ilginatinib   

GtoPdb Ligand ID: 7839

Synonyms: NS-018 | NS018
Compound class: Synthetic organic
Comment: Ilginatinib (NS-018) is a potent and highly selective JAK2 inhibitor. It has an ATP-competitive mode of action. The chemical structure shown here was rendered from the chemical name provided in [1]. The inhibits some Src family kinases in addition to JAK2 [2].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 80.55
Molecular weight 389.18
XLogP 4.14
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES Fc1ccc(cc1)C(Nc1nc(Nc2cnccn2)cc(c1)c1cnn(c1)C)C
Isomeric SMILES Fc1ccc(cc1)[C@@H](Nc1nc(Nc2cnccn2)cc(c1)c1cnn(c1)C)C
InChI InChI=1S/C21H20FN7/c1-14(15-3-5-18(22)6-4-15)26-19-9-16(17-11-25-29(2)13-17)10-20(27-19)28-21-12-23-7-8-24-21/h3-14H,1-2H3,(H2,24,26,27,28)/t14-/m0/s1
InChI Key UQTPDWDAYHAZNT-AWEZNQCLSA-N
Bioactivity Comments
A single activating somatic mutation in JAK2 (V617F) has been identified as one of the causes of myeloproliferative neoplasms (MPNs), including primary myelofibrosis. Inhibition of this mutated enzyme would therefore be likely to show efficacy in the stated conditions. Nakaya et al (2014) [1] report that NS-018 is 4.3-fold selective in inhibiting the growth of V617F carrying cells compared to wild type JAK2 carrying cells.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 2 Hs Inhibitor Inhibition 9.1 pIC50 - 2
pIC50 9.1 (IC50 7.2x10-10 M) [2]
tyrosine kinase 2 Hs Inhibitor Inhibition 7.7 pIC50 - 2
pIC50 7.7 (IC50 2.2x10-8 M) [2]
Janus kinase 1 Hs Inhibitor Inhibition 7.5 pIC50 - 2
pIC50 7.5 (IC50 3.3x10-8 M) [2]
Janus kinase 3 Hs Inhibitor Inhibition 7.4 pIC50 - 2
pIC50 7.4 (IC50 3.9x10-8 M) [2]