iPPI-DB

Inhibitors of Protein-Protein Interaction Database


  • Number of compounds
  • Total number of binding data
  • Total number of biochemical binding data
  • 1756
  • 2591
  • 1999
  • Total number of cellular binding data
  • Number of proteins
  • Number of families
  • 592
  • 48
  • 18
  • Number of PPI targets
  • Number of bibliographic sources
  • 36
  • 128

What are the iPPI-DB standards ?

Here is some guidance to submit binding data that comply with iPPI-DB standards :

  • The PPI target must have a known functional mechanism
  • No peptide will be considered
  • Only dose response-based measures of activity are considered (e.g IC50, EC50, Kd, Ki)
  • Only activities below 30 μM will qualify the corresponding compounds


Binding data available in iPPI-DB

histogramme_family
Figure's caption:  Top left panel, distribution of the binding data across bins of activity in pXC50 units (i.e any of the following: pKi, pKd, pIC50, pEC50). Top right panel, amount of binding data per type of biochemical assay. Bottom left, number of compounds and binding data available in iPPI-DB per PPI target. Bottom right, amount of binding data per type of cellular assay.

Efficiencies: iPPI-DB biplot LE versus LLE

LLE

8

6

4

2

0

-2

-4

Efficiencies

0.2

0.3

0.4

0.5

LE


PPI's families

 

 BCL2-Like / BAX


 

 β-catenin / TCF-4


 

 BRD / H4


 

 CD4 / gp120


 

 CD80 / CD28


 

 E2 / E1


 

 FAK / VEGFR3


 

 IL2 / IL2R


 

 LEDGF / IN


 

 LFA / ICAM


 

 MDM2-Like / P53


 

 MENIN / MLL


 

 Myc / Max


 

 NRP / VEGF


 

 UPAR / UPA


 

 VEGF / VEGFR


 

 XIAP / Smac


 

 ZipA / ftsZ

Left panel: iPPI-DB biplot of Ligand Efficiency (LE = 1.37 x pXC50 / No heavy atoms) versus Lipophilic Ligand Efficiency (LLE = pXC50 - AlogP) where pXC50 is any of the following: pKd, pKi, pIC50 or pEC50. Each iPPI is colored according to their corresponding target.

Physicochemical profile of the 1756 compounds of iPPI-DB

histogramme_family
histogramme_family
Figure's caption:  Top panel, histograms of some commonly used molecular descriptors. Bottom panel, proportions of accepted and rejected iPPI-DB compounds with regards to widely used chemistry rules. Lipinski's RO5 corresponds to usually observed orally bioavailable drugs and tolerates one violation to (logP ≤ 5, MW ≤ 500g/mol, No H-Bond Acceptors ≤ 10 and No H-Bond Donors ≤ 5). Veber's rule corresponds to compounds that are orally bioavailable in rats (PSA ≤ 140Å2 and No Rotatable bonds ≤ 10). Finally, Pfizer's 3/75 rule states that there is a 6-fold reduction in toxicity in vivo (24-fold for bases) when logP ≤ 3 and PSA ≥ 75Å2.

PCA : iPPI-DB chemical space

Dim2 = 28.60 %

6

4

2

0

-2

-4

PCA

-5

0

5

Dim1 = 45.63 %


PPI's families

 

 BCL2-Like / BAX


 

 β-catenin / TCF-4


 

 BRD / H4


 

 CD4 / gp120


 

 CD80 / CD28


 

 E2 / E1


 

 FAK / VEGFR3


 

 IL2 / IL2R


 

 LEDGF / IN


 

 LFA / ICAM


 

 MDM2-Like / P53


 

 MENIN / MLL


 

 Myc / Max


 

 NRP / VEGF


 

 UPAR / UPA


 

 VEGF / VEGFR


 

 XIAP / Smac


 

 ZipA / ftsZ

PCA's correlation circle

coming soon

Left panel: individual map of the Principal Component Analysis (PCA) calculated on the iPPI-DB compounds. Each compound is colored to their corresponding target. Right Panel: variable map of the Principal Component Analysis calculated on the iPPI-DB compounds using 18 descriptors frequently used to depict chemical space.

iPPI-DB compounds in clinical trials

Amount of iPPI-DB compounds, that were in 2015, in preclinical trials or clinical trials per PPI target (according to data present in MDDR march 2015).