bimiralisib   Click here for help

GtoPdb Ligand ID: 8383

Synonyms: PQR-309 | PQR309
PDB Ligand
Compound class: Synthetic organic
Comment: Bimiralisib (PQR309) is a novel dual inhibitor of phosphoinositol 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR) kinases, with expected utility as an anti-cancer agent (see AACR poster #2664, 2015).
The discovery of PQR309 is claimed in patent WO-2010052569-A2, where it is compound 54 (in structure tables) and Example P11 [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 9
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 102.52
Molecular weight 411.16
XLogP 1.83
No. Lipinski's rules broken 0
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 Nc1ncc(c(c1)C(F)(F)F)c1nc(nc(n1)N1CCOCC1)N1CCOCC1
Isomeric SMILES Nc1ncc(c(c1)C(F)(F)F)c1nc(nc(n1)N1CCOCC1)N1CCOCC1
InChI InChI=1S/C17H20F3N7O2/c18-17(19,20)12-9-13(21)22-10-11(12)14-23-15(26-1-5-28-6-2-26)25-16(24-14)27-3-7-29-8-4-27/h9-10H,1-8H2,(H2,21,22)
InChI Key ADGGYDAFIHSYFI-UHFFFAOYSA-N
Bioactivity Comments
PQR309 is a potent and specific ATP-competitive inhibitor of all PI3K class I isoforms and mTORC1/2 complexes (see AACR poster #2664, 2015). PQR309 exhibits antiproliferative activity on cancer cell lines (screened using the OncolineTM panel, NTRC, the Netherlands) and shows antitumour effects in xenografted mice (see AACR poster #4541, 2015). Along with this activity profile, PQR309 also has good pharmacokinetic (PK) properties and favourable safety profile making this an attractive drug candidate.
The Kd values in the table below were supplied in good faith, by Doriano Fabbro who heads up our Kinases Oversight Committee and were produced using DiscoveRx's KINOMEscanSM.
As PQR309 is equipotent at mTOR and all isoforms of PI3K we have tagged each enzyme as a primary molecular target.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha Primary target of this compound Hs Inhibitor Inhibition 8.8 pKd -
⤷ pKd 8.8 (Kd 1.5x10-9 M)
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta Primary target of this compound Hs Inhibitor Inhibition 8.0 pKd -
⤷ pKd 8.0 (Kd 1.1x10-8 M)
mechanistic target of rapamycin kinase Primary target of this compound Hs Inhibitor Inhibition 7.9 pKd -
⤷ pKd 7.9 (Kd 1.2x10-8 M)
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta Primary target of this compound Hs Inhibitor Inhibition 7.6 pKd -
⤷ pKd 7.6 (Kd 2.5x10-8 M)
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma Primary target of this compound Hs Inhibitor Inhibition 7.6 pKd -
⤷ pKd 7.6 (Kd 2.5x10-8 M)