WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206958
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.
Hodoodo Cat#: H206958
Name: Anlotinib free base
CAS#: 1058156-90-3 (free base)
Chemical Formula: C23H22FN3O3
Exact Mass: 407.16
Molecular Weight: 407.445
Elemental Analysis: C, 67.80; H, 5.44; F, 4.66; N, 10.31; O, 11.78
Related CAS #: 1058156-90-3 (free base) 1360460-82-7 (HCl)
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
More Info:
| 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 | |
|---|---|---|---|
| Solubility | |||
| DMSO | 48.0 | 99.93 | |
| Water | 96.0 | 199.85 |
The following data is based on the product molecular weight 407.45 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: | |
| 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: Shen G, Zheng F, Ren D, Du F, Dong Q, Wang Z, Zhao F, Ahmad R, Zhao J. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol. 2018 Sep 19;11(1):120. doi: 10.1186/s13045-018-0664-7. PMID: 30231931; PMCID: PMC6146601.
2: Gao Y, Liu P, Shi R. Anlotinib as a molecular targeted therapy for tumors. Oncol Lett. 2020 Aug;20(2):1001-1014. doi: 10.3892/ol.2020.11685. Epub 2020 May 28. PMID: 32724339; PMCID: PMC7377159.
3: Syed YY. Anlotinib: First Global Approval. Drugs. 2018 Jul;78(10):1057-1062. doi: 10.1007/s40265-018-0939-x. Erratum in: Drugs. 2018 Aug;78(12):1287. PMID: 29943374.
4: Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1569-1575. doi: 10.1001/jamaoncol.2018.3039. Erratum in: JAMA Oncol. 2018 Nov 1;4(11):1625. PMID: 30098152; PMCID: PMC6248083.
5: Li S. Anlotinib: A Novel Targeted Drug for Bone and Soft Tissue Sarcoma. Front Oncol. 2021 May 20;11:664853. doi: 10.3389/fonc.2021.664853. PMID: 34094958; PMCID: PMC8173120.
6: Lv B, Chen J, Liu XL. Anlotinib-Induced Hypertension: Current Concepts and Future Prospects. Curr Pharm Des. 2022;28(3):216-224. doi: 10.2174/1381612827666211006145141. PMID: 34620054.
7: Liang L, Hui K, Hu C, Wen Y, Yang S, Zhu P, Wang L, Xia Y, Qiao Y, Sun W, Fei J, Chen T, Zhao F, Yang B, Jiang X. Autophagy inhibition potentiates the anti- angiogenic property of multikinase inhibitor anlotinib through JAK2/STAT3/VEGFA signaling in non-small cell lung cancer cells. J Exp Clin Cancer Res. 2019 Feb 12;38(1):71. doi: 10.1186/s13046-019-1093-3. PMID: 30755242; PMCID: PMC6373028.
8: 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.
9: Xu Q, Wang J, Sun Y, Lin Y, Liu J, Zhuo Y, Huang Z, Huang S, Chen Y, Chen L, Ke M, Li L, Li Z, Pan J, Song Y, Liu R, Chen C. Efficacy and Safety of Sintilimab Plus Anlotinib for PD-L1-Positive Recurrent or Metastatic Cervical Cancer: A Multicenter, Single-Arm, Prospective Phase II Trial. J Clin Oncol. 2022 Jun 1;40(16):1795-1805. doi: 10.1200/JCO.21.02091. Epub 2022 Feb 22. PMID: 35192397; PMCID: PMC9148684.
10: Ruan X, Shi X, Dong Q, Yu Y, Hou X, Song X, Wei X, Chen L, Gao M. Antitumor effects of anlotinib in thyroid cancer. Endocr Relat Cancer. 2019 Jan 1;26(1):153-164. doi: 10.1530/ERC-17-0558. PMID: 30139768; PMCID: PMC6215907.
11: Su Y, Luo B, Lu Y, Wang D, Yan J, Zheng J, Xiao J, Wang Y, Xue Z, Yin J, Chen P, Li L, Zhao Q. Anlotinib Induces a T Cell-Inflamed Tumor Microenvironment by Facilitating Vessel Normalization and Enhances the Efficacy of PD-1 Checkpoint Blockade in Neuroblastoma. Clin Cancer Res. 2022 Feb 15;28(4):793-809. doi: 10.1158/1078-0432.CCR-21-2241. PMID: 34844980; PMCID: PMC9377760.
12: Chen W, Zhang J, Zhong W, Liu Y, Lu Y, Zeng Z, Huang H, Wan X, Meng X, Zou F, Cai S, Dong H. Anlotinib Inhibits PFKFB3-Driven Glycolysis in Myofibroblasts to Reverse Pulmonary Fibrosis. Front Pharmacol. 2021 Sep 16;12:744826. doi: 10.3389/fphar.2021.744826. PMID: 34603058; PMCID: PMC8481786.
13: Chu T, Zhong R, Zhong H, Zhang B, Zhang W, Shi C, Qian J, Zhang Y, Chang Q, Zhang X, Dong Y, Teng J, Gao Z, Qiang H, Nie W, Zhao Y, Han Y, Chen Y, Han B. Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC. J Thorac Oncol. 2021 Apr;16(4):643-652. doi: 10.1016/j.jtho.2020.11.026. Epub 2021 Jan 29. PMID: 33524601.
14: Li D, Chi Y, Chen X, Ge M, Zhang Y, Guo Z, Wang J, Chen J, Zhang J, Cheng Y, Li Z, Liu H, Qin J, Zhu J, Cheng R, Xu Z, Zheng X, Tang P, Gao M. Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial. Clin Cancer Res. 2021 Jul 1;27(13):3567-3575. doi: 10.1158/1078-0432.CCR-20-2950. Epub 2021 Apr 8. PMID: 33832949.
15: Jin Z, Lu Y, Wu X, Pan T, Yu Z, Hou J, Wu A, Li J, Yang Z, Li C, Yan M, Yan C, Zhu Z, Liu B, Qiu W, Su L. The cross-talk between tumor cells and activated fibroblasts mediated by lactate/BDNF/TrkB signaling promotes acquired resistance to anlotinib in human gastric cancer. Redox Biol. 2021 Oct;46:102076. doi: 10.1016/j.redox.2021.102076. Epub 2021 Jul 20. PMID: 34315112; PMCID: PMC8326414.
16: Song F, Hu B, Cheng JW, Sun YF, Zhou KQ, Wang PX, Guo W, Zhou J, Fan J, Chen Z, Yang XR. Anlotinib suppresses tumor progression via blocking the VEGFR2/PI3K/AKT cascade in intrahepatic cholangiocarcinoma. Cell Death Dis. 2020 Jul 24;11(7):573. doi: 10.1038/s41419-020-02749-7. PMID: 32709873; PMCID: PMC7381674.
17: 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. Erratum in: Gene. 2020 Jan 10;723:144119. PMID: 29454091.
18: Zhang X, Zeng L, Li Y, Xu Q, Yang H, Lizaso A, Mao X, Jin R, Zeng Y, Li Q, Wang J, Li Y, Zhang Y, Yang N. Anlotinib combined with PD-1 blockade for the treatment of lung cancer: a real-world retrospective study in China. Cancer Immunol Immunother. 2021 Sep;70(9):2517-2528. doi: 10.1007/s00262-021-02869-9. Epub 2021 Feb 10. PMID: 33566148.
19: Chi Y, Shu Y, Ba Y, Bai Y, Qin B, Wang X, Xiong J, Xu N, Zhang H, Zhou J, Xu J, Cheng Y, Feng J, Hu C, Chen Y, Chen Z, Wang J, Dang C, Wang J, Wan Y, Tang Y, Wang D, Liu J, Wu M, Deng Y, Li X, Li Y, Dong J, Jiang D, Li G, Wu Q, Li J, Qi Y, Sun Y, Cai J. Anlotinib Monotherapy for Refractory Metastatic Colorectal Cancer: A Double-Blinded, Placebo-Controlled, Randomized Phase III Trial (ALTER0703). Oncologist. 2021 Oct;26(10):e1693-e1703. doi: 10.1002/onco.13857. Epub 2021 Jun 25. PMID: 34105207; PMCID: PMC8488800.
20: Wang G, Sun M, Jiang Y, Zhang T, Sun W, Wang H, Yin F, Wang Z, Sang W, Xu J, Mao M, Zuo D, Zhou Z, Wang C, Fu Z, Wang Z, Duan Z, Hua Y, Cai Z. Anlotinib, a novel small molecular tyrosine kinase inhibitor, suppresses growth and metastasis via dual blockade of VEGFR2 and MET in osteosarcoma. Int J Cancer. 2019 Aug 15;145(4):979-993. doi: 10.1002/ijc.32180. Epub 2019 Feb 15. PMID: 30719715.
