Purity: ≥98%
Anlotinib (formerly known as AL3818) is a novel and potent multi-kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFRα/β, c-Kit, and Ret. Anlotinib as a receptor tyrosine kinase (RTK) inhibitor has potential antineoplastic and anti-angiogenic activities. Anlotinib significantly reduces AN3CA cell number in vitro, characterized by high expression of a mutated FGFR2 protein. Daily oral administration of Anlotinib (5 mg/kg) resulted in a complete response in 55% of animals treated and in a reduced tumor volume, as well as decreased tumor weights of AN3CA tumors by 94% and 96%, respectively, following a 29-day treatment cycle. Whereas carboplatin and paclitaxel failed to alter tumor growth, the combination with Anlotinib did not seem to exhibit a superior effect when compared with Anlotinib treatment alone.
| Targets |
VEGFR2 (IC50 = 0.2 nM); VEGFR3 (IC50 = 0.7 nM); c-Kit (IC50 = 14.8 nM); c-Kit (IC50 = 14.8 nM); c-Kit (IC50 = 14.8 nM)
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| ln Vitro |
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| Enzyme Assay |
Anlotinib (formerly known as AL3818) is a novel and powerful multi-kinase inhibitor that blocks Ret, FGFR1-4, PDGFRα/β, c-Kit, and VEGFR2/3.
Inhibitory activity of anlotinib against tyrosine kinases was determined using ELISA, as described previously.22 Reaction of ATP with tyrosine kinase was initiated in reaction buffer (50 mmol/L HEPES pH 7.4, 50 mmol/L MgCl2, 0.5 mmol/L MnCl2, 0.2 mmol/L Na3VO4, 1 mmol/L DTT) and incubated for 1 hour at 37°C in 96‐well plates precoated with 20 μg/mL Poly(Glu,Tyr)4:1. The plate was incubated with PY99 antibody and then with HRP‐conjugated anti‐mouse IgG. After reaction with o‐phenylenediamine solution and then termination with the addition of 2N H2SO4, absorbance was measured at 490 nm using a Synergy H4 Hybrid reader[3]. |
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| Cell Assay |
In vitro, AL3818 dramatically lowers the number of AN3CA cells, which are identified by the high expression of a mutant FGFR2 protein. After a 29-day treatment cycle, daily oral administration of AL3818 (5 mg/kg) resulted in a complete response in 55% of treated animals and in a reduction of tumor volume and tumor weights of AN3CA tumors by 94% and 96%, respectively. When compared to AL3818 treatment alone, the combination of carboplatin and paclitaxel did not appear to have a greater effect, despite their inability to change the growth of the tumor.
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| Animal Protocol |
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| References |
[3]. Cancer Sci . 2018 Apr;109(4):1207-1219.
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| Additional Infomation |
Anlotinib has been investigated for the treatment of Non-small Cell Lung Cancer and Metastatic Colorectal Cancer.
Catequentinib is a receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic and anti-angiogenic activities. Upon administration, catequentinib 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. Drug Indication Treatment of Ewing sarcoma, Treatment of soft tissue sarcomas |
| Molecular Formula |
C23H22FN3O3
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| Molecular Weight |
407.45
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| Exact Mass |
407.16
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| Elemental Analysis |
C, 67.80; H, 5.44; F, 4.66; N, 10.31; O, 11.78
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| CAS # |
1058156-90-3
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| Related CAS # |
1058156-90-3;1360460-82-7 (HCl);
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| PubChem CID |
25017411
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| Appearance |
Solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
606
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KSMZEXLVHXZPEF-UHFFFAOYSA-N
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| 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
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| Chemical Name |
1-[[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinolin-7-yl]oxymethyl]cyclopropan-1-amine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4543 mL | 12.2714 mL | 24.5429 mL | |
| 5 mM | 0.4909 mL | 2.4543 mL | 4.9086 mL | |
| 10 mM | 0.2454 mL | 1.2271 mL | 2.4543 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03890068 | Recruiting | Drug: Anlotinib Hydrochloride | Soft Tissue Sarcoma | Sun Yat-sen University | August 5, 2020 | Phase 2 |
| NCT05602415 | Recruiting | Drug: Anlotinib Procedure: Surgery |
Anlotinib Radiotherapy |
Ruijin Hospital | November 2022 | Phase 2 |
| NCT05883085 | Recruiting | Drug: Anlotinib hydrochloride | Pheochromocytoma Paraganglioma |
Peking Union Medical College Hospital |
May 1, 2022 | Phase 2 |
| NCT05218629 | Recruiting | Drug: Anlotinib, PD-1 inhibitor | Overall Survival | Qingdao Central Hospital | January 1, 2022 | Phase 2 |
| NCT05866510 | Recruiting | Drug: Utidelone and anlotinib | Esophageal Cancer | Peking University | May 15, 2023 | Phase 2 |
The lung metastasis changes in patients of alveolar soft tissue sarcoma with lung metastasis during treatment.J Hematol Oncol.2016 Oct 4;9(1):105. |
Duration of treatment and tumor size changes of 20 patients who received 12mg QD at the 2/1 schedule. J Hematol Oncol.2016 Oct 4;9(1):105. |
Plasma concentrations of anlotinib over time after a single oral dose of anlotinib capsules at 5 (green line), 10 (purple line), 12 (blue line), or 16mg anlotinib/person (red line) in male (solid circles) and female cancer patients (open circles) (a).bCorrelation of dose with plasma AUC0–120h.cCorrelation of dose with plasmaCmax.dCorrelation of dose witht1/2.ePlasma concentrations of anlotinib (24h after daily dosing) over time during multiple oral doses of anlotinib capsules at 12mg anlotinib/person/day in female cancer patients.fPlasma concentrations of anlotinib (24h after daily dosing) over time during multiple oral doses of anlotinib capsules at 12mg anlotinib/person/day in male cancer patients.J Hematol Oncol.2016 Oct 4;9(1):105. |
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