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

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

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

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

   GtoImmuPdb view: ON :     phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1044 1p36.2 PIK3CD phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta 59
Mouse - 1047 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
PI3Kdelta | p110δ/PIK3CD | phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta | phosphatidylinositol-4 | phosphatidylinositol 3-kinase catalytic delta polypeptide
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
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
Resolution:  2.8Å
Species:  Mouse
References:  13
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:  8
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 Affinity Units Reference
compound 20f [PMID: 28520415] Hs Inhibition 9.2 pIC50 48
pIC50 9.2 (IC50 6.3x10-10 M) [48]
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
IPI549 Hs Inhibition 7.6 pKd 22
pKd 7.6 (Kd 2.3x10-8 M) [22]
bimiralisib Hs Inhibition 7.6 pKd
pKd 7.6 (Kd 2.5x10-8 M)
LY 294002 Hs Inhibition 6.2 pKd 19
pKd 6.2 (Kd 7.1x10-7 M) [19]
taselisib Hs Inhibition 9.7 – 10.1 pKi 9,43
pKi 10.1 (Ki 7.9x10-11 M) [9]
pKi 9.7 (Ki 2.1x10-10 M) [43]
compound 82 [PMID: 21332118] Hs Inhibition 8.9 pKi 17
pKi 8.9 (Ki 1.2x10-9 M) [17]
pictilisib Hs Inhibition 8.8 pKi 9
pKi 8.8 (Ki 1.54x10-9 M) [9]
GDC-0077 Hs Inhibition 7.9 pKi 9
pKi 7.9 (Ki 1.22x10-8 M) [9]
IC-87114 Hs Inhibition ~7.7 pKi 34
pKi ~7.7 (Ki ~2x10-8 M) [34]
omipalisib Hs Inhibition 7.2 pKi 32
pKi 7.2 (Ki 6x10-8 M) [32]
KU-0060648 Hs Inhibition >10.0 pIC50 11
pIC50 >10.0 (IC50 <1x10-10 M) [11]
nemiralisib Hs Inhibition 9.9 pIC50 20
pIC50 9.9 (IC50 1.26x10-10 M) [20]
Description: In a homogeneous time-resolved fluorescence (HTRF) assay in the presence of 2mM ATP.
compound 52 [PMID: 28541707] Hs Inhibition 8.8 pIC50 38
pIC50 8.8 (IC50 1.7x10-9 M) [38]
idelalisib Hs Inhibition 8.6 pIC50 35
pIC50 8.6 (IC50 2.5x10-9 M) in vitro activity against recombinant enzyme [35]
duvelisib Hs Inhibition 8.6 pIC50 61
pIC50 8.6 (IC50 2.5x10-9 M) [61]
pictilisib Hs Inhibition 8.5 pIC50 23
pIC50 8.5 (IC50 3x10-9 M) [23]
PI-103 Hs Inhibition 8.5 pIC50 51
pIC50 8.5 (IC50 3x10-9 M) [51]
puquitinib Hs Inhibition 8.5 pIC50 64
pIC50 8.5 (IC50 3.3x10-9 M) [64]
panulisib Hs Inhibition 8.4 pIC50 31
pIC50 8.4 (IC50 4x10-9 M) [31]
Description: Using a radiometric protein kinase (33PanQinase activity) assay.
ZSTK474 Hs Inhibition 8.2 – 8.3 pIC50 63,65
pIC50 8.2 – 8.3 (IC50 6x10-9 – 5x10-9 M) [63,65]
torin 2 Hs Inhibition 8.3 pIC50 39
pIC50 8.3 (IC50 5.67x10-9 M) [39]
AZD8835 Hs Inhibition 8.2 pIC50 7
pIC50 8.2 (IC50 5.7x10-9 M) [7]
apitolisib Hs Inhibition 8.2 pIC50 54
pIC50 8.2 (IC50 6.7x10-9 M) [54]
dactolisib Hs Inhibition 8.1 pIC50 42
pIC50 8.1 (IC50 7x10-9 M) [42]
AZD8186 Hs Inhibition 7.9 pIC50 26
pIC50 7.9 (IC50 1.2x10-8 M) [26]
seletalisib Hs Inhibition 7.9 pIC50 3
pIC50 7.9 (IC50 1.2x10-8 M) [3]
TGR-1202 Hs Inhibition 7.9 pIC50 58
pIC50 7.9 (IC50 1.383x10-8 M) [58]
PI-3065 Hs Inhibition 7.8 pIC50 2
pIC50 7.8 (IC50 1.5x10-8 M) [2]
AMG319 Hs Inhibition 7.7 pIC50 16
pIC50 7.7 (IC50 1.8x10-8 M) [16]
leniolisib Hs Inhibition 7.6 pIC50 14
pIC50 7.6 (IC50 2.3x10-8 M) [14]
Description: In vitro enzyme assay
tenalisib Hs Inhibition 7.6 pIC50 57
pIC50 7.6 (IC50 2.405x10-8 M) [57]
Description: In a high throughput biochemical assay.
pilaralisib Hs Inhibition 7.4 pIC50 63
pIC50 7.4 (IC50 3.6x10-8 M) [63]
LY3023414 Hs Inhibition 7.4 pIC50 6
pIC50 7.4 (IC50 3.8x10-8 M) [6]
fimepinostat Hs Inhibition 7.4 pIC50 49
pIC50 7.4 (IC50 3.9x10-8 M) [49]
VS-5584 Hs Inhibition 7.4 pIC50 28
pIC50 7.4 (IC50 4.2x10-8 M) [28]
dezapelisib Hs Inhibition >7.3 pIC50 36
pIC50 >7.3 (IC50 <5x10-8 M) [36]
Description: The same value was obtained using an enzyme activity assay and a scintillation proximity assay.
AZD6482 Hs Inhibition 7.1 pIC50 44
pIC50 7.1 (IC50 8x10-8 M) [44]
TGX-221 Hs Inhibition 7.0 pIC50 30
pIC50 7.0 (IC50 1x10-7 M) [30]
PP121 Hs Inhibition 6.8 pIC50 5
pIC50 6.8 (IC50 1.5x10-7 M) [5]
LY 294002 Hs Inhibition 6.7 pIC50 11
pIC50 6.7 (IC50 2.2x10-7 M) [11]
sapanisertib Hs Inhibition 6.6 pIC50 29
pIC50 6.6 (IC50 2.3x10-7 M) [29]
TG-100-115 Hs Inhibition 6.6 pIC50 46
pIC50 6.6 (IC50 2.35x10-7 M) [46]
alpelisib Hs Inhibition 6.5 pIC50 25
pIC50 6.5 (IC50 2.9x10-7 M) [25]
PI 3-Kg inhibitor Hs Inhibition 6.5 pIC50 10
pIC50 6.5 (IC50 3x10-7 M) [10]
compound 15 [PMID: 29852070] Hs Inhibition 6.5 pIC50 47
pIC50 6.5 (IC50 3.16x10-7 M) [47]
Description: In a biochemical enzyme activity assay.
compound 28 [PMID: 24387221] Hs Inhibition 6.3 pIC50 12
pIC50 6.3 (IC50 4.68x10-7 M) [12]
CH5132799 Hs Inhibition 6.3 pIC50 45
pIC50 6.3 (IC50 5x10-7 M) [45]
IC-87114 Hs Inhibition 6.3 pIC50 53
pIC50 6.3 (IC50 5x10-7 M) [53]
PIK-75 Hs Inhibition 6.3 pIC50 33
pIC50 6.3 (IC50 5.1x10-7 M) [33]
STK16-IN-1 Hs Inhibition 6.1 pIC50 37
pIC50 6.1 (IC50 8.56x10-7 M) [37]
Description: In an in vitro enzymatic assay.
eCF309 Hs Inhibition 5.7 pIC50 24
pIC50 5.7 (IC50 1.84x10-6 M) [24]
Description: In a biochemical assay.
serabelisib Hs Inhibition >5.0 pIC50 52
pIC50 >5.0 (IC50 <1x10-5 M) [52]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
PIK-108 Hs Negative 6.2 pIC50 13
pIC50 6.2 (IC50 6.58x10-7 M) [13]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 18,62

Key to terms and symbols Click column headers to sort
Target used in screen: PIK3CD
Ligand Sp. Type Action Affinity Units
pictilisib Hs Inhibitor Inhibition 8.3 pKd
PI-103 Hs Inhibitor Inhibition 7.8 pKd
PP-242 Hs Inhibitor Inhibition 7.5 pKd
TG-100-115 Hs Inhibitor Inhibition 6.6 pKd
ruboxistaurin Hs Inhibitor Inhibition <5.5 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
erlotinib Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Hs Inhibitor Inhibition <5.5 pKd
masitinib Hs Inhibitor Inhibition <5.5 pKd
A-674563 Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Tissue Distribution
Species:  Human
Technique:  Northern blot
References:  59
Lymphoid and myeloid cell populations, T cells, B cells (N.B. platelets negative)
Species:  Human
Technique:  Immunocytochemistry
References:  59
Spleen and thymus
Species:  Rat
Technique:  Immunohistochemistry
References:  59
Clinically-Relevant Mutations and Pathophysiology
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. 41
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. 40
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 [60], E1021K [4], and E1025G [21] in the kinase domain
N334 K [40], C416R [15], and R405C [50] in the C2 domain
E525K [40], E525A [56] and Y524N [41] in the helical domain
E81K [55] in the adaptor-binding domain (ABD)
G124D [55] 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 [59], whereas PI3Kα and PI3Kβ are widely expressed.


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Phosphatidylinositol-4,5-bisphosphate 3-kinase family: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta. Last modified on 29/08/2018. Accessed on 16/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY,