WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206058
CAS#: 1360460-82-7 (HCl)
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#: 206058
Name: Anlotinib HCl
CAS#: 1360460-82-7 (HCl)
Chemical Formula: C23H24Cl2FN3O3
Molecular Weight: 480.3614
Elemental Analysis: C, 57.51; H, 5.04; Cl, 14.76; F, 3.96; N, 8.75; O, 9.99
Synonym: AL3818; AL-3818; AL 3818; Anlotinib; Anlotinib HCl; Anlotinib dihydrochloride. Catequentinib,
IUPAC/Chemical Name: 1-(((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropan-1-amine dihydrochloride
InChi Key: UUAKQNIPIXQZFN-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H22FN3O3.2ClH/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;2*1H
SMILES Code: NC1(COC2=C(OC)C=C3C(OC4=C(F)C5=C(NC(C)=C5)C=C4)=CC=NC3=C2)CC1.[H]Cl.[H]Cl
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, 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:||Anlotinib HCl is a receptor tyrosine kinase (RTK) inhibitor that primarily inhibits VEGFR2/3, FGFR1-4, PDGFRα/β, c-Kit, and Ret.|
|In vitro activity:||Transforming growth factor-β1 (TGF-β1) is considered to be the most critical fibrogenic factor involved in the development of IPF (idiopathic pulmonary fibrosis) and its function depends on the signal transduction and regulation of Smad and non-Smad. Smad3 is the main activation protein of TGF-β/Smad signalling pathway, regulating a series of gene expression, and promotes fibroblast differentiation and proliferation. The constructed CAGA-NIH3T3 cell line stably transfected with the TGF-β1/Smad3 signalling pathway reporter plasmid was used to detect the effect of anlotinib hydrochloride on TGF-β1/Smad3 signalling pathway. As shown in Figure 5a, luciferases assay showed that anlotinib inhibited the TGFβ1/Smad3 signalling pathway in a dose-dependent manner. According to the results of Luciferases assay, 1 μM was selected as the best effective concentration for subsequent experiments. Further, it was observed that anlotinib hydrochloride significantly inhibited TGF-β1-induced phosphorylation of Smad3 protein, as shown in Figure 5b. Reference: J Pharm Pharmacol. 2020 Jan;72(1):44-55. https://academic.oup.com/jpp/article/72/1/44/6122084|
|In vivo activity:||The effect of anlotinib on bleomycin-induced pulmonary fibrosis in mice was evaluated. The histological changes at 14 days are shown in Figure 2a. In the saline group, there was no obvious inflammatory reaction and fibrosis in the lung tissue of mice, and the lung tissue structure was normal. After bleomycin was injected, not only the airway wall was significantly thickened, but also the alveolar structure was disordered. Meanwhile, the lung tissue of mice showed obvious alveolar inflammation, and some alveoli appeared realistic changes and fibrosis. In addition, the mice with bleomycin injection showed higher Ashcroft score than in control group. After anlotinib intervention, the above lesions were alleviated, and the Ashcroft score was significantly reduced (Figure 2b). It was also observed that the content of hydroxyproline in the left lung of mice in bleomycin group was significantly higher than that in saline group, as shown in Figure 2c. In anlotinib-treated group, the hydroxyproline content decreased, indicating that anlotinib inhibited ECM (extracellular matrix) deposition. The effect of anlotinib on the forced vital capacity in bleomycin-induced pulmonary fibrosis mice was also evaluated. The results showed that anlotinib increased the lung capacity of mice (Figure 2d). Reference: J Pharm Pharmacol. 2020 Jan;72(1):44-55. https://academic.oup.com/jpp/article/72/1/44/6122084|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 480.3614 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|
|Formulation protocol:||1. Ruan H, Lv Z, Liu S, Zhang L, Huang K, Gao S, Gan W, Liu X, Zhang S, Helian K, Li X, Zhou H, Yang C. Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway. J Pharm Pharmacol. 2020 Jan;72(1):44-55. doi: 10.1111/jphp.13183. Epub 2019 Oct 28. PMID: 31659758.|
|In vitro protocol:||1. Ruan H, Lv Z, Liu S, Zhang L, Huang K, Gao S, Gan W, Liu X, Zhang S, Helian K, Li X, Zhou H, Yang C. Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway. J Pharm Pharmacol. 2020 Jan;72(1):44-55. doi: 10.1111/jphp.13183. Epub 2019 Oct 28. PMID: 31659758.|
|In vivo protocol:||1. Ruan H, Lv Z, Liu S, Zhang L, Huang K, Gao S, Gan W, Liu X, Zhang S, Helian K, Li X, Zhou H, Yang C. Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway. J Pharm Pharmacol. 2020 Jan;72(1):44-55. doi: 10.1111/jphp.13183. Epub 2019 Oct 28. PMID: 31659758.|
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.
1360460-82-7 (Anlotinib Dihydrochloride)