PIP2   Click here for help

GtoPdb Ligand ID: 2387

Synonyms: phosphatidylinositol-4,5-bisphosphate | PIP2
Compound class: Metabolite
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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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Click here for structure editor
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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 19
Hydrogen bond donors 8
Rotatable bonds 44
Topological polar surface area 332
Molecular weight 1022.49
XLogP 9.87
No. Lipinski's rules broken 4

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COP(=O)(OC1C(O)C(O)C(C(C1O)OP(=O)(O)O)OP(=O)(O)O)O
Isomeric SMILES CCCCCCCC/C=C\CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC/C=C\CCCCCCCC)COP(=O)(O[C@@H]1[C@H](O)[C@H](O)[C@H]([C@@H]([C@H]1O)OP(=O)(O)O)OP(=O)(O)O)O
InChI InChI=1S/C45H85O19P3/c1-3-5-7-9-11-13-15-17-19-21-23-25-27-29-31-33-38(46)59-35-37(61-39(47)34-32-30-28-26-24-22-20-18-16-14-12-10-8-6-4-2)36-60-67(57,58)64-43-40(48)41(49)44(62-65(51,52)53)45(42(43)50)63-66(54,55)56/h17-20,37,40-45,48-50H,3-16,21-36H2,1-2H3,(H,57,58)(H2,51,52,53)(H2,54,55,56)/b19-17-,20-18-/t37-,40-,41+,42+,43-,44-,45-/m1/s1
InChI Key IGQSAMXNWMLOOS-GGDMTQDZSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Baukrowitz T, Schulte U, Oliver D, Herlitze S, Krauter T, Tucker SJ, Ruppersberg JP, Fakler B. (1998)
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
Science, 282 (5391): 1141-4. [PMID:9804555]
2. Hammond SM, Jenco JM, Nakashima S, Cadwallader K, Gu Q, Cook S, Nozawa Y, Prestwich GD, Frohman MA, Morris AJ. (1997)
Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTP-binding proteins and protein kinase C-alpha.
J Biol Chem, 272 (6): 3860-8. [PMID:9013646]
3. Hilgemann DW, Ball R. (1996)
Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
Science, 273 (5277): 956-9. [PMID:8688080]
4. Huang CL, Feng S, Hilgemann DW. (1998)
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
Nature, 391 (6669): 803-6. [PMID:9486652]
5. Li Y, Gamper N, Hilgemann DW, Shapiro MS. (2005)
Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate.
J Neurosci, 25 (43): 9825-35. [PMID:16251430]
6. Lopez I, Arnold RS, Lambeth JD. (1998)
Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2.
J Biol Chem, 273 (21): 12846-52. [PMID:9582313]
7. Luo JQ, Liu X, Hammond SM, Colley WC, Feig LA, Frohman MA, Morris AJ, Foster DA. (1997)
RalA interacts directly with the Arf-responsive, PIP2-dependent phospholipase D1.
Biochem Biophys Res Commun, 235 (3): 854-9. [PMID:9207251]
8. Nilius B, Mahieu F, Prenen J, Janssens A, Owsianik G, Vennekens R, Voets T. (2006)
The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate.
EMBO J, 25 (3): 467-78. [PMID:16424899]
9. Pian P, Bucchi A, Robinson RB, Siegelbaum SA. (2006)
Regulation of gating and rundown of HCN hyperpolarization-activated channels by exogenous and endogenous PIP2.
J Gen Physiol, 128 (5): 593-604. [PMID:17074978]
10. Rapedius M, Soom M, Shumilina E, Schulze D, Schönherr R, Kirsch C, Lang F, Tucker SJ, Baukrowitz T. (2005)
Long chain CoA esters as competitive antagonists of phosphatidylinositol 4,5-bisphosphate activation in Kir channels.
J Biol Chem, 280 (35): 30760-7. [PMID:15980413]
11. Runnels LW, Yue L, Clapham DE. (2002)
The TRPM7 channel is inactivated by PIP(2) hydrolysis.
Nat Cell Biol, 4 (5): 329-36. [PMID:11941371]
12. Soom M, Schönherr R, Kubo Y, Kirsch C, Klinger R, Heinemann SH. (2001)
Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels.
FEBS Lett, 490 (1-2): 49-53. [PMID:11172809]
13. Tóth B, Csanády L. (2012)
Pore collapse underlies irreversible inactivation of TRPM2 cation channel currents.
Proc Natl Acad Sci USA, 109 (33): 13440-5. [PMID:22847436]
14. Zhang Z, Okawa H, Wang Y, Liman ER. (2005)
Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization.
J Biol Chem, 280 (47): 39185-92. [PMID:16186107]