eganelisib   Click here for help

GtoPdb Ligand ID: 9563

Synonyms: compound 26 [PMID: 27660692] | IPI-549 | IPI549
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Eganelisib (IPI549) is an orally bioavailable, highly selective small molecule PI3Kγ inhibitor [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 124.61
Molecular weight 528.2
XLogP 5.31
No. Lipinski's rules broken 1
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Canonical SMILES Cn1ncc(c1)C#Cc1cccc2c1c(=O)n(c(c2)C(NC(=O)c1c(N)nn2c1nccc2)C)c1ccccc1
Isomeric SMILES Cn1ncc(c1)C#Cc1cccc2c1c(=O)n(c(c2)[C@@H](NC(=O)c1c(N)nn2c1nccc2)C)c1ccccc1
InChI InChI=1S/C30H24N8O2/c1-19(34-29(39)26-27(31)35-37-15-7-14-32-28(26)37)24-16-22-9-6-8-21(13-12-20-17-33-36(2)18-20)25(22)30(40)38(24)23-10-4-3-5-11-23/h3-11,14-19H,1-2H3,(H2,31,35)(H,34,39)/t19-/m0/s1
Bioactivity Comments
IPI549 is >100-fold selective for PI3Kγ over the other lipid and protein kinases tested [1]. In vivo, it robustly inhibits PI3Kγ-mediated neutrophil migration. Cellular IC50s (nM; measuring inhibition of pAKT S473) are 250 (α), 240 (β), 1.2 (γ) and 180 (δ) vs. the four PI3K isozymes in SKOV-3, 786-O, RAW 264.7, and RAJI cells respectively. IPI549 inhibits migration of bone marrow derived macrophages (BMDM) with an IC50 of 85nM in vitro. It inhibits proliferation of mouse MLg2908 lung fibroblasts (IC50 980 nM) [2].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma Primary target of this compound Hs Inhibitor Inhibition 9.5 pKd - 1
pKd 9.5 (Kd 2.9x10-10 M) [1]
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha Hs Inhibitor Inhibition 7.8 pKd - 1
pKd 7.8 (Kd 1.7x10-8 M) [1]
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta Hs Inhibitor Inhibition 7.6 pKd - 1
pKd 7.6 (Kd 2.3x10-8 M) [1]
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta Hs Inhibitor Inhibition 7.1 pKd - 1
pKd 7.1 (Kd 8.2x10-8 M) [1]