Lenvatinib

Lenvatinib is an oral, multi-targeted tyrosine kinase inhibitor with IC50s of 4 and 5.2 nM for VEGFR2(KDR) and VEGFR3(Flt-4), respectively. Lenvatinib is less potent against VEGFR1/Flt-1 and shows approximately 10-fold selectivity for VEGFR2/3 over FGFR1, PDGFRα/β.
Lenvatinib is a member of the class of quinolines that is the carboxamide of 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxylic acid. A multi-kinase inhibitor and orphan drug used (as its mesylate salt) for the treatment of various types of thyroid cancer that do not respond to radioiodine. It has a role as a vascular endothelial growth factor receptor antagonist, an orphan drug, an antineoplastic agent, an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor and a fibroblast growth factor receptor antagonist. It is a member of quinolines, an aromatic ether, a monocarboxylic acid amide, an aromatic amide, a member of monochlorobenzenes, a member of cyclopropanes and a member of phenylureas. It is a conjugate base of a lenvatinib(1+).|Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. These receptor tyrosine kinases (RTKs) located in the cell membrane play a central role in the activation of signal transduction pathways involved in the normal regulation of cellular processes, such as cell proliferation, migration, apoptosis and differentiation, and in pathogenic angiogenesis, lymphogenesis, tumour growth and cancer progression. In particular, VEGF has been identified as a crucial regulator of both physiologic and pathologic angiogenesis and increased expression of VEGF is associated with a poor prognosis in many types of cancers. Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer. Most patients with thyroid cancer have a very good prognosis with treatment (98% 5 year survival rate) involving surgery and hormone therapy. However, for patients with RAI-refractory thyroid cancer, treatment options are limited and the prognosis is poor, leading to a push for the development of more targeted therapies such as lenvatinib.|Lenvatinib is a Kinase Inhibitor. The mechanism of action of lenvatinib is as a Receptor Tyrosine Kinase Inhibitor.|Lenvatinib is orally available multi-kinase inhibitor and antineoplastic agent that is used in treatment of advanced, metastatic medullary thyroid cancer and refractory renal cell carcinoma. Lenvatinib is associated with a modest rate of serum enzyme elevations during treatment and has been implicated to rare instances of clinically apparent, acute liver injury some of which have been fatal.|Lenvatinib is a synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. Lenvatinib blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis.