Anlotinib (AL3818) dihydrochloride

製品コード：S8726 純度：99.93%

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.

CAS No. 1360460-82-7

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 70500	国内在庫あり
100mg	JPY 145500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（36）

製品安全説明書

現在のバッチを見る：純度： 99.93%

99.93

Anlotinib (AL3818) dihydrochloride関連製品

関連ターゲット	VEGFR1 VEGFR2 VEGFR3	もっと見る
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関連化合物ライブラリー	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	もっと見る

シグナル伝達経路

VEGFR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
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

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
Kinase 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 t_1/2 (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
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT06331169	Not yet recruiting	Breast Cancer	Fudan University	April 1 2024	Phase 1
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

参考
[1] Xie C, et al. Cancer Sci. 2018, 109(4):1207-1219. [2] Sun Y, et al. J Hematol Oncol. 2016, 9(1):105. [3] Zhong CC, et al. Acta Pharmacol Sin. 2018, 39(6):1048-1063.

参考

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	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3 years -20°C powder	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

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
=	×	×

希釈計算器分子量計算器

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）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

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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