ホームページ Protein Tyrosine Kinase VEGFR inhibitor - CSF-1R inhibitor - PDGFR inhibitor - FLT3 inhibitor - Autophagy activator - Apoptosis related activator Linifanib (ABT-869) For research use only.

Linifanib (ABT-869)

別名：AL39324,RG3635

Linifanib (ABT-869, AL39324, RG3635) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively, mostly effective in mutant kinase-dependent cancer cells (i.e. FLT3). Linifanib (ABT-869) induces autophagy and apoptosis. Phase 3.

Linifanib (ABT-869)化学構造

CAS No. 796967-16-3

サイズ 価格(税別) 在庫状況
JPY 18000 国内在庫あり
JPY 31500 国内在庫あり
JPY 85500 国内在庫あり
JPY 595500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール：[email protected]
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Linifanib (ABT-869)関連製品

シグナル伝達経路

VEGFR Signaling Pathways

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
Sf9 insect cells Function assay 120 mins Inhibition of recombinant GST-tagged VEGFR2 expressed in Sf9 insect cells after 120 mins by Kinase-Glo assay, IC50=5 nM 21708468
human MOLM13 cells Cytotoxicity assay 72 h Cytotoxicity against human MOLM13 cells harboring mutant FLT3 after 72 hrs by MTS assay, GI50=0.037 μM 23618709
human MV4-11 cells Proliferation assay 72 h Antiproliferation activity against FLT3/ITD harboring human MV4-11 cells after 72 hrs by MTS method, GI50=0.04 μM 21708468
human MOLT4 cells Proliferation assay 72 h Antiproliferation activity against human MOLT4 after 72 hrs by MTS method, GI50=6.7 μM 21708468
RS4:11 cells Proliferation assay 72 h Antiproliferation activity against human RS4:11 cells expressing wild type FLT3 after 72 hrs by MTS method, GI50=9.2 Μm 21708468
U937 cells Proliferation assay 72 h Antiproliferation activity against human FLT3 gene-deficient U937 cells after 72 hrs by MTS method, GI50=19 μM 21708468
mouse 3T3 cells Function assay Inhibition of VEGF-induced human KDR phosphorylation in mouse 3T3 cells by ELISA, IC50=0.004 μM 17343372
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生物活性

製品説明 Linifanib (ABT-869, AL39324, RG3635) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively, mostly effective in mutant kinase-dependent cancer cells (i.e. FLT3). Linifanib (ABT-869) induces autophagy and apoptosis. Phase 3.
Targets
VEGFR1/FLT1 [1]
(Cell-free assay)		 CSF-1R [1]
(Cell-free assay)		 VEGFR2/KDR [1]
(Cell-free assay)		 FLT3 [1]
(Cell-free assay)		 Kit [1]
(Cell-free assay)		 もっとクリックする
3 nM 3 nM 4 nM 4 nM 14 nM
In Vitro
In vitro Linifanib shows inhibitory to Kit, PDGFRβ and Flt4 with IC50 of 14 nM, 66 nM and 190 nM in kinases assay. Linifanib also inhibits ligand-induced KDR, PDGFRβ, Kit, and CSF-1R phosphorylation with IC50 of 2 nM, 2 nM, 31 nM and 10 nM at cellular level and this cellular potency could be affected by serum protein. Linifanib suppresses VEGF-stimulated HUAEC proliferation with IC50 of 0.2 nM. While Linifanib has weak activity against tumor cells which are not induced by VEGF or PDGF, except for MV4-11 leukemia cells (with constitutively active form of Flt3) with IC50 of 4 nM. Linifanib could cause a decrease in S and G2-M phases with a corresponding increase in the sub-G0-G1 apoptotic population in MV4-11 cells. [1] Linifanib binds to the ATP-binding site of CSF-1R with Ki of 3 nM. [2] Linifanib (10 nM) exhibits a reduced phosphorylation of Akt at Ser473 and decreased phosphorylation of GSK3βat Ser9 in Ba/F3 FLT3 ITD cell lines. [3]
Kinase Assay Kinase assays
Potencies (IC50 values) are determined by assays of active kinase domains cloned and expressed in baculovirus using the FastBacbaculovirus expression system or obtained commercially. For tyrosine kinase assays, a biotinylated peptide substrate containing a single tyrosine is used with 1 mM ATP, anEu-cryptate–labeled anti-phosphotyrosine antibody (PT66), and Strepavidin-APC in a homogeneous time-resolved fluorescence assay. Serine/threonine kinases are assayed using 5 μM ATP, [33P]ATP, and a biotinylated peptide substrate with peptide capture and incorporation of 33P determined using a SA-Flashplate. Linifanib is assayed at multiple concentrations prepared by serial dilution of a DMSO stock solution of Linifanib. The concentration resulting in 50% inhibition of activity is calculated using nonlinear regression analysis of the concentration response data.
細胞実験 細胞株 HUAEC, HT-29, HT1080, A431, MDA-435, MDA-231, H526, DLD-1, 9L and MV4-11 cells
濃度 0-100 μM
反応時間 72 hours
実験の流れ Cells are seeded into 96-well plates at 2.5 × 103 per well and incubated with serum-free medium for 24 hours. Linifanib and VEGF (final, 10 ng/mL) are added and incubated for 72 hours in serum-free medium. For carcinoma cell lines, 3 × 103 cells/well are plated overnight in full growth medium. Linifanib is added to the cells in full growth medium and incubated for 72 hours. For leukemia cells, generally 5 × 104 per well are plated in full growth medium, Linifanib is added, and incubated for 72 hours. The effects on proliferation are determined by addition of Alamar Blue (final solution, 10%), incubation for 4 hours at 37 °C in a CO2 incubator and analysis in a fluorescence plate reader (544 nm, excitation: 590 nm, emission
実験結果図 Methods Biomarkers 結果図 PMID
Western blot phospho-FLT3 / FLT3 Beclin-1 / ATG5 / ATG7 / p62 p-PDGFRβ / PDGFRβ/ p-AKT / AKT / p-mTOR / mTOR / p-S6K 21471285
Immunofluorescence LC3 25327881
In Vivo
In Vivo Linifanib (0.3 mg/kg) results in complete inhibition of KDR phosphorylation in lung tissue. Linifanib also inhibits the edema response with ED50 of 0.5 mg/kg. Linifanib (7.5 and 15 mg/kg, bid) significantly inhibits both bFGF- and VEGF-induced angiogenesis in the cornea. Linifanib inhibits tumor growth in flank xenograft models including HT1080, H526, MX-1 and DLD-1 with ED75 from 4.5-12 mg/kg. Linifanib also shows efficacy in A431 and MV4-11 xenografts at low dose levels. Linifanib (12.5 mg/kg bid) reveals a decrease of microvasculure density in MDA-231 xenograft. Linifanib shows a Cmax and AUC24 hours with 0.4 μg/mL and 2.7 μg•hour/mL in HT1080 fibrosarcoma model. [1]
動物実験 動物モデル H526, DLD-1, MDA-231, MDA-435LM, HCT-116, H526, DLD-1, MDA-231, MDA-435LM, MV4-11 and MX-1 xenografts are established in mice.
投与量 ~ 10 mg/kg
投与経路 Oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01401933 Completed
Advanced Solid Tumors
Abbott
 May 2011 Phase 1
NCT01381341 Completed
Advanced Solid Tumors
Abbott
 May 2011 Phase 1
NCT01114191 Completed
Solid Tumors
Abbott
 May 2010 Phase 1

化学情報

分子量 375.41 化学式

C21H18FN5O
CAS No. 796967-16-3 SDF Download Linifanib (ABT-869) SDFをダウンロードする
Smiles CC1=CC(=C(C=C1)F)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)NN=C4N
保管

In vitro
Batch:

DMSO : 75 mg/mL ( (199.78 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。)

Water : Insoluble

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 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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