NVP-TAE-684-TAE-684-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENVP-TAE 684Cat. No.: HY-10192CAS No.: 761439-42-3Synonyms: TAE 684分式: CHClNOS分量: 614.2作靶點(diǎn): ALK作通路: Protein Tyrosine Kinase/RTK儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 7.69 mg/mL (12.

2、52 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.6281 mL 8.1407 mL 16.2813 mL5 mM 0.3256 mL 1.6281 mL 3.2563 mL10 mM 0.1628 mL 0.8141 mL 1.6281 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。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清

3、的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.77 mg/mL (1.25 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.77 mg/mL (1.25 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLO

4、GICAL ACTIVITY物活性 NVP-TAE 684種效的，選擇性的 ALK 抑制劑，阻 ALCL 衍的 ALK 依賴性細(xì)胞株的長，IC50 值為2-10 nM。體外研究 TAE684 inhibits the proliferation of Ba/F3 NPM-ALK cells with an ICsub50 of 3 nM, without affecting thesurvival of parental Ba/F3 cells at concentrations up to 1 M. TAE684 inhibits STAT3 and STAT5phosphorylation

5、 in a dose-dependent manner in both Ba/F3 NPM-ALK and Karpas-299 cells. TAE684induces apoptosis and G1 phase arrest in NPM-ALK-expressing Ba/F3 cells and ALCL patient cell lines 1.NVP-TAE684 markedly reduces cell survival in both sensitive H3122 and H3122 CR cells, but has little to noeffect on the

6、viability of other, non-ALK-dependent cancer cell lines. NVP-TAE684 treatment of H3122 CRcells suppresses phosphorylation of ALK, AKT, and ERK and induces marked apoptosis. TAE684 potentlysuppresses the survival of Ba/F3 cells expressing the EML4-ALK L1196M mutant 2. Neurite outgrowthinduced by expr

7、ession of the mALKR1279Q mutant is completely inhibited at 30 nM NVP-TAE684, which iscomparable with the response seen with activated wt mALK 3.體內(nèi)研究 NVP-TAE684 suppresses lymphomagenesis in two independent models of ALK-positive ALCL and inducesregression of established Karpas-299 lymphomas. TAE684

8、displays appreciable bioavailability and half-life invivo. TAE684 (1, 3, and 10 mg/kg. p.o.) significantly delays in lymphoma development and shows 100- to1,000-fold reduction in luminescence signal. The TAE684- (10 mg/kg) treated group appeares healthy anddoes not display any signs of compound- or

9、disease-related toxicity 1.PROTOCOLCell Assay 1 Luciferase-expressing Karpas-299, SU-DHL-1, and Ba/F3 cells and transformed Ba/F3 stably expressingNPM-ALK, BCR-ABL, or TEL-kinase fusion constructs are plated in 384-well plates (25,000 cells per well)and incubated with serial dilutions of TAE684 or D

10、MSO for 2-3 days. Luciferase expression is used as ameasure of cell proliferation/survival and is evaluated with the Bright-Glo Luciferase Assay System.ICsub50 values are generated by using XLFit software.MCE has not independently confirmed the accuracy of these methods. They are for reference only.

11、Animal For in vivo compound efficacy studies, treatment is initiated 72 h after tail vein injection of 1106 Karpas-299-Administration 1 , Ba/F3 NPM-ALK- or BCR-ABL-expressing cells into female Fox Chase SCIDBeige mice. Mice (n=10 pergroup) are administered either TAE684 resuspended in 10% 1-methyl-2

12、-pyrrolidinone/90% PEG 300 solutionat 1, 3, and 10 mg/kg once daily for 3 weeks or the vehicle solution at the same dosing schedule. Diseaseprogression and compound efficacy is monitored weekly with bioluminescence imaging. To determine theefficacy of TAE684 on established disease, dosing is initiat

13、ed on day 12, at which time the disease confirmedto be widespread by bioluminescence imaging. For analysis of downstream molecular effects in vivo, micewith established lymphomas are administered vehicle solution or TAE684 (10 mg/kg) for 3 days. At the endof treatment, mice are killed, and lymph nod

14、es are extracted for immunoblotting and histological analysis.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 Molecules 您邊的抑制劑師www.MedChemE Cell Chem Biol. 2018 Feb 15;25(2):224-229.e2. BMC Biol. 2018 Sep 5;16(1):90. ACS C

15、hem Biol. 2012 Dec 21;7(12):1968-74. Pigment Cell Melanoma Res. 2019 May;32(3):391-402. Pigment Cell Melanoma Res. 2016 May;29(3):284-96.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Galkin AV, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibito

16、r of NPM-ALK. Proc Natl Acad Sci U S A.2007 Jan 2;104(1):270-5.2. Katayama R, et al. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusiononcogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40.3. Schonherr C, Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-