NVP-TAE684   Click here for help

GtoPdb Ligand ID: 5714

Synonyms: NVP-TAE 684 | TAE-684 | TAE684
PDB Ligand
Compound class: Synthetic organic
Comment: NVP-TAE684 is a next-generation inhibitor designed to inhibit oncogenic ALK-rearranged fusion proteins involved in certain cancers. It was initially identified as a potent and selective inhibitor of the NPM-ALK fusion [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 111.31
Molecular weight 613.26
XLogP 5.55
No. Lipinski's rules broken 1
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Canonical SMILES COc1cc(ccc1Nc1ncc(c(n1)Nc1ccccc1S(=O)(=O)C(C)C)Cl)N1CCC(CC1)N1CCN(CC1)C
Isomeric SMILES COc1cc(ccc1Nc1ncc(c(n1)Nc1ccccc1S(=O)(=O)C(C)C)Cl)N1CCC(CC1)N1CCN(CC1)C
InChI InChI=1S/C30H40ClN7O3S/c1-21(2)42(39,40)28-8-6-5-7-26(28)33-29-24(31)20-32-30(35-29)34-25-10-9-23(19-27(25)41-4)37-13-11-22(12-14-37)38-17-15-36(3)16-18-38/h5-10,19-22H,11-18H2,1-4H3,(H2,32,33,34,35)
Bioactivity Comments
In vitro experiments using NVP-TAE684 with Karpas-299 cells (a cell line isolated from ALK-positive ALCL tumors expressing the NPM-ALK fusion) and SU-DHL-1 cells provides IC50 values in the 2-5nM range for anti-proliferative effect [2-3]. Apart from the data from HTS screens of kinase inhibitors we have been unable to find affinity data for this compound measured with recombinant ALK protein.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
ALK receptor tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 9.0 pKd - 1
pKd 9.0 (Kd 1.1x10-9 M) [1]