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

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Immunopharmacology Ligand 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

Gene and Protein Information Click here for help
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 Click here for help
p120-PI3K | PI3Kgamma | p110γ/PIK3CG | phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma | phosphatidylinositol-4
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  STRUCTURE DETERMINANTS OF PHOSPHOINOSITIDE 3-KINASE INHIBITION BY WORTMANNIN, LY294002, QUERCETIN, MYRICETIN AND STAUROSPORINE
PDB Id:  1E8Y
Resolution:  2.0Å
Species:  Human
References:  62
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.
PDB Id:  4WWN
Ligand:  AMG319
Resolution:  2.7Å
Species:  Human
References:  16
Enzyme Reaction Click here for help
EC Number: 2.7.1.153

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
IPI549 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.5 pKd 20
pKd 9.5 (Kd 2.9x10-10 M) [20]
AZ2 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand 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 Small molecule or natural product Click here for species-specific activity table 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 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pKd 12
pKd 7.8 (Kd 1.5x10-8 M) [12]
CZC 24832 Small molecule or natural product Primary target of this compound Hs Inhibition 7.7 pKd 7
pKd 7.7 [7]
bimiralisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pKd
pKd 7.6 (Kd 2.5x10-8 M)
taselisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure 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] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pKi 15
pKi 8.7 (Ki 2x10-9 M) [15]
GDC-0077 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pKi 8
pKi 7.7 (Ki 1.82x10-8 M) [8]
omipalisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.6 pKi 35
pKi 7.6 (Ki 2.4x10-8 M) [35]
pictilisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKi 8
pKi 7.4 (Ki 4.18x10-8 M) [8]
berzosertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pKi 21
pKi 6.7 (Ki 2.2x10-7 M) [21]
AZ2 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand 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] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 51
pIC50 9.1 (IC50 7.9x10-10 M) [51]
Description: In a biochemical enzyme activity assay.
AZD8154 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 52
pIC50 9.1 (IC50 9x10-10 M) [52]
compound 15a [PMID: 32069401] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.9 pIC50 69
pIC50 8.9 (IC50 1.2x10-9 M) [69]
compound 5d [PMID: 31335136] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.8 pIC50 39
pIC50 8.8 (IC50 1.6x10-9 M) [39]
compound 82 [PMID: 21332118] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 17
pIC50 8.3 (IC50 4.7x10-9 M) [17]
dactolisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pIC50 43
pIC50 8.3 (IC50 5x10-9 M) [43]
copanlisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 41
pIC50 8.2 (IC50 6.4x10-9 M) [41]
PI 3-Kg inhibitor Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 10
pIC50 8.1 (IC50 8x10-9 M) [10]
apitolisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 58
pIC50 7.8 (IC50 1.4x10-8 M) [58]
PI-103 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 55
pIC50 7.8 (IC50 1.5x10-8 M) [55]
pilaralisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 65
pIC50 7.6 (IC50 2.3x10-8 M) [65]
samotolisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 5
pIC50 7.6 (IC50 2.38x10-8 M) [5]
tenalisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.6 pIC50 61
pIC50 7.6 (IC50 2.385x10-8 M) [61]
Description: In a high throughput biochemical assay.
VS-5584 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.6 pIC50 29
pIC50 7.6 (IC50 2.5x10-8 M) [29]
RV1729 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.6 pIC50 34
pIC50 7.6 (IC50 2.5x10-8 M) [34]
Description: In a biochemical enzyme activity assay.
CZC 24832 Small molecule or natural product Primary target of this compound Hs Inhibition 7.6 pIC50 7
pIC50 7.6 (IC50 2.7x10-8 M) [7]
duvelisib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.6 pIC50 63
pIC50 7.6 (IC50 2.7x10-8 M) [63]
RV6153 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.6 pIC50 59
pIC50 7.6 (IC50 2.8x10-8 M) [59]
Description: In a biochemical enzyme activity assay.
AS-252424 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 53
pIC50 7.5 (IC50 3.3x10-8 M) [53]
MEN1611 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 49
pIC50 7.4 (IC50 3.6x10-8 M) [49]
BGT-226 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.4 pIC50 44
pIC50 7.4 (IC50 3.8x10-8 M) [44]
ZSTK474 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 – 7.3 pIC50 65,67
pIC50 7.3 – 7.3 (IC50 5.3x10-8 – 4.9x10-8 M) [65,67]
AZD7648 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 26
pIC50 7.3 (IC50 5.2x10-8 M) [26]
PIK-75 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure 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] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 27
pIC50 7.2 (IC50 6x10-8 M) [27]
pictilisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 22
pIC50 7.1 (IC50 7.5x10-8 M) [22]
TG-100-115 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 50
pIC50 7.1 (IC50 8.3x10-8 M) [50]
idelalisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 37
pIC50 7.1 (IC50 8.9x10-8 M) [37]
AZD8835 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 6
pIC50 7.1 (IC50 9x10-8 M) [6]
puquitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 66
pIC50 7.1 (IC50 8.98x10-8 M) [66]
compound 52 [PMID: 28541707] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand 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 Small molecule or natural product Click here for species-specific activity table 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 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 pIC50 32
pIC50 6.7 (IC50 2.21x10-7 M) [32]
PI 3-Kg inhibitor II Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 10
pIC50 6.6 (IC50 2.5x10-7 M) [10]
alpelisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 24
pIC50 6.6 (IC50 2.5x10-7 M) [24]
seletalisib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 3
pIC50 6.6 (IC50 2.82x10-7 M) [3]
fimepinostat Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.5 pIC50 54
pIC50 6.5 (IC50 3.11x10-7 M) [54]
compound 41 [PMID: 31855425] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.5 pIC50 31
pIC50 6.5 (IC50 3.16x10-7 M) [31]
dezapelisib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition <6.3 pIC50 38
pIC50 <6.3 (IC50 >5x10-7 M) [38]
Example 51 [WO2012135160A1] Small molecule or natural product Click here for species-specific activity table Hs Inhibition <6.3 pIC50 9
pIC50 <6.3 (IC50 >5x10-7 M) [9]
KU-0060648 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 11
pIC50 6.2 (IC50 5.9x10-7 M) [11]
AZD8186 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 28
pIC50 6.2 (IC50 6.75x10-7 M) [28]
AMG319 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 16
pIC50 6.1 (IC50 8.5x10-7 M) [16]
STK16-IN-1 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 40
pIC50 6.1 (IC50 8.67x10-7 M) [40]
Description: In an in vitro enzymatic assay.
PP121 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 pIC50 4
pIC50 6.0 (IC50 1.1x10-6 M) [4]
AZD6482 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 pIC50 48
pIC50 6.0 (IC50 1.09x10-6 M) [48]
eCF309 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.9 pIC50 23
pIC50 5.9 (IC50 1.34x10-6 M) [23]
Description: In a biochemical assay.
acalisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.9 pIC50 57
pIC50 5.9 (IC50 1.389x10-6 M) [57]
Description: In an in vitro biochemical assay using recombinant enzyme.
LY 294002 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure 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] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand 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 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand 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 Small molecule or natural product Click here for species-specific activity table Hs Inhibition >5.0 pIC50 56
pIC50 >5.0 (IC50 <1x10-5 M) [56]
quinostatin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.5 pIC50 68
pIC50 4.5 (IC50 3x10-5 M) [68]
Description: Inhibition of lipid-kinase activity in vitro.
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 18,64

Key to terms and symbols Click column headers to sort
Target used in screen: PIK3CG
Ligand Sp. Type Action Value Parameter
TG-100-115 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
PI-103 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
pictilisib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.7 pKd
GSK-461364A Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure 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 [60]) 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) [46,60].
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) [46,60].
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

References

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1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov, 14 (9): 603-22. [PMID:26228631]

2. Ali AY, Wu X, Eissa N, Hou S, Ghia JE, Murooka TT, Banerji V, Johnston JB, Lin F, Gibson SB et al.. (2018) Distinct roles for phosphoinositide 3-kinases γ and δ in malignant B cell migration. Leukemia, 32 (9): 1958-1969. [PMID:29479062]

3. Allen RA, Brookings DC, Powell MJ, Delgado J, Shuttleworth LK, Merriman M, Fahy IJ, Tewari R, Silva JP, Healy LJ et al.. (2017) Seletalisib: Characterization of a Novel, Potent, and Selective Inhibitor of PI3Kδ. J. Pharmacol. Exp. Ther., 361 (3): 429-440. [PMID:28442583]

4. Apsel B, Blair JA, Gonzalez B, Nazif TM, Feldman ME, Aizenstein B, Hoffman R, Williams RL, Shokat KM, Knight ZA. (2008) Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat. Chem. Biol., 4 (11): 691-9. [PMID:18849971]

5. Barda DA, Mader MM. (2013) PI3 kinase/mTOR dual inhibitor. Patent number: US8440829 B2. Assignee: Eli Lilly And Company. Priority date: 14/01/2011. Publication date: 14/05/2013.

6. Barlaam B, Cosulich S, Delouvrié B, Ellston R, Fitzek M, Germain H, Green S, Hancox U, Harris CS, Hudson K et al.. (2015) Discovery of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (AZD8835): A potent and selective inhibitor of PI3Kα and PI3Kδ for the treatment of cancers. Bioorg. Med. Chem. Lett., 25 (22): 5155-62. [PMID:26475521]

7. Bergamini G, Bell K, Shimamura S, Werner T, Cansfield A, Müller K, Perrin J, Rau C, Ellard K, Hopf C et al.. (2012) A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation. Nat. Chem. Biol., 8 (6): 576-82. [PMID:22544264]

8. Braun M-G, Hanan E, Staben ST, Heald RA, Macleod C, Elliott R. (2017) Benzoxazepin oxazolidinone compounds and methods of use. Patent number: US20170015678. Assignee: Genentech, Inc.. Priority date: 02/07/2015. Publication date: 19/01/2017.

9. Brown SD, Matthews DJ. (2012) (alpha- substituted aralkylamino and heteroarylalkylamino) pyrimidinyl and 1,3,5 -triazinyl benzimidazoles, pharmaceutical compositions containing them, and these compounds for use in treating proliferative diseases. Patent number: WO2012135160A1. Assignee: Pathway Therapeutics Inc.. Priority date: 28/03/2011. Publication date: 04/10/2012.

10. Camps M, Rückle T, Ji H, Ardissone V, Rintelen F, Shaw J, Ferrandi C, Chabert C, Gillieron C, Françon B et al.. (2005) Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat. Med., 11 (9): 936-43. [PMID:16127437]

11. Cano C, Saravanan K, Bailey C, Bardos J, Curtin NJ, Frigerio M, Golding BT, Hardcastle IR, Hummersone MG, Menear KA et al.. (2013) 1-substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed with dual DNA-PK/PI3-K inhibitory activity. J. Med. Chem., 56 (16): 6386-401. [PMID:23855836]

12. Castro-Falcón G, Seiler GS, Demir Ö, Rathinaswamy MK, Hamelin D, Hoffmann RM, Makowski SL, Letzel AC, Field SJ, Burke JE et al.. (2018) Neolymphostin A Is a Covalent Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitor That Employs an Unusual Electrophilic Vinylogous Ester. J. Med. Chem., 61 (23): 10463-10472. [PMID:30380865]

13. Cheng H, Li C, Bailey S, Baxi SM, Goulet L, Guo L, Hoffman J, Jiang Y, Johnson TO, Johnson TW et al.. (2013) Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. ACS Med Chem Lett, 4 (1): 91-7. [PMID:24900568]

14. Cherian PT, Koikov LN, Wortman MD, Knittel JJ. (2009) Exploring the PI3K alpha and gamma binding sites with 2,6-disubstituted isonicotinic derivatives. Bioorg. Med. Chem. Lett., 19 (8): 2215-9. [PMID:19297156]

15. Collier PN, Martinez-Botella G, Cornebise M, Cottrell KM, Doran JD, Griffith JP, Mahajan S, Maltais F, Moody CS, Huck EP et al.. (2015) Structural basis for isoform selectivity in a class of benzothiazole inhibitors of phosphoinositide 3-kinase γ. J. Med. Chem., 58 (1): 517-21. [PMID:24754609]

16. Cushing TD, Hao X, Shin Y, Andrews K, Brown M, Cardozo M, Chen Y, Duquette J, Fisher B, Gonzalez-Lopez de Turiso F et al.. (2015) Discovery and in vivo evaluation of (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and related PI3Kδ inhibitors for inflammation and autoimmune disease. J. Med. Chem., 58 (1): 480-511. [PMID:25469863]

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