Lenvatinib metabolite

[1]. Lenvatinib: A Promising Molecular Targeted Agent for Multiple Cancers. Cancer Control. 2018 Jan-Dec;25(1):1073274818789361.

[2]. Lenvatinib versus Bay 43-9006 in first-line treatment of patients with unresectable hepatocellularcarcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173.

Lenvatinib is a small-molecule tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor α (PDGFRα), stem cell factor receptor (KIT), and transfection rearrangement receptor (RET). These receptors are crucial for tumor angiogenesis, and lenvatinib inhibits tumor angiogenesis by suppressing the function of these receptors. Phase I clinical trials of lenvatinib were conducted simultaneously in Japan, Europe, and the United States, and tumor shrinkage effects were observed in thyroid cancer, endometrial cancer, melanoma, renal cell carcinoma, sarcoma, and colon cancer. Lenvatinib is a promising drug that has shown efficacy in treating a variety of solid tumors. Adverse reactions to lenvatinib treatment may include hypertension, proteinuria, diarrhea, and delayed wound healing. Managing these adverse events is also crucial for the use of lenvatinib. In this short review article, we summarize the current status, toxicities, and future prospects of lenvatinib in the treatment of thyroid cancer, hepatocellular carcinoma, renal cell carcinoma, and lung cancer. [1]

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Background: Lenvatinib (an inhibitor of VEGF receptors 1–3, FGF receptors 1–4, PDGF receptor α, RET, and KIT) showed activity against hepatocellular carcinoma in a phase II clinical trial. We aimed to compare lenvatinib with sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma. Methods: This was an open-label, phase III, multicenter, non-inferiority trial that enrolled patients with unresectable hepatocellular carcinoma who had not received prior treatment for advanced disease at 154 research centers in 20 countries across Asia Pacific, Europe, and North America. Patients were randomized 1:1 using an interactive voice response system, with grouping factors including: geographic location; gross portal vein invasion, extrahepatic metastasis, or both; Eastern Cooperative Oncology Group (ECOG) performance status score; and weight. Patients received either oral lenvatinib (12 mg daily for those weighing ≥60 kg, 8 mg daily for those weighing <60 kg) or sorafenib (400 mg twice daily) for 28 days as one course of treatment. The primary endpoint was overall survival, defined as the time from randomization to death from any cause. Efficacy analysis followed the intention-to-treat principle, and safety analysis included only patients who received treatment. The non-inferiority margin was set at 1.08. This trial was registered at ClinicalTrials.gov under registration number NCT01761266. Results: Between March 1, 2013, and July 30, 2015, a total of 1492 patients were enrolled. 954 eligible patients were randomized to either the lenvatinib group (n=478) or the sorafenib group (n=476). The median survival in the lenvatinib group was 13.6 months (95% CI 12.1–14.9), which was non-inferior to the sorafenib group (12.3 months, 10.4–13.9; hazard ratio 0.92, 95% CI 0.79–1.06), meeting the non-inferiority criteria. The most common adverse events of any grade in the lenvatinib group were hypertension (201 cases [42%]), diarrhea (184 cases [39%]), decreased appetite (162 cases [34%]), and weight loss (147 cases [31%]); the most common adverse events of any grade in the sorafenib group were hand-foot syndrome (249 cases [52%]), diarrhea (220 cases [46%]), hypertension (144 cases [30%]), and decreased appetite (127 cases [27%]). Conclusion: In treatment-naïve patients with advanced hepatocellular carcinoma, lenvatinib was non-inferior to sorafenib in terms of overall survival. The safety and tolerability of lenvatinib were consistent with previous observations. [2]

C20H18CL2N4O4

449.29

448.07051

O-Demethyl Lenvatinib;417717-04-5

168007119

Light yellow to yellow solid powder

KMZOGLZCTDVLLW-UHFFFAOYSA-N

InChI=1S/C20H17ClN4O4.ClH/c21-14-7-11(3-4-15(14)25-20(28)24-10-1-2-10)29-18-5-6-23-16-9-17(26)13(19(22)27)8-12(16)18;/h3-10,26H,1-2H2,(H2,22,27)(H2,24,25,28);1H

4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-hydroxyquinoline-6-carboxamide;hydrochloride

O-Demethyl Lenvatinib (hydrochloride); O-Demethyl Lenvatinib hydrochloride;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO :~50 mg/mL (~111.29 mM)

Solubility in Formulation 1: ≥ 1.8 mg/mL (4.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 18.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)