Home Protein Tyrosine Kinase VEGFR inhibitor Anlotinib (AL3818) dihydrochloride For research use only.

Anlotinib (AL3818) dihydrochloride

Anlotinib (AL3818) is a highly potent and selective VEGFR2 inhibitor with IC50 less than 1 nM. It has broad-spectrum antitumor potential in clinical trials. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation.

Anlotinib (AL3818) dihydrochloride Chemical Structure

Anlotinib (AL3818) dihydrochloride Chemical Structure

CAS: 1360460-82-7

Selleck's Anlotinib (AL3818) dihydrochloride has been cited by 33 publications

Purity & Quality Control

Batch: Purity: 99.93%
99.93

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
U-87MG Function assay 0.01, 0.1, 1, 10 and 100 μM 1.5 h inhibited PDGF-BB-stimulated phosphorylation of PDGFRβ, AKT and ERK in U-87MG cells 29446853
Mo7e Function assay 0.01, 0.1, 1, 10 and 100 μM 1.5 h Anlotinib inhibited SCF‐1‐stimulated phosphorylation of c‐Kit, AKT and ERK in Mo7e cells 29446853
HUVEC Function assay 0.01, 0.1, 1, 10 and 100 μM 1.5 h anlotinib inhibited VEGF‐stimulated intracellular phosphorylation of VEGFR2 in a concentration‐dependent way in HUVEC with a subnanomolar IC50 value 29446853
A549 Cell viability assay 24, 48 and 72 h IC50=64.82 μM（t=24 h）; IC50=30.34 μM（t=48 h）; IC50=17.29 μM（t=72 h） 30755242
NCI-H1975 Cell viability assay 8 μg/ml 24 h Cell viability was decreased remarkably 30871526
Calu-1 Cell viability assay 24, 48 and 72 h IC50=61.23 μM（t=24 h）; IC50=36.8 μM（t=48 h）; IC50=28.64 μM（t=72 h） 30755242
Click to View More Cell Line Experimental Data

Biological Activity

Description Anlotinib (AL3818) is a highly potent and selective VEGFR2 inhibitor with IC50 less than 1 nM. It has broad-spectrum antitumor potential in clinical trials. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation.
Targets
VEGFR2 [1]
(Cell-free assay)		 VEGFR3 [1]
(Cell-free assay)		 c-Kit [1]
(Cell-free assay)		 c-Kit [1]
(Cell-free assay)		 c-Kit [1]
(Cell-free assay)
0.2 nM 0.7 nM 14.8 nM 14.8 nM 14.8 nM
In vitro
In vitro Anlotinib occupies the ATP-binding pocket of VEGFR2 tyrosine kinase and shows high selectivity and inhibitory potency (IC 50 <1 nmol/L) for VEGFR2 relative to other tyrosine kinases. Anlotinib inhibits VEGFR2 and VEGFR3 with IC50 values of 0.2 and 0.7 nmol/L, respectively. The inhibitory potency of anlotinib against VEGFR1 is lower, with an IC50 value of 26.9 nmol/L. The IC50 values of anlotinib for inhibition of the PDGFR-related kinases c-Kit and PDGFRβ are 14.8 and 115.0 nmol/L, respectively. Anlotinib has little effect on the activity of other kinases, including c-Met, c-Src, EGFR and HER2, even at a concentration of 2000 nmol/L. Anlotinib inhibits VEGF-induced signaling and cell proliferation in HUVEC with picomolar IC50 values. However, micromolar concentrations of anlotinib are required to inhibit tumor cell proliferation directly in vitro. Anlotinib significantly inhibits HUVEC migration and tube formation; it also inhibits microvessel growth from explants of rat aorta in vitro[1].
Kinase Assay Enzyme-linked immunosorbent assay
Inhibitory activity of anlotinib against tyrosine kinases was determined using ELISA. 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.
Cell Research Cell lines HUVEC, Mo7e, U-87MG and A431 cells
Concentrations 0-10 μM
Incubation Time 1.5 h
Method

Serum-starved HUVEC, Mo7e, U-87MG and A431 cells are treated with different concentrations of test agents for 1.5 h and then stimulated with vascular endothelial growth factor (VEGF; 20 ng/mL), stem cell factor-1 (SCF-1; 2.5 ng/mL), platelet-derived growth factor-BB (PDGF-BB; 10 ng/mL), or epidermal growth factor (EGF; 10 ng/mL) for 10 min, respectively. Cell lysates are probed with the indicated antibodies.
Experimental Result Images Methods Biomarkers Images PMID
Western blot TP53 / Cleaved-caspase 3 / Cleaved PARP Beclin-1 / LC3-I / LC3-II Akt / p-Akt / mTOR / p-mTOR 30139768
Immunofluorescence LC3-II 30755242
Growth inhibition assay Cell viability 30755242
In Vivo
In vivo Anlotinib decreases vascular density in tumor tissue in vivo. Compared with the well-known tyrosine kinase inhibitor sunitinib, once-daily oral dose of anlotinib shows broader and stronger in vivo antitumor efficacy and, in some models, causes tumor regression in nude mice. It is well-tolerated in mice. Anlotinib is efficacious at doses (1.5‐6 mg/kg daily) that are significantly lower than effective doses of other TKI, which require doses of 20‐100 mg/kg to achieve significant inhibition of tumor growth in mice[1]. In vivo, anlotinib has showed broad activity against human tumor xenograft models of the colon (SW-620), ovarian (SK-OV-3), liver (SMMC-7721), renal (Caki-1), glioma (U87MG), and non-small cell lung (Calu-3) during dosing period. In Sprague-Dawley rats and beagle dogs, anlotinib is rapidly absorbed from the gastrointestinal tracks after oral administration. The oral bioavailability is 23-45 % in rats and 47-74 % in dogs. Anlotinib exhibits large volume of distribution in both species. In rats, primary tissues, such as the lung, kidneys, liver, and heart, exhibit significant higher exposure levels to anlotinib compared with that in plasma. The exposure level in the brain is comparable with the corresponding plasma level. In tumor-bearing mice, anlotinib concentrates 2.4-2.6 times in tumor tissue than in plasma. In human, anlotinib exhibits a quite long t1/2 (96 ± 17 h), which appeared to be dose-independent[2]. The terminal half-life of anlotinib in dogs (22.8±11.0 h) is longer than that in rats (5.1±1.6 h). This difference appeares to be mainly associated with an interspecies difference in total plasma clearance (rats, 5.35±1.31 L/h/kg; dogs, 0.40±0.06 L/h/kg). In human plasma, anlotinib is predominantly bound to albumin and lipoproteins, rather than to α1-acid glycoprotein or γ-globulins[3].
Animal Research Animal Models human colon cancer SW620 xenograft model（Balb/cA-nude mice, 5-6 weeks old)
Dosages 0.75, 1.5, 3 and 6 mg/kg
Administration oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06015061 Recruiting Pheochromocytoma Metastatic|Ultrasonography|Paraganglioma Malignant|Pheochromocytoma Malignant Peking Union Medical College Hospital March 1 2023 --
NCT05816499 Recruiting NSCLC Stage IV|NSCLC Stage IIIB|NSCLC Stage IIIC Shanghai Chest Hospital|The Affiliated Hospital of Qingdao University|Anhui Provincial Hospital|Zhejiang University February 16 2023 Phase 1|Phase 2
NCT05883085 Recruiting Pheochromocytoma|Paraganglioma Peking Union Medical College Hospital May 1 2022 Phase 2
NCT05301764 Recruiting Soft Tissue Sarcoma Lyvgen Biopharma Holdings Limited May 25 2022 Phase 1|Phase 2
NCT04803851 Recruiting Anlotinib|Anti-PD-1 Antibody|Advanced Pancreatic Cancer Peking Union Medical College Hospital May 12 2021 Phase 1|Phase 2

Chemical lnformation & Solubility

Molecular Weight 480.36 Formula

C23H22FN3O3.2HCl
CAS No. 1360460-82-7 SDF --
Smiles CC1=CC2=C(N1)C=CC(=C2F)OC3=C4C=C(C(=CC4=NC=C3)OCC5(CC5)N)OC.Cl.Cl
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

Water : 96 mg/mL

DMSO : 48 mg/mL ( (99.92 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : Insoluble


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