Anlotinib HCl | AL3818 | CAS#1058156-90-3 | 1360460-82-7 | RTK inhibitor

MedKoo Cat#: 206058 | Name: Anlotinib HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Anlotinib HCl

CAS#1360460-82-7 (HCl)

Theoretical Analysis

MedKoo Cat#: 206058

Name: Anlotinib HCl

CAS#: 1360460-82-7 (HCl)

Chemical Formula: C23H24Cl2FN3O3

Exact Mass: 0.0000

Molecular Weight: 480.36

Elemental Analysis: C, 57.51; H, 5.04; Cl, 14.76; F, 3.96; N, 8.75; O, 9.99

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,950.00	Ready to Ship
1g	USD 4,350.00	Ready to Ship

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Related CAS #

1058156-90-3 (free base) 1360460-82-7 (HCl)

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

More Info

Related CAS# 1058156-90-3 (Anlotinib) 1360460-82-7 (Anlotinib Dihydrochloride)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C8R11B08

QC Data

View QC data: current batch, Lot#C8R11B08

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	54.0	112.42
	Water	96.0	199.85

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 480.36 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:

In vivo protocol:

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.