Linifanib-ABT-869-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELinifanibCat. No.: HY-50751CAS No.: 796967-16-3Synonyms: ABT-869; AL-39324分式: CHFNO分量: 375.4作靶點(diǎn): PDGFR; VEGFR; Autophagy; FLT3作通路: Protein Tyrosine Kinase/RTK; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-

2、20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 72 mg/mL (191.80 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.6638 mL 13.3191 mL 26.6383 mL5 mM 0.5328 mL 2.6638 mL 5.3277 mL10 mM 0.2664 mL 1.3319 mL 2.6638 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVI

3、TY物活性 Linifanib (ABT-869)種多靶點(diǎn) VEGF 和 PDGFR 受體家族的抑制劑，抑制KDR，F(xiàn)lt-1，PDGFR和FLT3的IC50 值分別為3，4，66，4 nM。IC50 & Target KDR PDGFR Flt-1 FLT34 nM (IC50) 66 nM (IC50) 3 nM (IC50) 4 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Linifanib exhibits IC50 values that range from 4 nM (KDR) to 190 nM

4、(FLT4) for members of the VEGF andPDGF receptor families. Linifanib is also active against TIE2 and, to a lesser extent, RET, but is much lessactive (IC5010 M) against other nonrelated tyrosine kinases, such as steroid receptor coactivator andepidermal growth factor receptor. Phosphorylation of KDR

5、induced by VEGF is inhibited by Linifanib with anIC50 of 4 nM in 3T3 murine fibroblasts engineered to express human KDR. A similar potency for inhibition ofreceptor autophosphorylation is seen with Linifanib when HUAECs are used as the target cell. Linifanibinhibits VEGF-stimulated phosphorylation o

6、f KDR completely at 10 nM and by 70% at 3 nM (IC50=2 nM) 1.體內(nèi)研究 Linifanib is effective orally in the mechanism-based murine models of VEGF-induced uterine edema(ED50=0.5 mg/kg) and corneal angiogenesis (50% inhibition, 15 mg/kg). ABT-869 exhibits efficacy inhuman fibrosarcoma and breast, colon, and

7、small cell lung carcinoma xenograft models (ED50=1.5-5 mg/kg,twice daily) and is also effective (50% inhibition) in orthotopic breast and glioma models. Reduction in tumorsize and tumor regression is observed in epidermoid carcinoma and leukemia xenograft models, respectively1.PROTOCOLKinase Assay 1

8、 For tyrosine kinase assays, a biotinylated peptide substrate containing a single tyrosine is used with 1 mMATP, an Eu-cryptate-labeled anti-phosphotyrosine antibody (PT66), and Strepavidin-APC in a homogeneoustimeresolved fluorescence assay. Serine/threonine kinases are assayed using 5 M ATP, 33PAT

9、P, and abiotinylated 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 stocksolution of the compound. The concentration resulting in 50% inhibition of activity is cal

10、culated usingnonlinear regression analysis of the concentration response data 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 HUAEC are plated into 96-well plates at 2,500 per well and incubated with serum-free medium for 24 hours.Linifan

11、ib and VEGF(final, 10 ng/mL) are added and incubated for 72 hours in serum-free medium. Forcarcinoma cell lines, 2,500 per well are plated overnight in full growth medium. Linifanib is added to the cellsin full growth medium and incubated for 72 hours. For leukemia cells, generally 50,000 per well a

12、re plated infull growth medium, drug added, and incubated for 72 hours. The effects on proliferation are determined byaddition of Alamar Blue (final solution, 10%), incubation for 4 hours at 37jC in a CO2 incubator, and analysisin a fluorescence plate reader 1.MCE has not independently confirmed the

13、 accuracy of these methods. They are for reference only.Animal Mice: Tumor-bearing animals are divided into groups (n=10), and administration of vehicle (2% ethanol, 5%Administration 1 Tween 80, 20% PEG400, 73% saline) or inhibitor (Linifanib) at the indicted dose is initiated. Tumor growth inthe fl

14、ank is assessed by measuring tumor size with calipers and calculating size. Tumor volume for theorthotopic glioma model is determined using magnetic resonance imaging 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn)2/3 Master of Small Molec

15、ules 您邊的抑制劑師www.MedChemE Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Nat Biomed Eng. 2018;2:578-588. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Albert DH, et al. Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer T