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化学構造

CAS No. 1360460-82-7

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 29000 国内在庫あり
JPY 23100 国内在庫あり
JPY 69600 国内在庫あり
JPY 144600 国内在庫なし(納期7~10日)

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Anlotinib (AL3818) dihydrochloride関連製品

シグナル伝達経路

VEGFR阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
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
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
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
NCI-H1975 Cell viability assay 8 μg/ml 24 h Cell viability was decreased remarkably 30871526
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
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
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生物活性

製品説明 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.
細胞実験 細胞株 HUVEC, Mo7e, U-87MG and A431 cells
濃度 0-10 μM
反応時間 1.5 h
実験の流れ

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.

実験結果図 Methods Biomarkers 結果図 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].
動物実験 動物モデル human colon cancer SW620 xenograft model(Balb/cA-nude mice, 5-6 weeks old)
投与量 0.75, 1.5, 3 and 6 mg/kg
投与経路 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

化学情報

分子量 480.36 化学式

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
保管 3 years -20°C powder

In vitro
Batch:

Water : 96 mg/mL

DMSO : 48 mg/mL ( (99.92 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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