WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206958
CAS#: 1058156-90-3 (free base)
Description: Anlotinib, also known as AL3818 and Catequentinib, is a receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic and anti-angiogenic activities. Upon administration, anlotininib targets multiple RTKs, including vascular endothelial growth factor receptor type 2 (VEGFR2) and type 3 (VEGFR3). This agent may both inhibit angiogenesis and halt tumor cell growth.
MedKoo Cat#: 206958
Name: Anlotinib free base
CAS#: 1058156-90-3 (free base)
Chemical Formula: C23H22FN3O3
Exact Mass: 407.1645
Molecular Weight: 407.4454
Elemental Analysis: C, 67.80; H, 5.44; F, 4.66; N, 10.31; O, 11.78
Synonym: AL3818; AL-3818; AL 3818; Anlotinib; Anlotinib free base; Catequentinib
IUPAC/Chemical Name: 1-(((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropan-1-amine
InChi Key: KSMZEXLVHXZPEF-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H22FN3O3/c1-13-9-15-16(27-13)3-4-19(22(15)24)30-18-5-8-26-17-11-21(20(28-2)10-14(17)18)29-12-23(25)6-7-23/h3-5,8-11,27H,6-7,12,25H2,1-2H3
SMILES Code: NC1(COC2=C(OC)C=C3C(OC4=C(F)C5=C(NC(C)=C5)C=C4)=CC=NC3=C2)CC1
Appearance: 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
Shelf Life: >2 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:||Anlotinib (AL3818) is a highly potent and selective VEGFR2 inhibitor with IC50 less than 1 nM.|
|In vitro activity:||To investigate the anti-angiogenic activity of anlotinib, the effect of anlotinib on the migration of HUVEC in Transwell assays was examined. As shown in Figure 4A, anlotinib inhibited the migration of HUVEC to the lower side of the filter in the Transwell chamber in response to VEGF stimulation. This effect was concentration dependent, with an IC50 value of 0.1 nmol/L. At a concentration of 100 nmol/L, sunitinib also significantly inhibited the migration of HUVEC. It has been reported that VEGF cannot induce tube formation of HUVEC when cultured on Matrigel, so 20% FBS was selected as a stimulating factor to evaluate the effect of anlotinib on the tube formation of HUVEC. As shown in Figure 4B, anlotinib inhibited the ability of HUVEC to form tubes in a concentration‐dependent way. Following treatment with 100 nmol/L anlotinib, few enclosed tubes were detected. Reference: Cancer Sci. 2018 Apr;109(4):1207-1219. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29446853/|
|In vivo activity:||The in vivo antitumor potential of anlotinib was evaluated in the human colon cancer SW620 xenograft model. Once-daily oral dose of anlotinib caused dose-dependent inhibition of tumor growth (Figure 5A,C), inhibiting tumor growth by 83% compared with controls at a dose of 3 mg/kg. By comparison, the dose of sunitinib required to achieve comparable efficacy was 50 mg/kg in this model. Moreover, anlotinib had little effect on bodyweight in mice during the course of the experiment in all groups (Figure 5B). We further assessed tumor angiogenesis by measuring microvessel density in extracted tumors using an immunohistochemical analysis for CD31, an endothelial cell marker. Anlotinib induced a significant decrease in CD31‐positive microvessels, yielding inhibition rates of 48.9%, 76.3% and 91.2% at doses of 0.75, 1.5 and 3 mg/kg, respectively (Figure 5D). By comparison, sunitinib at a dose of 50 mg/kg inhibited microvessel density by 63.6%. Reference: Cancer Sci. 2018 Apr;109(4):1207-1219. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29446853/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 407.4454 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.
|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|
|In vitro protocol:||1. Xie C, Wan X, Quan H, Zheng M, Fu L, Li Y, Lou L. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor. Cancer Sci. 2018 Apr;109(4):1207-1219. doi: 10.1111/cas.13536. Epub 2018 Mar 25. PMID: 29446853; PMCID: PMC5891194.|
|In vivo protocol:||1. Xie C, Wan X, Quan H, Zheng M, Fu L, Li Y, Lou L. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor. Cancer Sci. 2018 Apr;109(4):1207-1219. doi: 10.1111/cas.13536. Epub 2018 Mar 25. PMID: 29446853; PMCID: PMC5891194.|
1: Zhong CC, Chen F, Yang JL, Jia WW, Li L, Cheng C, Du FF, Zhang SP, Xie CY, Zhang NT, Olaleye OE, Wang FQ, Xu F, Lou LG, Chen DY, Niu W, Li C. Pharmacokinetics and disposition of anlotinib, an oral tyrosine kinase inhibitor, in experimental animal species. Acta Pharmacol Sin. 2018 Apr 5. doi: 10.1038/aps.2017.199. [Epub ahead of print] PubMed PMID: 29620050.
2: Lin B, Song X, Yang D, Bai D, Yao Y, Lu N. Anlotinib inhibits angiogenesis via suppressing the activation of VEGFR2, PDGFRβ and FGFR1. Gene. 2018 May 15;654:77-86. doi: 10.1016/j.gene.2018.02.026. Epub 2018 Feb 14. PubMed PMID: 29454091.
3: Xie C, Wan X, Quan H, Zheng M, Fu L, Li Y, Lou L. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor. Cancer Sci. 2018 Apr;109(4):1207-1219. doi: 10.1111/cas.13536. Epub 2018 Mar 25. PubMed PMID: 29446853.
4: Sun W, Wang Z, Chen R, Huang C, Sun R, Hu X, Li W, Chen R. Influences of Anlotinib on Cytochrome P450 Enzymes in Rats Using a Cocktail Method. Biomed Res Int. 2017;2017:3619723. doi: 10.1155/2017/3619723. Epub 2017 Dec 26. PubMed PMID: 29441353; PubMed Central PMCID: PMC5758843.
5: Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13. PubMed PMID: 29438373; PubMed Central PMCID: PMC5846072.
6: Taurin S, Yang CH, Reyes M, Cho S, Coombs DM, Jarboe EA, Werner TL, Peterson CM, Janát-Amsbury MM. Endometrial Cancers Harboring Mutated Fibroblast Growth Factor Receptor 2 Protein Are Successfully Treated With a New Small Tyrosine Kinase Inhibitor in an Orthotopic Mouse Model. Int J Gynecol Cancer. 2018 Jan;28(1):152-160. doi: 10.1097/IGC.0000000000001129. PubMed PMID: 28953502; PubMed Central PMCID: PMC5735020.
7: Zhao J, Zhao H, Chi Y. The Safety and Efficacy of the S1/Temozolomide Regimen in Patients with Metastatic Neuroendocrine Tumors. Neuroendocrinology. 2017 Aug 17. doi: 10.1159/000480402. [Epub ahead of print] PubMed PMID: 28817826.
8: Sun Y, Niu W, Du F, Du C, Li S, Wang J, Li L, Wang F, Hao Y, Li C, Chi Y. Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors. J Hematol Oncol. 2016 Oct 4;9(1):105. PubMed PMID: 27716285; PubMed Central PMCID: PMC5051080.