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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key XUMALORDVCFWKV-IBGZPJMESA-N
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]