phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma | Phosphatidylinositol-4,5-bisphosphate 3-kinase family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma

  Target has curated data in GtoImmuPdb

Target id: 2156

Nomenclature: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma

Abbreviated Name: PI3Kγ

Family: Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1102 7q22 PIK3CG phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
Mouse - 1102 12 B Pik3cg phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
Rat - 1102 6 q16 Pik3cg phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma
Previous and Unofficial Names
p120-PI3K | PI3Kgamma | p110γ/PIK3CG | phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma | phosphatidylinositol-4
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
PDB Id:  1E8Y
Resolution:  2.0Å
Species:  Human
References:  61
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PI3Kγ) in complex with the dual PI3K/mTOR inhibitor PF-04691502.
PDB Id:  3ML9
Ligand:  PF-04691502
Resolution:  2.55Å
Species:  Human
References:  13
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human PI3K-gamma in complex with (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine AMG319 inhibitor.
Ligand:  AMG319
Resolution:  2.7Å
Species:  Human
References:  16
Enzyme Reaction
EC Number:

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
IPI549 Hs Inhibition 9.5 pKd 20
pKd 9.5 (Kd 2.9x10-10 M) [20]
AZ2 Hs Inhibition 8.6 pKd 25
pKd 8.6 (Kd 2.24x10-9 M) [25]
Description: Binding affinity determined by SPR using a two-step binding model.
neolymphostin A Hs Inhibition 8.5 pKd 12
pKd 8.5 (Kd 3.5x10-9 M) [12]
Description: Determined using an active-site dependent competition binding assay.
wortmannin Hs Inhibition 7.8 pKd 12
pKd 7.8 (Kd 1.5x10-8 M) [12]
CZC 24832 Hs Inhibition 7.7 pKd 7
pKd 7.7 [7]
bimiralisib Hs Inhibition 7.6 pKd
pKd 7.6 (Kd 2.5x10-8 M)
taselisib Hs Inhibition 8.8 – 9.0 pKi 8,47
pKi 9.0 (Ki 9.7x10-10 M) [47]
pKi 8.8 (Ki 1.43x10-9 M) [8]
compound 22 [PMID: 24754609] Hs Inhibition 8.7 pKi 15
pKi 8.7 (Ki 2x10-9 M) [15]
GDC-0077 Hs Inhibition 7.7 pKi 8
pKi 7.7 (Ki 1.82x10-8 M) [8]
omipalisib Hs Inhibition 7.6 pKi 35
pKi 7.6 (Ki 2.4x10-8 M) [35]
pictilisib Hs Inhibition 7.4 pKi 8
pKi 7.4 (Ki 4.18x10-8 M) [8]
berzosertib Hs Inhibition 6.7 pKi 21
pKi 6.7 (Ki 2.2x10-7 M) [21]
AZ2 Hs Inhibition 9.5 pIC50 25
pIC50 9.5 (IC50 3.5x10-10 M) [25]
Description: Biochemical assay using purified protein expressed from a construct containing C-terminal 6-His-tagged human p110&gamma (S144-A1102).
compound 15 [PMID: 29852070] Hs Inhibition 9.1 pIC50 51
pIC50 9.1 (IC50 7.9x10-10 M) [51]
Description: In a biochemical enzyme activity assay.
compound 15a [PMID: 32069401] Hs Inhibition 8.9 pIC50 68
pIC50 8.9 (IC50 1.2x10-9 M) [68]
compound 5d [PMID: 31335136] Hs Inhibition 8.8 pIC50 39
pIC50 8.8 (IC50 1.6x10-9 M) [39]
compound 82 [PMID: 21332118] Hs Inhibition 8.3 pIC50 17
pIC50 8.3 (IC50 4.7x10-9 M) [17]
dactolisib Hs Inhibition 8.3 pIC50 43
pIC50 8.3 (IC50 5x10-9 M) [43]
copanlisib Hs Inhibition 8.2 pIC50 41
pIC50 8.2 (IC50 6.4x10-9 M) [41]
PI 3-Kg inhibitor Hs Inhibition 8.1 pIC50 10
pIC50 8.1 (IC50 8x10-9 M) [10]
apitolisib Hs Inhibition 7.8 pIC50 57
pIC50 7.8 (IC50 1.4x10-8 M) [57]
PI-103 Hs Inhibition 7.8 pIC50 54
pIC50 7.8 (IC50 1.5x10-8 M) [54]
pilaralisib Hs Inhibition 7.6 pIC50 64
pIC50 7.6 (IC50 2.3x10-8 M) [64]
samotolisib Hs Inhibition 7.6 pIC50 5
pIC50 7.6 (IC50 2.38x10-8 M) [5]
tenalisib Hs Inhibition 7.6 pIC50 60
pIC50 7.6 (IC50 2.385x10-8 M) [60]
Description: In a high throughput biochemical assay.
VS-5584 Hs Inhibition 7.6 pIC50 29
pIC50 7.6 (IC50 2.5x10-8 M) [29]
RV1729 Hs Inhibition 7.6 pIC50 34
pIC50 7.6 (IC50 2.5x10-8 M) [34]
Description: In a biochemical enzyme activity assay.
CZC 24832 Hs Inhibition 7.6 pIC50 7
pIC50 7.6 (IC50 2.7x10-8 M) [7]
duvelisib Hs Inhibition 7.6 pIC50 62
pIC50 7.6 (IC50 2.7x10-8 M) [62]
RV6153 Hs Inhibition 7.6 pIC50 58
pIC50 7.6 (IC50 2.8x10-8 M) [58]
Description: In a biochemical enzyme activity assay.
AS-252424 Hs Inhibition 7.5 pIC50 52
pIC50 7.5 (IC50 3.3x10-8 M) [52]
MEN1611 Hs Inhibition 7.4 pIC50 49
pIC50 7.4 (IC50 3.6x10-8 M) [49]
BGT-226 Hs Inhibition 7.4 pIC50 44
pIC50 7.4 (IC50 3.8x10-8 M) [44]
ZSTK474 Hs Inhibition 7.3 – 7.3 pIC50 64,66
pIC50 7.3 – 7.3 (IC50 5.3x10-8 – 4.9x10-8 M) [64,66]
AZD7648 Hs Inhibition 7.3 pIC50 26
pIC50 7.3 (IC50 5.2x10-8 M) [26]
PIK-75 Hs Inhibition 7.1 – 7.4 pIC50 30,36
pIC50 7.4 (IC50 4x10-8 M) [30]
pIC50 7.1 (IC50 7.6x10-8 M) [36]
compound 11j [PMID: 23021994] Hs Inhibition 7.2 pIC50 27
pIC50 7.2 (IC50 6x10-8 M) [27]
pictilisib Hs Inhibition 7.1 pIC50 22
pIC50 7.1 (IC50 7.5x10-8 M) [22]
TG-100-115 Hs Inhibition 7.1 pIC50 50
pIC50 7.1 (IC50 8.3x10-8 M) [50]
idelalisib Hs Inhibition 7.1 pIC50 37
pIC50 7.1 (IC50 8.9x10-8 M) [37]
AZD8835 Hs Inhibition 7.1 pIC50 6
pIC50 7.1 (IC50 9x10-8 M) [6]
puquitinib Hs Inhibition 7.1 pIC50 65
pIC50 7.1 (IC50 8.98x10-8 M) [65]
compound 52 [PMID: 28541707] Hs Inhibition 6.8 pIC50 42
pIC50 6.8 (IC50 1.7x10-7 M) [42]
Description: Calculated based on potency being 100-fold lower for PI3Kγ than for PI3Kδ.
panulisib Hs Inhibition 6.7 pIC50 33
pIC50 6.7 (IC50 2.03x10-7 M) [33]
Description: Using a radiometric protein kinase (33PanQinase activity) assay.
sapanisertib Hs Inhibition 6.7 pIC50 32
pIC50 6.7 (IC50 2.21x10-7 M) [32]
PI 3-Kg inhibitor II Hs Inhibition 6.6 pIC50 10
pIC50 6.6 (IC50 2.5x10-7 M) [10]
alpelisib Hs Inhibition 6.6 pIC50 24
pIC50 6.6 (IC50 2.5x10-7 M) [24]
seletalisib Hs Inhibition 6.6 pIC50 3
pIC50 6.6 (IC50 2.82x10-7 M) [3]
fimepinostat Hs Inhibition 6.5 pIC50 53
pIC50 6.5 (IC50 3.11x10-7 M) [53]
compound 41 [PMID: 31855425] Hs Inhibition 6.5 pIC50 31
pIC50 6.5 (IC50 3.16x10-7 M) [31]
dezapelisib Hs Inhibition <6.3 pIC50 38
pIC50 <6.3 (IC50 >5x10-7 M) [38]
Example 51 [WO2012135160A1] Hs Inhibition <6.3 pIC50 9
pIC50 <6.3 (IC50 >5x10-7 M) [9]
KU-0060648 Hs Inhibition 6.2 pIC50 11
pIC50 6.2 (IC50 5.9x10-7 M) [11]
AZD8186 Hs Inhibition 6.2 pIC50 28
pIC50 6.2 (IC50 6.75x10-7 M) [28]
AMG319 Hs Inhibition 6.1 pIC50 16
pIC50 6.1 (IC50 8.5x10-7 M) [16]
STK16-IN-1 Hs Inhibition 6.1 pIC50 40
pIC50 6.1 (IC50 8.67x10-7 M) [40]
Description: In an in vitro enzymatic assay.
PP121 Hs Inhibition 6.0 pIC50 4
pIC50 6.0 (IC50 1.1x10-6 M) [4]
AZD6482 Hs Inhibition 6.0 pIC50 48
pIC50 6.0 (IC50 1.09x10-6 M) [48]
eCF309 Hs Inhibition 5.9 pIC50 23
pIC50 5.9 (IC50 1.34x10-6 M) [23]
Description: In a biochemical assay.
acalisib Hs Inhibition 5.9 pIC50 56
pIC50 5.9 (IC50 1.389x10-6 M) [56]
Description: In an in vitro biochemical assay using recombinant enzyme.
LY 294002 Hs Inhibition 5.5 – 5.9 pIC50 11,14
pIC50 5.5 – 5.9 (IC50 3.002x10-6 – 1.2x10-6 M) [11,14]
compound 2q [PMID: 30986068] Hs Inhibition 5.4 pIC50 45
pIC50 5.4 (IC50 3.783x10-6 M) [45]
Description: In a biochemical HTRF assay measuring generation of PIP3 via phosphorylation of PIP2, using PI3Kγ 14-558 fragment.
nemiralisib Hs Inhibition 5.2 pIC50 19
pIC50 5.2 (IC50 6.31x10-6 M) [19]
Description: In a homogeneous time-resolved fluorescence (HTRF) assay
serabelisib Hs Inhibition >5.0 pIC50 55
pIC50 >5.0 (IC50 <1x10-5 M) [55]
quinostatin Hs Inhibition 4.5 pIC50 67
pIC50 4.5 (IC50 3x10-5 M) [67]
Description: Inhibition of lipid-kinase activity in vitro.
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 18,63

Key to terms and symbols Click column headers to sort
Target used in screen: PIK3CG
Ligand Sp. Type Action Value Parameter
TG-100-115 Hs Inhibitor Inhibition 8.3 pKd
PI-103 Hs Inhibitor Inhibition 7.8 pKd
PP-242 Hs Inhibitor Inhibition 7.4 pKd
pictilisib Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Hs Inhibitor Inhibition 6.5 pKd
staurosporine Hs Inhibitor Inhibition 5.7 pKd
GSK-461364A Hs Inhibitor Inhibition 5.7 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Hs Inhibitor Inhibition <5.5 pKd
erlotinib Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
The role of PI3Kγ in immuno-oncology is reviewed in [1]. A detailed analysis of the function of PI3Kγ in malignant B cells indicated that it is crucial for chemokine gradient sensing and adhesion to stromal cells (i.e. malignant B cell migration) [2].

The PI3Kγ isoform is of particular therapeutic interest in chronic obstructive airway diseases, such as severe asthma and COPD. This Class IB PI3K isoform has regulatory roles in mediating neutrophil migration (in response to asthmatic epithelial conditioned medium [59]) and degranulation that may contribute to inflammation-mediated tissue damage of the airways [46].
Immuno Process Associations
Immuno Process:  Inflammation
Comment:  Neutrophil degranulation (GO:0043312) [46,59].
GO Annotations:  Associated to 9 GO processes
GO:0002407 dendritic cell chemotaxis TAS
GO:0006954 inflammatory response TAS
GO:0010818 T cell chemotaxis TAS
GO:0030593 neutrophil chemotaxis TAS
GO:0035747 natural killer cell chemotaxis TAS
GO:0043303 mast cell degranulation TAS
GO:0045087 innate immune response TAS
GO:0072672 neutrophil extravasation TAS
click arrow to show/hide IEA associations
GO:0002675 positive regulation of acute inflammatory response IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 3 GO processes
GO:0002250 adaptive immune response TAS
GO:0042098 T cell proliferation TAS
GO:0042110 T cell activation TAS
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002250 adaptive immune response TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0001816 cytokine production TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 5 GO processes
GO:0002407 dendritic cell chemotaxis TAS
GO:0010818 T cell chemotaxis TAS
GO:0030593 neutrophil chemotaxis TAS
GO:0035747 natural killer cell chemotaxis TAS
GO:0072672 neutrophil extravasation TAS
Immuno Process:  Cellular signalling
Comment:  Neutrophil degranulation (GO:0043312) [46,59].
GO Annotations:  Associated to 3 GO processes
GO:0042098 T cell proliferation TAS
GO:0042110 T cell activation TAS
GO:0043303 mast cell degranulation TAS
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0006897 endocytosis IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002675 positive regulation of acute inflammatory response IEA


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23. Fraser C, Carragher NO, Unciti-Broceta A. (2016) eCF309: a potent, selective and cell-permeable mTOR inhibitor. Medchemcomm, 7 (3): 471-477.

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