compound 25 [PMID: 31260299]   Click here for help

GtoPdb Ligand ID: 10428

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 25 is a potent, selective and reversible inhibitor of Bruton's tyrosine kinase (BTK) [2]. It is built on a 4-aminoquinoline scaffold, and has improved drug-like properties (aqueous solubility, potency and stability) compared to previously reported cinnoline scaffold compounds [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 3
Topological polar surface area 119.91
Molecular weight 351.11
XLogP 2.77
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc2cn[nH]c2cc1c1ccc(c2c1ncc(c2N)C(=O)N)F
Isomeric SMILES COc1cc2cn[nH]c2cc1c1ccc(c2c1ncc(c2N)C(=O)N)F
InChI InChI=1S/C18H14FN5O2/c1-26-14-4-8-6-23-24-13(8)5-10(14)9-2-3-12(19)15-16(20)11(18(21)25)7-22-17(9)15/h2-7H,1H3,(H2,20,22)(H2,21,25)(H,23,24)
Bioactivity Comments
Compound 25 inhibits mutant BTKC481S with an IC50 of 39 nM (compared to 5.3 nM for wild type BTK) [2]. Compound 25 is > 40-fold selective for wild type BTK over TEC (IC50 227 nM), and has no effect on EGFR (these are both inhibited by ibrutinib). Inhibition of ITK by compound 25 (IC50 306 nM) suggests that it could potentially modulate T cell processes. It also has measurable inhibitory activity at some SRC family kinases.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Bruton tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 8.3 pIC50 - 2
pIC50 8.3 (IC50 5.3x10-9 M) [2]
BLK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.8 pIC50 - 2
pIC50 6.8 (IC50 1.5x10-7 M) [2]
FYN proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.8 pIC50 - 2
pIC50 6.8 (IC50 1.652x10-7 M) [2]
tec protein tyrosine kinase Hs Inhibitor Inhibition 6.6 pIC50 - 2
pIC50 6.6 (IC50 2.27x10-7 M) [2]
IL2 inducible T cell kinase Hs Inhibitor Inhibition 6.5 pIC50 - 2
pIC50 6.5 (IC50 3.069x10-7 M) [2]
SRC proto-oncogene, non-receptor tyrosine kinase Hs Inhibitor Inhibition 6.0 pIC50 - 2
pIC50 6.0 (IC50 9.025x10-7 M) [2]