Lenvatinib mesylate
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MedKoo CAT#: 201080

CAS#: 857890-39-2 (mesylate)

Description: Lenvatinib, also known as E7080, 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. E7080 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.


Chemical Structure

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Lenvatinib mesylate
CAS# 857890-39-2 (mesylate)

Theoretical Analysis

MedKoo Cat#: 201080
Name: Lenvatinib mesylate
CAS#: 857890-39-2 (mesylate)
Chemical Formula: C22H23ClN4O7S
Exact Mass:
Molecular Weight: 522.96
Elemental Analysis: C, 50.53; H, 4.43; Cl, 6.78; N, 10.71; O, 21.42; S, 6.13

Price and Availability

Size Price Availability Quantity
100.0mg USD 90.0 Ready to ship
200.0mg USD 150.0 Ready to ship
500.0mg USD 300.0 Ready to ship
1.0g USD 550.0 Ready to ship
2.0g USD 950.0 Ready to ship
5.0g USD 2050.0 Ready to ship
10.0g USD 3750.0 Ready to ship
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Related CAS #: 857890-39-2 (mesylate)   417716-92-8 (free base)    

Synonym: E7080; E-7080; E 7080; ER-203492-00; Lenvatinib; Lenvatinib mesylate; trade name Lenvima.

IUPAC/Chemical Name: 4-(3-chloro-4-(3-cyclopropylureido)phenoxy)-7-methoxyquinoline-6-carboxamide mesylate

InChi Key: HWLFIUUAYLEFCT-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H19ClN4O4.CH4O3S/c1-29-19-10-17-13(9-14(19)20(23)27)18(6-7-24-17)30-12-4-5-16(15(22)8-12)26-21(28)25-11-2-3-11;1-5(2,3)4/h4-11H,2-3H2,1H3,(H2,23,27)(H2,25,26,28);1H3,(H,2,3,4)

SMILES Code: O=C(C1=C(OC)C=C2N=CC=C(OC3=CC=C(NC(NC4CC4)=O)C(Cl)=C3)C2=C1)N.OS(=O)(C)=O

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Lenvatinib mesylate (E7080 mesylate) is a tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, PDGFR, KIT, and RET.
In vitro activity: The antiproliferative activity of lenvatinib against nine HCC cell lines was examined in vitro. Lenvatinib showed selective and potent antiproliferative activity against the HCC cell lines Hep3B2.1‐7, HuH‐7, and JHH‐7, with IC50 values of 0.23, 0.42, and 0.64 μmol/L, respectively (Fig. 1A and B). Immunoblotting analysis showed that FGF19, FGFR4, and β‐Klotho were highly expressed in these three cell lines, indicating that the FGF19–FGFR4 axis was activated (Fig. 1C), consistent with previous reports. Lenvatinib also showed moderate inhibitory effects on the proliferation of SNU‐398, Li‐7, and HuH‐1 cells, with IC50 values of 1.56, 1.65, and 2.59 μmol/L, respectively (Fig. 1A and B). Although FGF19 protein was not expressed, some members of the FGFR family were detected in these cells (Fig. 1C). Because these cell lines are modestly sensitive to pan‐FGFR inhibitors such as BGJ398, lenvatinib might inhibit proliferation of the cells by targeting an activated FGF signaling pathway. Lenvatinib did not show clear antiproliferative activity against SK‐HEP‐1, SNU‐449, or PLC/PRF/5 cells (IC50 >5 μmol/L; Fig. 1A and B), which were also insensitive to pan‐FGFR inhibitors. Reference: Cancer Med. 2018 Jun;7(6):2641-2653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010799/
In vivo activity: The in vivo antitumor activity of lenvatinib against HCC (human hepatocellular carcinoma) xenografts with activated FGF signaling pathways in the Hep3B2.1‐7 and SNU‐398 models was evaluated. In vivo growth of xenograft tumors was significantly inhibited by lenvatinib at doses of 3–30 mg/kg in the Hep3B2.1‐7 model and 10, 30 mg/kg in the SNU‐398 model (Fig. 3A). BWL (body weight loss) of the treatment group was similar to that of the corresponding vehicle control group, although cachexia‐induced BWL was observed in each control group (Fig. S5). To examine whether lenvatinib inhibited FGF signaling pathways within the Hep3B2.1‐7 and SNU‐398 xenograft tumors, tumor samples were collected 2 h after a single lenvatinib treatment, and phosphorylation levels of FRS2 and another downstream molecule of FGFR, Erk1/2, were evaluated. Lenvatinib at 10 and 30 mg/kg inhibited phosphorylation of FRS2 and Erk1/2 in the Hep3B2.1‐7 model (Fig. 3C); lenvatinib at 3–30 mg/kg inhibited FRS2 phosphorylation in the SNU‐398 model (Fig. 3E); and lenvatinib at 30 mg/kg inhibited Erk1/2 phosphorylation in the SNU‐398 model (Fig. 3E). These results suggest that targeting FGFR of HCC cells underlies the antitumor activity of lenvatinib in preclinical HCC models with activated FGF signaling pathways. Reference: Cancer Med. 2018 Jun;7(6):2641-2653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010799/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 5.78 11.05
DMSO:PBS (pH 7.2) (1:5) 0.16 0.31

Preparing Stock Solutions

The following data is based on the product molecular weight 522.96 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ogasawara S, Mihara Y, Kondo R, Kusano H, Akiba J, Yano H. Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. Anticancer Res. 2019 Nov;39(11):5973-5982. doi: 10.21873/anticanres.13802. PMID: 31704822. 2. Matsuki M, Hoshi T, Yamamoto Y, Ikemori-Kawada M, Minoshima Y, Funahashi Y, Matsui J. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 2018 Jun;7(6):2641-2653. doi: 10.1002/cam4.1517. Epub 2018 May 7. PMID: 29733511; PMCID: PMC6010799.
In vitro protocol: 1. Ogasawara S, Mihara Y, Kondo R, Kusano H, Akiba J, Yano H. Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. Anticancer Res. 2019 Nov;39(11):5973-5982. doi: 10.21873/anticanres.13802. PMID: 31704822. 2. Matsuki M, Hoshi T, Yamamoto Y, Ikemori-Kawada M, Minoshima Y, Funahashi Y, Matsui J. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 2018 Jun;7(6):2641-2653. doi: 10.1002/cam4.1517. Epub 2018 May 7. PMID: 29733511; PMCID: PMC6010799.
In vivo protocol: 1. Ogasawara S, Mihara Y, Kondo R, Kusano H, Akiba J, Yano H. Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. Anticancer Res. 2019 Nov;39(11):5973-5982. doi: 10.21873/anticanres.13802. PMID: 31704822. 2. Matsuki M, Hoshi T, Yamamoto Y, Ikemori-Kawada M, Minoshima Y, Funahashi Y, Matsui J. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 2018 Jun;7(6):2641-2653. doi: 10.1002/cam4.1517. Epub 2018 May 7. PMID: 29733511; PMCID: PMC6010799.

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1: Sato N, Beppu T, Kinoshita K, Yuki H, Suyama K, Yuruki H, Motohara T, Chiyonaga S, Akahoshi S. Partial Splenic Embolization for Lenvatinib Therapy-associated Thrombocytopenia Among Patients With Hepatocellular Carcinoma. Anticancer Res. 2019 Dec;39(12):6895-6901. doi: 10.21873/anticanres.13909. PubMed PMID: 31810959.

2: Rinninella E, Cintoni M, Raoul P, Mele MC, De Gaetano AM, Marini MG, Mora V, Gasbarrini A. Minimal impact of lenvatinib (Lenvima®) on muscle mass in advanced hepatocellular carcinoma and implications for treatment duration. Two cases from the REFLECT study. Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):10132-10138. doi: 10.26355/eurrev_201911_19583. PubMed PMID: 31799685.

3: Feng F, Li X, Li R, Li B. The multiple-kinase inhibitor lenvatinib inhibits the proliferation of acute myeloid leukemia cells. Animal Model Exp Med. 2019 Sep 3;2(3):178-184. doi: 10.1002/ame2.12076. eCollection 2019 Sep. PubMed PMID: 31773093; PubMed Central PMCID: PMC6762047.

4: Kudo M. A New Treatment Option for Intermediate-Stage Hepatocellular Carcinoma with High Tumor Burden: Initial Lenvatinib Therapy with Subsequent Selective TACE. Liver Cancer. 2019 Oct;8(5):299-311. doi: 10.1159/000502905. Epub 2019 Sep 18. PubMed PMID: 31768341; PubMed Central PMCID: PMC6872999.

5: Hatanaka T, Kakizaki S, Nagashima T, Namikawa M, Tojima H, Shimada Y, Takizawa D, Naganuma A, Arai H, Sato K, Harimoto N, Shirabe K, Uraoka T. Analyses of objective response rate, progression-free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study. Hepatol Res. 2019 Nov 23. doi: 10.1111/hepr.13460. [Epub ahead of print] PubMed PMID: 31760660.

6: Aydemirli MD, Kapiteijn E, Ferrier KRM, Ottevanger N, Links TP, van der Horst-Schrivers ANA, Broekman KE, Groenwold RHH, Zwaveling J. Effectiveness and toxicity of lenvatinib in refractory thyroid cancer: Dutch real-life data. Eur J Endocrinol. 2019 Nov 1. pii: EJE-19-0763.R1. doi: 10.1530/EJE-19-0763. [Epub ahead of print] PubMed PMID: 31751307.

7: Kim JJ, McFarlane T, Tully S, Wong WWL. Lenvatinib Versus Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma: A Cost-Utility Analysis. Oncologist. 2019 Nov 20. pii: theoncologist.2019-0501. doi: 10.1634/theoncologist.2019-0501. [Epub ahead of print] PubMed PMID: 31748341.

8: Honda S, Saitho Y, Sawada K, Hasebe T, Nakajima S, Okumura T. Repeated Perforation of the Gallbladder in a Patient with Hepatocellular Carcinoma Receiving Lenvatinib. Intern Med. 2019 Nov 18. doi: 10.2169/internalmedicine.3806-19. [Epub ahead of print] PubMed PMID: 31735795.

9: Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T, Fujishiro M. Favorable radiologic antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma. Hepatol Res. 2019 Nov 12. doi: 10.1111/hepr.13452. [Epub ahead of print] PubMed PMID: 31721363.

10: Yamashita T, Kudo M, Ikeda K, Izumi N, Tateishi R, Ikeda M, Aikata H, Kawaguchi Y, Wada Y, Numata K, Inaba Y, Kuromatsu R, Kobayashi M, Okusaka T, Tamai T, Kitamura C, Saito K, Haruna K, Okita K, Kumada H. REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset. J Gastroenterol. 2019 Nov 12. doi: 10.1007/s00535-019-01642-1. [Epub ahead of print] PubMed PMID: 31720835.

11: Sasaki R, Fukushima M, Haraguchi M, Miuma S, Miyaaki H, Hidaka M, Eguchi S, Matsuo S, Tajima K, Matsuzaki T, Hashimoto S, Ooba K, Kugiyama Y, Yatsuhashi H, Motoyoshi Y, Shigeno M, Kinoshita N, Nakao K. Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings. Cancers (Basel). 2019 Nov 10;11(11). pii: E1769. doi: 10.3390/cancers11111769. PubMed PMID: 31717674.

12: Hida T, Velcheti V, Reckamp KL, Nokihara H, Sachdev P, Kubota T, Nakada T, Dutcus CE, Ren M, Tamura T. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer. 2019 Dec;138:124-130. doi: 10.1016/j.lungcan.2019.09.011. Epub 2019 Sep 16. PubMed PMID: 31710864.

13: Ogasawara S, Mihara Y, Kondo R, Kusano H, Akiba J, Yano H. Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. Anticancer Res. 2019 Nov;39(11):5973-5982. doi: 10.21873/anticanres.13802. PubMed PMID: 31704822.

14: Liu Z, Li X, He X, Xu Y, Wang X. Complete response to the combination of Lenvatinib and Pembrolizumab in an advanced hepatocellular carcinoma patient: a case report. BMC Cancer. 2019 Nov 8;19(1):1062. doi: 10.1186/s12885-019-6287-8. PubMed PMID: 31703571; PubMed Central PMCID: PMC6839182.

15: Chen WX, Li GX, Hu ZN, Zhu P, Zhang BX, Ding ZY. Significant response to anti-PD-1 based immunotherapy plus lenvatinib for recurrent intrahepatic cholangiocarcinoma with bone metastasis: A case report and literature review. Medicine (Baltimore). 2019 Nov;98(45):e17832. doi: 10.1097/MD.0000000000017832. Review. PubMed PMID: 31702638; PubMed Central PMCID: PMC6855517.

16: Hou FJ, Guo LX, Zheng KY, Song JN, Wang Q, Zheng YG. Chelidonine enhances the antitumor effect of lenvatinib on hepatocellular carcinoma cells. Onco Targets Ther. 2019 Aug 19;12:6685-6697. doi: 10.2147/OTT.S215103. eCollection 2019. PubMed PMID: 31695406; PubMed Central PMCID: PMC6707434.

17: Chen X, Zhang Y, Zhang N, Ge Y, Jia W. Lenvatinib combined nivolumab injection followed by extended right hepatectomy is a feasible treatment for patients with massive hepatocellular carcinoma: a case report. Onco Targets Ther. 2019 Sep 9;12:7355-7359. doi: 10.2147/OTT.S217123. eCollection 2019. PubMed PMID: 31686845; PubMed Central PMCID: PMC6752163.

18: Tada T, Kumada T, Hiraoka A, Michitaka K, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T, Takaguchi K, Kariyama K, Itobayashi E, Tajiri K, Shimada N, Shibata H, Ochi H, Toyoda H, Nouso K, Tsutsui A, Nagano T, Itokawa N, Hayama K, Imai M, Joko K, Koizumi Y, Hiasa Y. Safety and efficacy of lenvatinib in elderly patients with unresectable hepatocellular carcinoma: A multicenter analysis with propensity score matching. Hepatol Res. 2019 Oct 29. doi: 10.1111/hepr.13427. [Epub ahead of print] PubMed PMID: 31660700.

19: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK547897/ PubMed PMID: 31643233.

20: Molinaro E, Viola D, Viola N, Falcetta P, Orsolini F, Torregrossa L, Vagli P, Ribechini A, Materazzi G, Vitti P, Elisei R. Lenvatinib Administered via Nasogastric Tube in Poorly Differentiated Thyroid Cancer. Case Rep Endocrinol. 2019 Sep 18;2019:6831237. doi: 10.1155/2019/6831237. eCollection 2019. PubMed PMID: 31641541; PubMed Central PMCID: PMC6766666.



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