compound 36 [PMID: 21958547]   Click here for help

GtoPdb Ligand ID: 9391

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 36 is a selective and irreversible small molecule inhibitor of Bruton's tyrosine kinase (BTK) [1]. The compound is being studied for potential to treat rheumatoid arthritis, having been assessed as effective in preclinical models of the disease.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 65.76
Molecular weight 438.25
XLogP 3.69
No. Lipinski's rules broken 0
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Canonical SMILES CN(CC=CC(=O)N(C1CC2C(CC1F)N=C(c1n2cnc1)Nc1ccccc1C)C)C
Isomeric SMILES CN(C/C=C/C(=O)N(C1CC2C(CC1F)N=C(c1n2cnc1)Nc1ccccc1C)C)C
InChI InChI=1S/C24H31FN6O/c1-16-8-5-6-9-18(16)27-24-22-14-26-15-31(22)21-13-20(17(25)12-19(21)28-24)30(4)23(32)10-7-11-29(2)3/h5-10,14-15,17,19-21H,11-13H2,1-4H3,(H,27,28)/b10-7+
Bioactivity Comments
In B cell proliferation assays compound 36 inhibits proliferation with an IC50 of 3.41nM [1]. Compound 36 inhibits EGFR with an IC50 of 1.4nM, if a pre-incubation step is included in the assay. The same pre-incubation reduces BTK inhibition from 1.93nM (IC50 ) to 0,7nM.
The kinact/KI value (a measure of the efficiency of covalent inhibitors) for BTK is 53200 (1/M-s) and for EGFR is 101000 (1/M-s), suggesting that compound 36 could potentially inhibit EGFR in cells and tissues.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Bruton tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 8.7 pIC50 - 1
pIC50 8.7 (IC50 1.93x10-9 M) [1]
SRC proto-oncogene, non-receptor tyrosine kinase Hs Inhibitor Inhibition 6.5 pIC50 - 1
pIC50 6.5 (IC50 2.98x10-7 M) [1]
LYN proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.2 pIC50 - 1
pIC50 6.2 (IC50 6.24x10-7 M) [1]
LCK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.1 pIC50 - 1
pIC50 6.1 (IC50 7.72x10-7 M) [1]