formula: C₂₁H₁₉ClN₄O₄.CH₄O₃S
• Molecular Weight: 522.96
• CAS Registry Number: 857890-39-2
• EC Number: 812-398-0
• SMILES: COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl.CS(=O)(=O)O

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H302-H360-H361-H361d-H362-H372-H373
• Safety Statements: P203-P260-P263-P264-P270-P280-P301+P317-P318-P319-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	1B	H360
Reproductive toxicity	Lact.	-	H362

Discovery and Applications

Lenvatinib mesylate is the mesylate salt form of lenvatinib, a small-molecule multi-targeted tyrosine kinase inhibitor used in oncology. It is approved for the treatment of several cancers, including differentiated thyroid cancer, renal cell carcinoma (in combination regimens), hepatocellular carcinoma, and endometrial carcinoma in specific settings.

Lenvatinib is designed to inhibit multiple receptor tyrosine kinases that are involved in tumor angiogenesis and cancer cell proliferation. Its primary targets include vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), fibroblast growth factor receptors (FGFR1–4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT. By simultaneously inhibiting these signaling pathways, lenvatinib disrupts both tumor blood vessel formation and tumor cell growth signaling.

At the molecular level, lenvatinib binds competitively to the ATP-binding pocket of these receptor tyrosine kinases. This prevents autophosphorylation of the receptors and blocks downstream signaling cascades such as the MAPK and PI3K/AKT pathways, which are essential for cell proliferation, survival, and angiogenesis. The broad kinase inhibition profile of lenvatinib contributes to its anti-tumor activity across multiple cancer types.

Structurally, lenvatinib is a synthetic heteroaromatic compound containing a substituted quinoline-like core linked to various aromatic and aliphatic substituents. These structural features enable high-affinity binding to the kinase domains of its target receptors. The molecule was developed through structure–activity relationship studies aimed at optimizing multi-kinase inhibition while maintaining oral bioavailability.

The mesylate (methanesulfonate) salt form is used to improve the physicochemical properties of the drug, particularly its stability and manufacturability. Salt formation is a common pharmaceutical strategy to enhance dissolution rate, solid-state stability, and consistency in oral dosage forms.

Lenvatinib mesylate is administered orally and is absorbed systemically, where it distributes to tissues and reaches tumor sites. It undergoes hepatic metabolism, primarily via enzymatic pathways including cytochrome P450-mediated oxidation. The pharmacokinetics of lenvatinib support once-daily dosing in most clinical regimens.

Clinically, lenvatinib is used either as monotherapy or in combination with other anticancer agents. In differentiated thyroid cancer, it is used for radioactive iodine-refractory disease. In hepatocellular carcinoma and renal cell carcinoma, it is often combined with immune checkpoint inhibitors or other targeted therapies depending on treatment protocols. In endometrial carcinoma, it is used in combination with pembrolizumab in certain settings.

Common adverse effects associated with lenvatinib include hypertension, diarrhea, fatigue, decreased appetite, weight loss, and proteinuria. These effects are consistent with its anti-angiogenic activity, particularly inhibition of VEGF signaling, which plays a role in normal vascular function.

From a pharmacological perspective, lenvatinib is considered a multi-targeted kinase inhibitor with strong anti-angiogenic and anti-proliferative effects. Its ability to inhibit both VEGFR and FGFR pathways distinguishes it from some earlier anti-angiogenic agents that primarily target VEGF signaling alone.

Overall, lenvatinib mesylate is an orally active multi-kinase inhibitor that blocks several receptor tyrosine kinases involved in tumor growth and angiogenesis. Its mesylate salt form improves pharmaceutical properties, while its broad kinase inhibition profile underlies its clinical utility in multiple types of advanced cancers.

References

2012. Unique metabolic pathway of [(14)C]lenvatinib after oral administration to male cynomolgus monkey. Drug metabolism and disposition: the biological fate of chemicals.
DOI: 10.1124/dmd.111.043281