Free shipping on all orders over $ 500

NVP-TAE684

Cat. No. M3781
NVP-TAE684 Structure
Size Price Availability Quantity
5mg USD 90  USD90 In stock
10mg USD 135  USD135 In stock
50mg USD 375  USD375 In stock
Free Delivery on orders over USD 500 Bulk Inquiry?

Quality Control & Documentation
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 (for reference only)
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
Chemical Information
Molecular Weight 614.2
Formula C30H40ClN7O3S
CAS Number 761439-42-3
Solubility (25°C) DMSO ≥28 mg/mL
Ethanol ≥1.8 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
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 Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.

References

[1] Zhang J, et al. Bioorg Med Chem Lett. Characterization of TAE684 as a potent LRRK2 kinase inhibitor.

[2] Schönherr C, et al. Biochem J. Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684.

[3] Galkin AV, et al. Proc Natl Acad Sci U S A. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK.

Related ALK Products
NVL-655

NVL-655 is a novel, brain-permeable, selective ALK inhibitor with antitumor activity. For Ba/F3 CLIP1-LTK cells, NVL-655 has an IC50 of 2.7 nM. It can be used in studies related to ALK-positive non-small cell lung cancer (NSCLC).

APG-2449

APG-2449 is an orally active, potent ALK/ROS1/FAK inhibitor with anti-tumor activity in a mouse model of non-small cell lung cancer (NSCLC).

ALK2-IN-5

ALK2-IN-5, pyrazolopyrimidine compound, is an ALK2 inhibitor.

J-1048

J-1048 is an activin receptor-like kinase 5 (ALK5) inhibitor.

CPD-1224

CPD-1224 is an orally active derivative of ALK inhibitors to cereblon ligands.

  Catalog
Abmole Inhibitor Catalog




Keywords: NVP-TAE684 supplier, ALK, inhibitors, activators


Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.