Details of the Drug

General Information of Drug (ID: DMOZV7N)

Drug Name
PIP2
Synonyms phosphatidylinositol-4,5-bisphosphate
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 5 Molecular Weight (mw) 1023.1
Topological Polar Surface Area (xlogp) 8.3
Rotatable Bond Count (rotbonds) 44
Hydrogen Bond Donor Count (hbonddonor) 8
Hydrogen Bond Acceptor Count (hbondacc) 19
Chemical Identifiers
Formula
C45H85O19P3
IUPAC Name
[(2R)-3-[hydroxy-[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-diphosphonooxycyclohexyl]oxyphosphoryl]oxy-2-[(Z)-octadec-9-enoyl]oxypropyl] (Z)-octadec-9-enoate
Canonical SMILES
CCCCCCCC/C=C\\CCCCCCCC(=O)OC[C@H](COP(=O)(O)O[C@@H]1[C@@H]([C@@H]([C@H]([C@@H]([C@H]1O)OP(=O)(O)O)OP(=O)(O)O)O)O)OC(=O)CCCCCCC/C=C\\CCCCCCCC
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
InChIKey
IGQSAMXNWMLOOS-GGDMTQDZSA-N
Cross-matching ID
PubChem CID
5311358
TTD ID
D07ZAJ
VARIDT ID
DR01018

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Hyperpolarization cyclic nucleotide-gated channel 2 (HCN2) TT9EUT4 HCN2_HUMAN Activator [2]
Inward rectifier potassium channel Kir2.1 (KCNJ2) TTH7UO3 KCNJ2_HUMAN Activator [3]
Inward rectifier potassium channel Kir3.1 (KCNJ3) TTGM19J KCNJ3_HUMAN Activator [4]
Inward rectifier potassium channel Kir3.2 (KCNJ6) TTTIBVP KCNJ6_HUMAN Activator [4]
Inward rectifier potassium channel Kir3.3 (KCNJ9) TT4VHL6 KCNJ9_HUMAN Activator [5]
Inward rectifier potassium channel Kir3.4 (KCNJ5) TTEO25X KCNJ5_HUMAN Activator [6]
IP3 receptor isoform 1 (ITPR1) TT5HWAT ITPR1_HUMAN Antagonist [7]
Long transient receptor potential channel 4 (TRPM4) TTJ2HKA TRPM4_HUMAN Activator [8]
Long transient receptor potential channel 7 (TRPM7) TTFPVZO TRPM7_HUMAN Activator [9]
Phospholipase D2 (PLD2) TTRLMKF PLD2_HUMAN Activator [10]
Voltage-gated potassium channel Kv7.2 (KCNQ2) TTPXI3S KCNQ2_HUMAN Activator [11]
Voltage-gated potassium channel Kv7.4 (KCNQ4) TT8HGRW KCNQ4_HUMAN Activator [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2387).
2 Regulation of gating and rundown of HCN hyperpolarization-activated channels by exogenous and endogenous PIP2. J Gen Physiol. 2006 Nov;128(5):593-604.
3 Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels. FEBS Lett. 2001 Feb 9;490(1-2):49-53.
4 Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma. Nature. 1998 Feb 19;391(6669):803-6.
5 Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2. Science. 1996 Aug 16;273(5277):956-9.
6 PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science. 1998 Nov 6;282(5391):1141-4.
7 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 743).
8 Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization. J Biol Chem. 2005 Nov 25;280(47):39185-92.
9 The TRPM7 channel is inactivated by PIP(2) hydrolysis. Nat Cell Biol. 2002 May;4(5):329-36.
10 Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2. J Biol Chem. 1998 May 22;273(21):12846-52.
11 Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J Neurosci. 2005 Oct 26;25(43):9825-35.
12 Design, synthesis, and biological evaluation of halogenated N-(2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: discovery of an isoform-selective small molecule phospholipase D2 inhibitor. J Med Chem. 2010 Sep 23;53(18):6706-19.
13 LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature. 2001 May 31;411(6837):590-5.
14 Carvacrol is a novel inhibitor of Drosophila TRPL and mammalian TRPM7 channels. Cell Calcium. 2009 Mar;45(3):300-9.
15 Waixenicin A inhibits cell proliferation through magnesium-dependent block of transient receptor potential melastatin 7 (TRPM7) channels. J Biol Chem. 2011 Nov 11;286(45):39328-35.
16 Differential effects of general anesthetics on G protein-coupled inwardly rectifying and other potassium channels. Anesthesiology. 2001 Jul;95(1):144-53.
17 ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice. ACS Chem Neurosci. 2013 Sep 18;4(9):1278-86.
18 Homomeric and heteromeric assembly of KCNQ (Kv7) K+ channels assayed by total internal reflection fluorescence/fluorescence resonance energy transfer and patch clamp analysis. J Biol Chem. 2008 Nov 7;283(45):30668-76.
19 Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol. 2007 May;3(5):287-96.
20 KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology. Am J Physiol Cell Physiol. 2001 Apr;280(4):C859-66.
21 The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology. 2006 Nov;51(6):1068-77.
22 Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay. Anal Biochem. 2011 Nov 1;418(1):66-72.
23 Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener. ACS Chem Neurosci. 2011 Oct 19;2(10):572-577.
24 Regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity by cCMP. J Biol Chem. 2012 Aug 3;287(32):26506-12.
25 Voltage-gated Potassium Channels as Therapeutic Drug Targets
26 Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600.
27 Synthesis and biological activity of substituted bis-(4-hydroxyphenyl)methanes as N-type calcium channel blockers. Bioorg Med Chem Lett. 1999 Aug 16;9(16):2447-52.
28 KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science. 1998 Dec 4;282(5395):1890-3.
29 Modulation of K(v)7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58. Br J Pharmacol. 2013 Feb;168(4):1030-42.
30 The KCNQ2/3 selective channel opener ICA-27243 binds to a novel voltage-sensor domain site. Neurosci Lett. 2009 Nov 13;465(2):138-42.
31 Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions. J Biol Chem. 2010 Sep 3;285(36):28322-32.
32 Cytoplasmic accumulation of long-chain coenzyme A esters activates KATP and inhibits Kir2.1 channels. J Physiol. 2006 Sep 1;575(Pt 2):433-42.
33 Molecular basis for the inhibition of G protein-coupled inward rectifier K(+) channels by protein kinase C. Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):1087-92.
34 Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b. Pflugers Arch. 2004 Apr;448(1):70-5.
35 Decavanadate modulates gating of TRPM4 cation channels. J Physiol. 2004 Nov 1;560(Pt 3):753-65.
36 A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 ch... Mol Pharmacol. 2006 Apr;69(4):1413-20.
37 9-phenanthrol inhibits human TRPM4 but not TRPM5 cationic channels. Br J Pharmacol. 2008 Apr;153(8):1697-705.