abivertinib   Click here for help

GtoPdb Ligand ID: 10044

Synonyms: AC0010 | AC0010MA | avitinib (superceded INN)
Compound class: Synthetic organic
Comment: Abivertinib (AC0010) is an orally active, irreversible EGFR inhibitor that selectively targets mutated EGFRs, and was designed to overcome T790M-induced resistance in tumours [2]. It may also inhibit BTK, thus offering extended clinical utility [3]. We show the structure for the free base form of the compound.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 98.41
Molecular weight 487.21
XLogP 4.44
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES C=CC(=O)Nc1cccc(c1)Oc1nc(Nc2ccc(c(c2)F)N2CCN(CC2)C)nc2c1cc[nH]2
Isomeric SMILES C=CC(=O)Nc1cccc(c1)Oc1nc(Nc2ccc(c(c2)F)N2CCN(CC2)C)nc2c1cc[nH]2
InChI InChI=1S/C26H26FN7O2/c1-3-23(35)29-17-5-4-6-19(15-17)36-25-20-9-10-28-24(20)31-26(32-25)30-18-7-8-22(21(27)16-18)34-13-11-33(2)12-14-34/h3-10,15-16H,1,11-14H2,2H3,(H,29,35)(H2,28,30,31,32)
InChI Key UOFYSRZSLXWIQB-UHFFFAOYSA-N
Bioactivity Comments
AC0010 inhibits EGFR-active and T790M mutations with an almost 300-fold increase in potency over wild-type EGFR [2]. It inhibits the EGFR L858R/T790M double mutatant with an IC50 value of 0.18 nM. In biochemical assays AC0010 potently inhibits BTK and JAK3, however the JAK3 inhibition translates poorly in cellular assays. Note that some bioactivities may have been determined using AC0010 maleate as depicted in [2], and by PubChem CID 121596128.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 3 Hs Inhibitor Inhibition 10.1 pIC50 - 2
pIC50 10.1 (IC50 9x10-11 M) [2]
Description: In a biochemical assay.
Bruton tyrosine kinase Hs Inhibitor Inhibition 9.4 pIC50 - 2
pIC50 9.4 (IC50 4x10-10 M) [2]
Description: In a biochemical assay.
Selectivity at catalytic receptors
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
epidermal growth factor receptor Hs Inhibitor Inhibition 8.1 pIC50 - 2
pIC50 8.1 (IC50 7.68x10-9 M) [2]
Description: In a biochemical assay.