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

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2155

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

Abbreviated Name: PI3Kδ

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

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1044 1p36.22 PIK3CD phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta 83
Mouse - 1043 4 E2 Pik3cd phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
Rat - 944 5q36 Pik3cd phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta
Previous and Unofficial Names Click here for help
PI3Kdelta | p110δ/PIK3CD | phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta | phosphatidylinositol-4 | phosphatidylinositol 3-kinase catalytic delta polypeptide
Database Links Click here for help
Alphafold O00329 (Hs), O35904 (Mm)
BRENDA 2.7.1.153
CATH/Gene3D 2.60.40.150, 1.10.1070.11
ChEMBL Target CHEMBL3130 (Hs), CHEMBL2216745 (Mm)
Ensembl Gene ENSG00000171608 (Hs), ENSMUSG00000039936 (Mm), ENSRNOG00000016846 (Rn)
Entrez Gene 5293 (Hs), 18707 (Mm), 366508 (Rn)
Human Protein Atlas ENSG00000171608 (Hs)
KEGG Enzyme 2.7.1.153
KEGG Gene hsa:5293 (Hs), mmu:18707 (Mm), rno:366508 (Rn)
OMIM 602839 (Hs)
Pharos O00329 (Hs)
RefSeq Nucleotide NM_005026 (Hs), NM_001029837 (Mm), NM_001108978 (Rn)
RefSeq Protein NP_005017 (Hs), NP_001025008 (Mm), NP_001102448 (Rn)
UniProtKB O00329 (Hs), O35904 (Mm)
Wikipedia PIK3CD (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Discovery and Optimization of New Benzimidazole- and Benzoxazole-Pyrimidone Selective PI3KBeta Inhibitors for the Treatment of Phosphatase and TENsin homologue (PTEN)-Deficient Cancers
PDB Id:  4AJW
Resolution:  2.8Å
Species:  Mouse
References:  18
Image of receptor 3D structure from RCSB PDB
Description:  The crystal structure of the murine class IA PI 3-kinase p110delta in complex with IC-87114.
PDB Id:  2X38
Ligand:  IC-87114
Resolution:  2.2Å
Species:  Mouse
References:  9
Image of receptor 3D structure from RCSB PDB
Description:  PI3K delta in complex with 2methoxyN[2methoxy5(7{[(2R)4(oxetan3 yl)morpholin2yl]methoxy}1,3dihydro2 benzofuran5yl)pyridin3yl]ethane1 sulfonamide
PDB Id:  6TNS
Ligand:  compound 41 [PMID: 31855425]
Resolution:  2.4Å
Species:  Mouse
References:  39
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
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 9.7 pKd 39
⤷ pKd 9.7 (Kd 2x10-10 M) [39]
Description: Apparent binding affinity determined using the lipid kinobead assay.
neolymphostin A Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pKd 16
⤷ pKd 8.3 (Kd 4.9x10-9 M) [16]
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 8.3 pKd 16
⤷ pKd 8.3 (Kd 5.5x10-9 M) [16]
eganelisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.6 pKd 28
⤷ pKd 7.6 (Kd 2.3x10-8 M) [28]
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)
LY 294002 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pKd 25
⤷ pKd 6.2 (Kd 7.1x10-7 M) [25]
GSK2292767 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 10.1 pKi 8
⤷ pKi 10.1 (Ki 8x10-11 M) [8]
taselisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.7 – 10.1 pKi 12,62
⤷ pKi 10.1 (Ki 7.9x10-11 M) [12]
pKi 9.7 (Ki 2.1x10-10 M) [62]
PF-06843195 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >9.6 pKi 19
⤷ pKi >9.6 (Ki <2.8x10-10 M) [19]
CHF-6523 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.1 pKi 10
⤷ pKi 9.1 (Ki 9x10-10 M) [10]
compound 82 [PMID: 21332118] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pKi 23
⤷ pKi 8.9 (Ki 1.2x10-9 M) [23]
pictilisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.8 pKi 12
⤷ pKi 8.8 (Ki 1.54x10-9 M) [12]
inavolisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.9 pKi 12
⤷ pKi 7.9 (Ki 1.22x10-8 M) [12]
IC-87114 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition ~7.7 pKi 48
⤷ pKi ~7.7 (Ki ~2x10-8 M) [48]
omipalisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.2 pKi 46
⤷ pKi 7.2 (Ki 6x10-8 M) [46]
AZ2 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.7 pKi 35
⤷ pKi 6.7 (Ki 1.99x10-7 M) [35]
KU-0060648 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >10.0 pIC50 15
⤷ pIC50 >10.0 (IC50 <1x10-10 M) [15]
nemiralisib 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 9.9 pIC50 26
⤷ pIC50 9.9 (IC50 1.26x10-10 M) [26]
Description: In a homogeneous time-resolved fluorescence (HTRF) assay in the presence of 2mM ATP.
amdizalisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.5 pIC50 75
⤷ pIC50 9.5 (IC50 3x10-10 M) [75]
compound 15a [PMID: 32069401] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.3 pIC50 92
⤷ pIC50 9.3 (IC50 5x10-10 M) [92]
compound 20f [PMID: 28520415] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.2 pIC50 68
⤷ pIC50 9.2 (IC50 6.3x10-10 M) [68]
copanlisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 54
⤷ pIC50 9.1 (IC50 7x10-10 M) [54]
AZD8154 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 67
⤷ pIC50 9.1 (IC50 7x10-10 M) [67]
compound (S)-29 [PMID: 37606563] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 79
⤷ pIC50 9.1 (IC50 8x10-10 M) [79]
compound 5d [PMID: 31335136] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.0 pIC50 52
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [52]
compound 52 [PMID: 28541707] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.8 pIC50 55
⤷ pIC50 8.8 (IC50 1.7x10-9 M) [55]
CHF-6523 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.8 pIC50 10
⤷ pIC50 8.8 (IC50 1.7x10-9 M) [10]
bosmolisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 91
⤷ pIC50 8.7 (IC50 2x10-9 M) [91]
linperlisib Small molecule or natural product Primary target of this compound Hs Inhibition 8.6 pIC50 89
⤷ pIC50 8.6 (IC50 2.4x10-9 M) [89]
Description: Measured in a luminescence assay to detect modulation of ADP formation in the presence of test compound and hPI3Kδ.
idelalisib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.6 pIC50 49
⤷ pIC50 8.6 (IC50 2.5x10-9 M) in vitro activity against recombinant enzyme [49]
duvelisib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.6 pIC50 85
⤷ pIC50 8.6 (IC50 2.5x10-9 M) [85]
RV6153 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.6 pIC50 77
⤷ pIC50 8.6 (IC50 2.5x10-9 M) [77]
Description: In a biochemical enzyme activity assay.
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 8.5 pIC50 30
⤷ pIC50 8.5 (IC50 3x10-9 M) [30]
PI-103 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 71
⤷ pIC50 8.5 (IC50 3x10-9 M) [71]
puquitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 88
⤷ pIC50 8.5 (IC50 3.3x10-9 M) [88]
compound 2q [PMID: 30986068] 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 8.4 pIC50 60
⤷ pIC50 8.4 (IC50 3.9x10-9 M) [60]
Description: In a biochemical HTRF assay measuring generation of PIP3 via phosphorylation of PIP2, using PI3Kδ 14-604 fragment.
panulisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 43
⤷ pIC50 8.4 (IC50 4x10-9 M) [43]
Description: Using a radiometric protein kinase (33PanQinase activity) assay.
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 8.2 – 8.3 pIC50 87,90
⤷ pIC50 8.2 – 8.3 (IC50 6x10-9 – 5x10-9 M) [87,90]
torin 2 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 56
⤷ pIC50 8.3 (IC50 5.67x10-9 M) [56]
AZD8835 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.2 pIC50 7
⤷ pIC50 8.2 (IC50 5.7x10-9 M) [7]
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 8.2 pIC50 39
⤷ pIC50 8.2 (IC50 6.31x10-9 M) [39]
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 8.2 pIC50 76
⤷ pIC50 8.2 (IC50 6.7x10-9 M) [76]
dactolisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 59
⤷ pIC50 8.1 (IC50 7x10-9 M) [59]
AZD8186 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 36
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [36]
seletalisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 3
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [3]
RV1729 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 45
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [45]
Description: In a biochemical enzyme activity assay.
acalisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.9 pIC50 74
⤷ pIC50 7.9 (IC50 1.27x10-8 M) [74]
Description: In an in vitro biochemical assay using recombinant enzyme.
umbralisib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 82
⤷ pIC50 7.9 (IC50 1.383x10-8 M) [82]
PI-3065 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.8 pIC50 2
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [2]
AMG319 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 7.7 pIC50 22
⤷ pIC50 7.7 (IC50 1.8x10-8 M) [22]
parsaclisib Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.3 – 8.0 pIC50 51
⤷ pIC50 7.3 – 8.0 (IC50 5x10-8 – 1x10-8 M) [51]
leniolisib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.6 pIC50 20
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [20]
Description: In vitro enzyme assay
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 81
⤷ pIC50 7.6 (IC50 2.405x10-8 M) [81]
Description: In a high throughput biochemical assay.
pilaralisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 87
⤷ pIC50 7.4 (IC50 3.6x10-8 M) [87]
samotolisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 6
⤷ pIC50 7.4 (IC50 3.8x10-8 M) [6]
fimepinostat Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.4 pIC50 69
⤷ pIC50 7.4 (IC50 3.9x10-8 M) [69]
VS-5584 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.4 pIC50 38
⤷ pIC50 7.4 (IC50 4.2x10-8 M) [38]
vulolisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 93
⤷ pIC50 7.3 (IC50 4.9x10-8 M) [93]
dezapelisib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >7.3 pIC50 50
⤷ pIC50 >7.3 (IC50 <5x10-8 M) [50]
Description: The same value was obtained using an enzyme activity assay and a scintillation proximity assay.
XRD-0394 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 32
⤷ pIC50 7.1 (IC50 7.3x10-8 M) [32]
AZD6482 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 63
⤷ pIC50 7.1 (IC50 8x10-8 M) [63]
TGX-221 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 42
⤷ pIC50 7.0 (IC50 1x10-7 M) [42]
zandelisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >7.0 pIC50 13
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [13]
PP121 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 5
⤷ pIC50 6.8 (IC50 1.5x10-7 M) [5]
compound 27 [PMID: 35834807] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 40
⤷ pIC50 6.8 (IC50 1.53x10-7 M) [40]
LY 294002 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 pIC50 15
⤷ pIC50 6.7 (IC50 2.2x10-7 M) [15]
sapanisertib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Hs Inhibition 6.6 pIC50 41
⤷ pIC50 6.6 (IC50 2.3x10-7 M) [41]
NVP-CLR457 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 29
⤷ pIC50 6.6 (IC50 2.3x10-7 M) [29]
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 6.6 pIC50 65
⤷ pIC50 6.6 (IC50 2.35x10-7 M) [65]
DS-7423 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pIC50 44
⤷ pIC50 6.6 (IC50 2.6x10-7 M) [44]
alpelisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.5 pIC50 33
⤷ pIC50 6.5 (IC50 2.9x10-7 M) [33]
PI 3-Kg inhibitor Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.5 pIC50 14
⤷ pIC50 6.5 (IC50 3x10-7 M) [14]
AZD3458 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.5 pIC50 66
⤷ pIC50 6.5 (IC50 3.16x10-7 M) [66]
Description: In a biochemical enzyme activity assay.
SAR260301 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 17
⤷ pIC50 6.3 (IC50 4.68x10-7 M) [17]
izorlisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 64
⤷ pIC50 6.3 (IC50 5x10-7 M) [64]
IC-87114 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.3 pIC50 73
⤷ pIC50 6.3 (IC50 5x10-7 M) [73]
PIK-75 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 47
⤷ pIC50 6.3 (IC50 5.1x10-7 M) [47]
STK16-IN-1 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 53
⤷ pIC50 6.1 (IC50 8.56x10-7 M) [53]
Description: In an in vitro enzymatic assay.
compound 7 [PMID: 31955578] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.8 pIC50 11
⤷ pIC50 5.8 (IC50 1.7x10-6 M) [11]
eCF309 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.7 pIC50 31
⤷ pIC50 5.7 (IC50 1.84x10-6 M) [31]
Description: In a biochemical assay.
serabelisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition >5.0 pIC50 72
⤷ pIC50 >5.0 (IC50 <1x10-5 M) [72]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
roginolisib Small molecule or natural product Hs Inhibition 6.5 pIC50 34
⤷ pIC50 6.5 (IC50 3.47x10-7 M) [34]
Description: Inhibitory efficacy determined by Scintillation Proximity Assay detecting phosphorylated lipid substrates after incubation with recombinant PI3Kδ and radioactive ATP.
PIK-108 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Negative 6.2 pIC50 18
⤷ pIC50 6.2 (IC50 6.58x10-7 M) [18]
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: 24,86
Key to terms and symbols Click column headers to sort
Target used in screen: PIK3CD
Ligand Sp. Type Action Value Parameter
pictilisib 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 7.5 pKd
TG-100-115 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand 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
linifanib Small molecule or natural product Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [37], with selective PI3Kδ inhibitors of particular relevance- see for example AMG319 [22], leniolisib [20] and seletalisib [3].
The PI3Kδ isoform is of particular therapeutic interest in chronic obstructive airway diseases, such as severe asthma and COPD given its signalling role in regulating neutrophil superoxide generation.
The potential for PI3kδ as a druggable target in immuno-oncology and chronic obstructive airway diseases is discussed in [1] and [61], respectively.
Cell Type Associations
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
References:  83
Immuno Cell Type:  T cells
Cell Ontology Term:   alpha-beta T cell (CL:0000789)
References:  83
Immuno Process Associations
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 3 GO processes
GO:0002250 adaptive immune response TAS
GO:0030183 B cell differentiation NAS
GO:0042113 B cell activation TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 9 GO processes
GO:0001779 natural killer cell differentiation TAS
GO:0030101 natural killer cell activation TAS
GO:0030183 B cell differentiation NAS
GO:0030217 T cell differentiation TAS
GO:0042110 T cell activation TAS
GO:0042113 B cell activation TAS
GO:0043303 mast cell degranulation TAS
GO:0050852 T cell receptor signaling pathway TAS
GO:0050853 B cell receptor signaling pathway TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 6 GO processes
GO:0002551 mast cell chemotaxis TAS
GO:0010818 T cell chemotaxis TAS
GO:0030593 neutrophil chemotaxis TAS
GO:0035747 natural killer cell chemotaxis TAS
GO:0035754 B cell chemotaxis TAS
GO:0072672 neutrophil extravasation TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0001819 positive regulation of cytokine production TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0033031 positive regulation of neutrophil apoptotic process IMP
GO:0050852 T cell receptor signaling pathway TAS
GO:0050853 B cell receptor signaling pathway TAS
Immuno Process:  Immune system development
GO Annotations:  Associated to 3 GO processes
GO:0001779 natural killer cell differentiation TAS
GO:0030183 B cell differentiation NAS
GO:0030217 T cell differentiation TAS
Immuno Process:  Inflammation
GO Annotations:  Associated to 9 GO processes
GO:0002551 mast 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:0035754 B cell chemotaxis TAS
GO:0043303 mast cell degranulation TAS
GO:0045087 innate immune response TAS
GO:0072672 neutrophil extravasation TAS
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 3 GO processes
GO:0002250 adaptive immune response TAS
GO:0030217 T cell differentiation TAS
GO:0042110 T cell activation TAS
Immuno Disease Associations
Disease Name:  Activated PI3K delta syndrome
Disease Synonyms:  no synonynms
Comment:  The effects of constitutive PI3Kδ activation in this syndrome are the opposite (or inverse) of the effects mediated by pharmacological PI3Kδ inhibition.
Disease X-refs:  OMIM: 615513
Orphanet: ORPHA397596
References: 
Tissue Distribution Click here for help
Leukocytes
Species:  Human
Technique:  Northern blot
References:  83
Lymphoid and myeloid cell populations, T cells, B cells (N.B. platelets negative)
Species:  Human
Technique:  Immunocytochemistry
References:  83
Spleen and thymus
Species:  Rat
Technique:  Immunohistochemistry
References:  83
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Activated PI3K delta syndrome
Description: A rare autosomal dominant, genetic disease causing primary immunodeficiency and characterised by lymphadenopathy, immunodeficiency leading to recurrent infections, and an increased risk of EBV-associated lymphoma.
Synonyms: APDS/PASLI
Immunodeficiency 14
p110 delta activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency
OMIM: 615513
Orphanet: ORPHA397596
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense, gain of function Human Y524N 1570 T>A This is a de novo pathogenic GOF mutation in the helical domain of PI3Kδ discovered in a 6-year-old patient with APDS. 58
Missense, gain of function Human N334K; E525K; E1021K 1002 C>A; 1573 G>A; 3061 G>A N334K is in the C2 domain, E525K is in the helical domain and E1021K is in the C-lobe of the kinase domain. 57
Clinically-Relevant Mutations and Pathophysiology Comments
To date (August 2018) eleven missense disease-causing variants of PIK3δ have been identified in the various functional domains of the kinase:
R929C [84], E1021K [4], and E1025G [27] in the kinase domain
N334 K [57], C416R [21], and R405C [70] in the C2 domain
E525K [57], E525A [80] and Y524N [58] in the helical domain
E81K [78] in the adaptor-binding domain (ABD)
G124D [78] in the ABD-Ras-binding domain linker
General Comments
PI3Kδ belongs to the class IA phospho-inositide-3-kinases (PI3Ks). In common with PI3Kα and PI3Kβ, PI3Kδ displays a broad phosphoinositide lipid substrate specificity. It interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. Expression of PI3Kδ is restricted to leukocytes [83], whereas PI3Kα and PI3Kβ are widely expressed.

References

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