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NVP-TAE684

Cat. No. M3781
NVP-TAE684 Structure
Size Price Availability Quantity
5mg USD 130 In stock
10mg USD 220 In stock
50mg USD 640 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

TAE684 is a potent inhibitor of LRRK2 kinase activity (IC(50) of 7.8nM against wild-type LRRK2, 6.1nM against the G2019S mutant). TAE684 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3μM in cells and in mouse spleen and kidney, but not in brain, following oral doses of 10mg/kg. TAE684 potently inhibits the proliferation of Ba/F3 NPM-ALK cells with IC50 of 3 nM, without affecting the survival of Ba/F3 cells even at 1 μM. TAE684 also inhibits proliferation of NPM-ALK-expressing human ALCL cell lines including Karpas-299 and SU-DHL-1 with IC50 of 2–5 nM. Molecular modeling reveals that L258 may be one of the major kinase-selectivity determinants for TAE684. TAE684 treatment results in a rapid and sustained inhibition of phosphorylation of NPM-ALK. TAE684 induces apoptosis and G1 phase arrest in NPM-ALK-expressing Ba/F3 cells and ALCL patient cell lines. be one of the major kinase-selectivity determinants for TAE684. Neurite outgrowth induced by expression of the mALK R1279Q mutant could be completely inhibited by TAE684 at 30 nM.

Protocol
Cell Experiment
Cell lines Luciferase-expressing Karpas-299, SU-DHL-1, and Ba/F3 cells and transformed Ba/F3 stably expressing NPM-ALK, Bcr-Abl, or TEL-kinase fusion constructs.
Preparation method Seeding cells in 384-well plates (2.5×104 cells per well) and incubating with serial dilutions of TAE684 or DMSO for 2–3 days. Using Luciferase expression as a measure of cell proliferation/survival and evaluating with the Bright-Glo Luciferase Assay System.Using XLFit software to generate IC50 values .
Concentrations 1 nM-10 μM
Incubation time 2–3 days
Animal Experiment
Animal models Karpas-299 xenografts are established in 4- to 6-week old female Fox Chase SCIDBeige mice
Formulation Resuspended in 10% 1-methyl-2-pyrrolidinone/90% polyethylene glycol 300 solution
Dosages 1, 3, and 10 mg/kg
Administration Once daily by oral gavage for 3 weeks
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 614.2
Formula C30H40ClN7O3S
CAS Number 761439-42-3
Purity >99%
Solubility DMSO ≥28 mg/mL
Ethanol ≥1.8 mg/mL
Storage at -20°C
References

Characterization of TAE684 as a potent LRRK2 kinase inhibitor.
Zhang J, et al. Bioorg Med Chem Lett. 2012 Mar 1;22(5):1864-9. PMID: 22335897.

Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684.
Schönherr C, et al. Biochem J. 2011 Dec 15;440(3):405-13. PMID: 21838707.

Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK.
Galkin AV, et al. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. PMID: 17185414.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: NVP-TAE684 supplier, ALK, inhibitors

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