PI-103   Click here for help

GtoPdb Ligand ID: 5701

Synonyms: compound 2 [PMID: 17601739] | PI 103 | PIK 103
PDB Ligand
Compound class: Synthetic organic
Comment: The discovery of PI-103 is described in [5], where it is compound 10e. It was originally identified as a PI3Kα/β inhibitor, but has subsequently been found to inhibit catalytic activity of all four PI3K subunits (α, β, γ and δ) [8].
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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 5
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 84.51
Molecular weight 348.12
XLogP 2.97
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 Oc1cccc(c1)c1nc(N2CCOCC2)c2c(n1)c1cccnc1o2
Isomeric SMILES Oc1cccc(c1)c1nc(N2CCOCC2)c2c(n1)c1cccnc1o2
InChI InChI=1S/C19H16N4O3/c24-13-4-1-3-12(11-13)17-21-15-14-5-2-6-20-19(14)26-16(15)18(22-17)23-7-9-25-10-8-23/h1-6,11,24H,7-10H2
InChI Key TUVCWJQQGGETHL-UHFFFAOYSA-N
References
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
3. Fan QW, Knight ZA, Goldenberg DD, Yu W, Mostov KE, Stokoe D, Shokat KM, Weiss WA. (2006)
A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma.
Cancer Cell, 9 (5): 341-9. [PMID:16697955]
4. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem J, 451 (2): 313-28. [PMID:23398362]
5. Hayakawa M, Kaizawa H, Moritomo H, Koizumi T, Ohishi T, Yamano M, Okada M, Ohta M, Tsukamoto S, Raynaud FI et al.. (2007)
Synthesis and biological evaluation of pyrido[3',2':4,5]furo[3,2-d]pyrimidine derivatives as novel PI3 kinase p110alpha inhibitors.
Bioorg Med Chem Lett, 17 (9): 2438-42. [PMID:17339109]
6. Hayakawa M, Kawaguchi K, Kaizawa H, Koizumi T, Ohishi T, Yamano M, Okada M, Ohta M, Tsukamoto S, Raynaud FI et al.. (2007)
Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors.
Bioorg Med Chem, 15 (17): 5837-44. [PMID:17601739]
7. Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O, Loewith R, Stokoe D, Balla A, Toth B et al.. (2006)
A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling.
Cell, 125 (4): 733-47. [PMID:16647110]
8. Raynaud FI, Eccles SA, Patel S, Alix S, Box G, Chuckowree I, Folkes A, Gowan S, De Haven Brandon A, Di Stefano F et al.. (2009)
Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941.
Mol Cancer Ther, 8 (7): 1725-38. [PMID:19584227]
9. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]