compound E22 [PMID: 31298542]   

GtoPdb Ligand ID: 10437

Compound class: Synthetic organic
Comment: Compound E22 is a pan-Akt (protein kinase B) inhibitor that was designed to combine anti-tumour efficacy with favourable drug-like properties [1].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 101.19
Molecular weight 525.11
XLogP 3.44
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES CNC(=O)CC1NCC(C(C1)c1ccc(c(c1)F)F)NC(=O)c1oc(c(c1)c1c(Cl)cnn1C)Cl
Isomeric SMILES CNC(=O)C[C@H]1NC[C@H]([C@@H](C1)c1ccc(c(c1)F)F)NC(=O)c1oc(c(c1)c1c(Cl)cnn1C)Cl
InChI InChI=1S/C23H23Cl2F2N5O3/c1-28-20(33)7-12-6-13(11-3-4-16(26)17(27)5-11)18(10-29-12)31-23(34)19-8-14(22(25)35-19)21-15(24)9-30-32(21)2/h3-5,8-9,12-13,18,29H,6-7,10H2,1-2H3,(H,28,33)(H,31,34)/t12-,13-,18+/m0/s1
InChI Key SXDPQGRNHSLZPC-ZJNRKIDTSA-N
Bioactivity Comments
Compound E22 inhibits tumour growth by >90% in the SKOV3 xenograft model [1]. It has good kinase selectivity and pharmacokinetic profiles, and is a poor hERG inhibitor (4% inhibition at 3 μM).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
protein kinase A Hs Inhibitor Inhibition 9.5 pIC50 - 1
pIC50 9.5 (IC50 3x10-10 M) [1]
AKT serine/threonine kinase 2 Hs Inhibitor Inhibition 8.9 pIC50 - 1
pIC50 8.9 (IC50 1.2x10-9 M) [1]
AKT serine/threonine kinase 1 Hs Inhibitor Inhibition 8.9 pIC50 - 1
pIC50 8.9 (IC50 1.37x10-9 M) [1]
AKT serine/threonine kinase 3 Hs Inhibitor Inhibition 8.8 pIC50 - 1
pIC50 8.8 (IC50 1.7x10-9 M) [1]
ribosomal protein S6 kinase B1 Hs Inhibitor Inhibition 8.1 pIC50 - 1
pIC50 8.1 (IC50 8.9x10-9 M) [1]
Rho associated coiled-coil containing protein kinase 1 Hs Inhibitor Inhibition 7.2 pIC50 - 1
pIC50 7.2 (IC50 6.4x10-8 M) [1]
ribosomal protein S6 kinase A1 Hs Inhibitor Inhibition 6.9 pIC50 - 1
pIC50 6.9 (IC50 1.31x10-7 M) [1]