Top ▲

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

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 2154

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

Abbreviated Name: PI3Kβ

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 - 1070 3q22.3 PIK3CB phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta
Mouse - 1064 9 E3.3 Pik3cb phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta
Rat - 1070 8q31 Pik3cb phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta
Previous and Unofficial Names Click here for help
PI3Kbeta | PI3-kinase p110 subunit beta | PIK3C1 | phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform | ptdIns-3-kinase p110 | p110β/PIK3CB | phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta | phosphatidylinositol-4
Database Links Click here for help
Alphafold P42338 (Hs), Q8BTI9 (Mm), Q9Z1L0 (Rn)
BRENDA 2.7.1.153
CATH/Gene3D 2.60.40.150, 1.10.1070.11
ChEMBL Target CHEMBL3145 (Hs), CHEMBL4739696 (Mm), CHEMBL3608198 (Rn)
Ensembl Gene ENSG00000051382 (Hs), ENSMUSG00000032462 (Mm), ENSRNOG00000016384 (Rn)
Entrez Gene 5291 (Hs), 74769 (Mm), 85243 (Rn)
Human Protein Atlas ENSG00000051382 (Hs)
KEGG Enzyme 2.7.1.153
KEGG Gene hsa:5291 (Hs), mmu:74769 (Mm), rno:85243 (Rn)
OMIM 602925 (Hs)
Pharos P42338 (Hs)
RefSeq Nucleotide NM_001256045 (Hs), NM_029094 (Mm), NM_053481 (Rn)
RefSeq Protein NP_006210 (Hs), NP_083370 (Mm), NP_445933 (Rn)
UniProtKB P42338 (Hs), Q8BTI9 (Mm), Q9Z1L0 (Rn)
Wikipedia PIK3CB (Hs)
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
neolymphostin A Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pKd 12
⤷ pKd 8.2 (Kd 5.7x10-9 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 8.1 pKd 12
⤷ pKd 8.1 (Kd 7.6x10-9 M) [12]
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 8.0 pKd
⤷ pKd 8.0 (Kd 1.1x10-8 M)
eganelisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pKd 21
⤷ pKd 7.1 (Kd 8.2x10-8 M) [21]
LY 294002 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pKd 19
⤷ pKd 6.6 (Kd 2.7x10-7 M) [19]
compound 12b [PMID: 31465220] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.1 pKd 7
⤷ pKd 5.1 (Kd 7.5x10-6 M) [7]
compound 82 [PMID: 21332118] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pKi 17
⤷ pKi 8.7 (Ki 2x10-9 M) [17]
PF-06843195 Small molecule or natural product 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]
taselisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 – 8.0 pKi 8,42
⤷ pKi 8.0 (Ki 9.1x10-9 M) [42]
pKi 7.3 (Ki 5.3x10-8 M) [8]
pictilisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pKi 8
⤷ pKi 7.2 (Ki 7.02x10-8 M) [8]
inavolisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pKi 8
⤷ pKi 7.0 (Ki 9.97x10-8 M) [8]
omipalisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.9 pKi 34
⤷ pKi 6.9 (Ki 1.3x10-7 M) [34]
AZD8154 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.9 pKi 47
⤷ pKi 5.9 (Ki 1.362x10-6 M) [47]
KU-0060648 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.3 pIC50 11
⤷ pIC50 9.3 (IC50 5x10-10 M) [11]
compound 15a [PMID: 32069401] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.2 pIC50 62
⤷ pIC50 9.2 (IC50 5.8x10-10 M) [62]
compound 5d [PMID: 31335136] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 38
⤷ pIC50 9.1 (IC50 7x10-10 M) [38]
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 50
⤷ pIC50 8.5 (IC50 3x10-9 M) [50]
copanlisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 39
⤷ pIC50 8.4 (IC50 3.7x10-9 M) [39]
AZD8186 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 26
⤷ pIC50 8.4 (IC50 4x10-9 M) [26]
TGX-221 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pIC50 31
⤷ pIC50 8.3 (IC50 5x10-9 M) [31]
NVP-CLR457 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 22
⤷ pIC50 8.1 (IC50 8.3x10-9 M) [22]
AZD6482 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 43
⤷ pIC50 8.0 (IC50 1x10-8 M) [43]
SAR260301 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 pIC50 13
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [13]
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 7.6 pIC50 54
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [54]
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 7.4 – 7.8 pIC50 59,61
⤷ pIC50 7.4 – 7.8 (IC50 4.4x10-8 – 1.7x10-8 M) [59,61]
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 7.5 pIC50 23
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [23]
fimepinostat Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 49
⤷ pIC50 7.3 (IC50 5.4x10-8 M) [49]
BGT-226 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.2 pIC50 40
⤷ pIC50 7.2 (IC50 6.3x10-8 M) [40]
VS-5584 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.2 pIC50 27
⤷ pIC50 7.2 (IC50 6.8x10-8 M) [27]
samotolisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 4
⤷ pIC50 7.1 (IC50 7.8x10-8 M) [4]
compound 20f [PMID: 28520415] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 48
⤷ pIC50 7.1 (IC50 7.94x10-8 M) [48]
duvelisib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 57
⤷ pIC50 7.1 (IC50 8.5x10-8 M) [57]
amdizalisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 53
⤷ pIC50 7.1 (IC50 8.7x10-8 M) [53]
BAY-8400 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.9 pIC50 6
⤷ pIC50 6.9 (IC50 1.17x10-7 M) [6]
izorlisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.9 pIC50 44
⤷ pIC50 6.9 (IC50 1.2x10-7 M) [44]
compound 27 [PMID: 35834807] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 30
⤷ pIC50 6.8 (IC50 1.46x10-7 M) [30]
vulolisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 63
⤷ pIC50 6.8 (IC50 1.68x10-7 M) [63]
panulisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 32
⤷ pIC50 6.8 (IC50 1.76x10-7 M) [32]
Description: Using a radiometric protein kinase (33PanQinase activity) assay.
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 6.6 pIC50 11
⤷ pIC50 6.6 (IC50 2.7x10-7 M) [11]
PI 3-Kg inhibitor Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 10
⤷ pIC50 6.6 (IC50 2.7x10-7 M) [10]
zandelisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 – 6.7 pIC50 9
⤷ pIC50 6.3 – 6.7 (IC50 5x10-7 – 2x10-7 M) [9]
Description: Binned value from patent.
pilaralisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 59
⤷ pIC50 6.4 (IC50 3.83x10-7 M) [59]
AZD8835 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 5
⤷ pIC50 6.4 (IC50 4.31x10-7 M) [5]
dezapelisib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition <6.3 pIC50 37
⤷ pIC50 <6.3 (IC50 >5x10-7 M) [37]
idelalisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.3 pIC50 36
⤷ pIC50 6.3 (IC50 5.65x10-7 M) [36]
puquitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pIC50 60
⤷ pIC50 6.0 (IC50 9.592x10-7 M) [60]
PIK-75 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.9 – 6.1 pIC50 28,35
⤷ pIC50 6.1 (IC50 8.5x10-7 M) [28]
pIC50 5.9 (IC50 1.3x10-6 M) [35]
PI-3065 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pIC50 1
⤷ pIC50 6.0 (IC50 1.078x10-6 M) [1]
DS-7423 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.9 pIC50 33
⤷ pIC50 5.9 (IC50 1.143x10-6 M) [33]
TG-100-115 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.9 pIC50 45
⤷ pIC50 5.9 (IC50 1.2x10-6 M) [45]
alpelisib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.9 pIC50 24
⤷ pIC50 5.9 (IC50 1.2x10-6 M) [24]
PP121 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.8 pIC50 3
⤷ pIC50 5.8 (IC50 1.4x10-6 M) [3]
nemiralisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.8 pIC50 20
⤷ pIC50 5.8 (IC50 1.584x10-6 M) [20]
Description: In a homogeneous time-resolved fluorescence (HTRF) assay
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 5.7 pIC50 29
⤷ pIC50 5.7 (IC50 1.995x10-6 M) [29]
seletalisib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.7 pIC50 2
⤷ pIC50 5.7 (IC50 2.129x10-6 M) [2]
AMG319 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.6 pIC50 16
⤷ pIC50 5.6 (IC50 2.7x10-6 M) [16]
acalisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.5 pIC50 52
⤷ pIC50 5.5 (IC50 3.377x10-6 M) [52]
Description: In an in vitro biochemical assay using recombinant enzyme.
tenalisib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition <5.4 pIC50 56
⤷ pIC50 <5.4 (IC50 >4x10-6 M) [56]
Description: In a high throughput biochemical assay.
RV6153 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.3 pIC50 55
⤷ pIC50 5.3 (IC50 4.89x10-6 M) [55]
Description: In a biochemical enzyme activity assay.
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 5.3 pIC50 41
⤷ pIC50 5.3 (IC50 5.46x10-6 M) [41]
Description: In a biochemical HTRF assay measuring generation of PIP3 via phosphorylation of PIP2, using PI3Kβ 14-603 fragment.
serabelisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition >5.0 pIC50 51
⤷ pIC50 >5.0 (IC50 <1x10-5 M) [51]
AZD3458 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition <4.5 pIC50 46
⤷ pIC50 <4.5 (IC50 >3.16x10-5 M) [46]
Description: In a biochemical enzyme activity assay.
AZ2 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 4.5 pIC50 25
⤷ pIC50 4.5 (IC50 3.162x10-5 M) [25]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PIK-108 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Negative 7.6 pIC50 14
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [14]
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: 18,58
Key to terms and symbols Click column headers to sort
Target used in screen: PIK3CB
Ligand Sp. Type Action Value Parameter
PI-103 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
pictilisib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
TG-100-115 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 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
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
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Antigen presentation
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling

References

Show »

1. Ali K, Soond DR, Piñeiro R, Hagemann T, Pearce W, Lim EL, Bouabe H, Scudamore CL, Hancox T, Maecker H et al.. (2014) Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer. Nature, 510 (7505): 407-11. [PMID:24919154]

2. 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]

3. 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]

4. 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.

5. 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]

6. Berger M, Wortmann L, Buchgraber P, Lücking U, Zitzmann-Kolbe S, Wengner AM, Bader B, Bömer U, Briem H, Eis K et al.. (2021) BAY-8400: A Novel Potent and Selective DNA-PK Inhibitor which Shows Synergistic Efficacy in Combination with Targeted Alpha Therapies. J Med Chem, 64 (17): 12723-12737. [PMID:34428039]

7. Borsari C, Rageot D, Dall'Asen A, Bohnacker T, Melone A, Sele AM, Jackson E, Langlois JB, Beaufils F, Hebeisen P et al.. (2019) A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor. J Med Chem, 62 (18): 8609-8630. [PMID:31465220]

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. Certal V, Carry JC, Halley F, Virone-Oddos A, Thompson F, Filoche-Rommé B, El-Ahmad Y, Karlsson A, Charrier V, Delorme C et al.. (2014) Discovery and optimization of pyrimidone indoline amide PI3Kβ inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers. J Med Chem, 57 (3): 903-20. [PMID:24387221]

14. Certal V, Halley F, Virone-Oddos A, Delorme C, Karlsson A, Rak A, Thompson F, Filoche-Rommé B, El-Ahmad Y, Carry JC et al.. (2012) Discovery and optimization of new benzimidazole- and benzoxazole-pyrimidone selective PI3Kβ inhibitors for the treatment of phosphatase and TENsin homologue (PTEN)-deficient cancers. J Med Chem, 55 (10): 4788-805. [PMID:22524426]

15. Cheng H, Orr STM, Bailey S, Brooun A, Chen P, Deal JG, Deng YL, Edwards MP, Gallego GM, Grodsky N et al.. (2021) Structure-Based Drug Design and Synthesis of PI3Kα-Selective Inhibitor (PF-06843195). J Med Chem, 64 (1): 644-661. [PMID:33356246]

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]

17. D'Angelo ND, Kim TS, Andrews K, Booker SK, Caenepeel S, Chen K, D'Amico D, Freeman D, Jiang J, Liu L et al.. (2011) Discovery and optimization of a series of benzothiazole phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors. J Med Chem, 54 (6): 1789-811. [PMID:21332118]

18. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

19. Dittmann A, Werner T, Chung CW, Savitski MM, Fälth Savitski M, Grandi P, Hopf C, Lindon M, Neubauer G, Prinjha RK et al.. (2014) The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains. ACS Chem Biol, 9 (2): 495-502. [PMID:24533473]

20. Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL et al.. (2015) Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem, 58 (18): 7381-99. [PMID:26301626]

21. Evans CA, Liu T, Lescarbeau A, Nair SJ, Grenier L, Pradeilles JA, Glenadel Q, Tibbitts T, Rowley AM, DiNitto JP et al.. (2016) Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate. ACS Med Chem Lett, 7 (9): 862-7. [PMID:27660692]

22. Fairhurst RA, Furet P, Imbach-Weese P, Stauffer F, Rueeger H, McCarthy C, Ripoche S, Oswald S, Arnaud B, Jary A et al.. (2022) Identification of NVP-CLR457 as an Orally Bioavailable Non-CNS-Penetrant pan-Class IA Phosphoinositol-3-Kinase Inhibitor. J Med Chem, 65 (12): 8345-8379. [PMID:35500094]

23. Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G, Chuckowree IS, Clarke PA, Depledge P, Eccles SA et al.. (2008) The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer . J Med Chem, 51 (18): 5522-32. [PMID:18754654]

24. Furet P, Guagnano V, Fairhurst RA, Imbach-Weese P, Bruce I, Knapp M, Fritsch C, Blasco F, Blanz J, Aichholz R et al.. (2013) Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett, 23 (13): 3741-8. [PMID:23726034]

25. Gangadhara G, Dahl G, Bohnacker T, Rae R, Gunnarsson J, Blaho S, Öster L, Lindmark H, Karabelas K, Pemberton N et al.. (2019) A class of highly selective inhibitors bind to an active state of PI3Kγ. Nat Chem Biol, 15 (4): 348-357. [PMID:30718815]

26. Hancox U, Cosulich S, Hanson L, Trigwell C, Lenaghan C, Ellston R, Dry H, Crafter C, Barlaam B, Fitzek M et al.. (2015) Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN-deficient breast and prostate tumors alone and in combination with docetaxel. Mol Cancer Ther, 14 (1): 48-58. [PMID:25398829]

27. Hart S, Novotny-Diermayr V, Goh KC, Williams M, Tan YC, Ong LC, Cheong A, Ng BK, Amalini C, Madan B et al.. (2013) VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther, 12 (2): 151-61. [PMID:23270925]

28. Hayakawa M, Kawaguchi K, Kaizawa H, Koizumi T, Ohishi T, Yamano M, Okada M, Ohta M, Tsukamoto S, Raynaud FI et al.. (2007) Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors. Bioorg Med Chem, 15 (17): 5837-44. [PMID:17601739]

29. Henley ZA, Amour A, Barton N, Bantscheff M, Bergamini G, Bertrand SM, Convery M, Down K, Dümpelfeld B, Edwards CD et al.. (2020) Optimization of Orally Bioavailable PI3Kδ Inhibitors and Identification of Vps34 as a Key Selectivity Target. J Med Chem, 63 (2): 638-655. DOI: 10.1021/acs.jmedchem.9b01585 [PMID:31855425]

30. Hou Y, Zhang F, Min W, Yuan K, Kuang W, Wang X, Zhu Y, Sun C, Xia F, Wang Y et al.. (2022) Discovery of Novel Phosphoinositide-3-Kinase α Inhibitors with High Selectivity, Excellent Bioavailability, and Long-Acting Efficacy for Gastric Cancer. J Med Chem, 65 (14): 9873-9892. [PMID:35834807]

31. Jackson SP, Schoenwaelder SM, Goncalves I, Nesbitt WS, Yap CL, Wright CE, Kenche V, Anderson KE, Dopheide SM, Yuan Y et al.. (2005) PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med, 11 (5): 507-14. [PMID:15834429]

32. Jalota-Badhwar A, Bhatia DR, Boreddy S, Joshi A, Venkatraman M, Desai N, Chaudhari S, Bose J, Kolla LS, Deore V et al.. (2015) P7170: A Novel Molecule with Unique Profile of mTORC1/C2 and Activin Receptor-like Kinase 1 Inhibition Leading to Antitumor and Antiangiogenic Activity. Mol Cancer Ther, 14 (5): 1095-106. [PMID:25700704]

33. Kashiyama T, Oda K, Ikeda Y, Shiose Y, Hirota Y, Inaba K, Makii C, Kurikawa R, Miyasaka A, Koso T et al.. (2014) Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423. PLoS One, 9 (2): e87220. [PMID:24504419]

34. Knight SD, Adams ND, Burgess JL, Chaudhari AM, Darcy MG, Donatelli CA, Luengo JI, Newlander KA, Parrish CA, Ridgers LH et al.. (2010) Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin. ACS Med Chem Lett, 1 (1): 39-43. [PMID:24900173]

35. Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O, Loewith R, Stokoe D, Balla A, Toth B et al.. (2006) A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell, 125 (4): 733-47. [PMID:16647110]

36. Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M et al.. (2011) CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood, 117 (2): 591-4. [PMID:20959606]

37. Li Y-L, Metcalf BW, Combs AP. (2011) Pyrimidinones as PI3K inhibitors. Patent number: WO2011008487. Assignee: Incyte Corporation. Priority date: 29/06/2009. Publication date: 20/01/2011.

38. Lin S, Jin J, Liu Y, Tian H, Zhang Y, Fu R, Zhang J, Wang M, Du T, Ji M et al.. (2019) Discovery of 4-Methylquinazoline Based PI3K Inhibitors for the Potential Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem, 62 (19): 8873-8879. [PMID:31335136]

39. Liu N, Rowley BR, Bull CO, Schneider C, Haegebarth A, Schatz CA, Fracasso PR, Wilkie DP, Hentemann M, Wilhelm SM et al.. (2013) BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models. Mol Cancer Ther, 12 (11): 2319-30. [PMID:24170767]

40. Markman B, Tabernero J, Krop I, Shapiro GI, Siu L, Chen LC, Mita M, Melendez Cuero M, Stutvoet S, Birle D et al.. (2012) Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors. Ann Oncol, 23 (9): 2399-408. [PMID:22357447]

41. Methot JL, Zhou H, Kattar SD, McGowan MA, Wilson K, Garcia Y, Deng Y, Altman M, Fradera X, Lesburg C et al.. (2019) Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability. J Med Chem, 62 (9): 4370-4382. [PMID:30986068]

42. Ndubaku CO, Heffron TP, Staben ST, Baumgardner M, Blaquiere N, Bradley E, Bull R, Do S, Dotson J, Dudley D et al.. (2013) Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem, 56 (11): 4597-610. [PMID:23662903]

43. Nylander S, Kull B, Björkman JA, Ulvinge JC, Oakes N, Emanuelsson BM, Andersson M, Skärby T, Inghardt T, Fjellström O et al.. (2012) Human target validation of phosphoinositide 3-kinase (PI3K)β: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kβ inhibitor. J Thromb Haemost, 10 (10): 2127-36. [PMID:22906130]

44. Ohwada J, Ebiike H, Kawada H, Tsukazaki M, Nakamura M, Miyazaki T, Morikami K, Yoshinari K, Yoshida M, Kondoh O et al.. (2011) Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799. Bioorg Med Chem Lett, 21 (6): 1767-72. [PMID:21316229]

45. Palanki MS, Dneprovskaia E, Doukas J, Fine RM, Hood J, Kang X, Lohse D, Martin M, Noronha G, Soll RM et al.. (2007) Discovery of 3,3'-(2,4-diaminopteridine-6,7-diyl)diphenol as an isozyme-selective inhibitor of PI3K for the treatment of ischemia reperfusion injury associated with myocardial infarction. J Med Chem, 50 (18): 4279-94. [PMID:17685602]

46. Pemberton N, Mogemark M, Arlbrandt S, Bold P, Cox RJ, Gardelli C, Holden NS, Karabelas K, Karlsson J, Lever S et al.. (2018) Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors. J Med Chem, 61 (12): 5435-5441. [PMID:29852070]

47. Perry M, Karabelas K, Mogemark M, Bold P, Tyrchan C, Nikitidid A, Petersen J, Borjesson U. (2018) 5-[2-(pyridin-2-ylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1 h-isoindol-1 -one derivatives and their use as dual inhibitors of phosphatidylinositol 3-kinase delta & gamma. Patent number: WO2018055040A1. Assignee: Astrazeneca Ab. Priority date: 22/09/2016. Publication date: 29/03/2018.

48. Perry MWD, Björhall K, Bonn B, Carlsson J, Chen Y, Eriksson A, Fredlund L, Hao H, Holden NS, Karabelas K et al.. (2017) Design and Synthesis of Soluble and Cell-Permeable PI3Kδ Inhibitors for Long-Acting Inhaled Administration. J Med Chem, 60 (12): 5057-5071. [PMID:28520415]

49. Qian C, Lai CJ, Bao R, Wang DG, Wang J, Xu GX, Atoyan R, Qu H, Yin L, Samson M et al.. (2012) Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin Cancer Res, 18 (15): 4104-13. [PMID:22693356]

50. Raynaud FI, Eccles SA, Patel S, Alix S, Box G, Chuckowree I, Folkes A, Gowan S, De Haven Brandon A, Di Stefano F et al.. (2009) Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ther, 8 (7): 1725-38. [PMID:19584227]

51. Ren P, Liu Y, Li L, Chan K, Wilson TE, Campbell SF. (2013) Heterocyclic compounds and uses thereof. Patent number: US20130035324 A1. Assignee: Ren P, Liu Y, Li L, Chan K, Wilson TE, Campbell SF.. Priority date: 17/08/2009. Publication date: 07/02/2013.

52. Shugg RP, Thomson A, Tanabe N, Kashishian A, Steiner BH, Puri KD, Pereverzev A, Lannutti BJ, Jirik FR, Dixon SJ et al.. (2013) Effects of isoform-selective phosphatidylinositol 3-kinase inhibitors on osteoclasts: actions on cytoskeletal organization, survival, and resorption. J Biol Chem, 288 (49): 35346-57. [PMID:24133210]

53. Su W-G, Dai G, Zhang W, Deng W. (2016) Novel imidazopyridazine compounds and their use. Patent number: WO2016045591A1. Assignee: Hutchison Medipharma Limited. Priority date: 24/09/2014. Publication date: 31/03/2016.

54. Sutherlin DP, Bao L, Berry M, Castanedo G, Chuckowree I, Dotson J, Folks A, Friedman L, Goldsmith R, Gunzner J et al.. (2011) Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer. J Med Chem, 54 (21): 7579-87. [PMID:21981714]

55. Taddei DMA, Onions ST, Smith AJ, Copmans AH, Broeckx RLM. (2016) Phosphoinositide 3-kinase inhibitors. Patent number: US9227977B2. Assignee: Respivert Ltd. Priority date: 15/03/2013. Publication date: 05/01/2016.

56. Vakkalanka SKVS, Bhavar PK, Viswanadha S, Babu G. (2017) Dual selective PI3 delta and gamma kinase inhibitors. Patent number: US9790224B2. Assignee: Rhizen Pharmaceuticals SA. Priority date: 07/06/2013. Publication date: 17/10/2017.

57. Winkler DG, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, Pink MM, Proctor JL, Lussier J, Martin CM et al.. (2013) PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol, 20 (11): 1364-74. [PMID:24211136]

58. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

59. Wu P, Hu Y. (2012) Small molecules targeting phosphoinositide 3-kinases. Medchemcomm, 3 (11): 1337-1355. DOI: 10.1039/C2MD20044A

60. Xie C, He Y, Zhen M, Wang Y, Xu Y, Lou L. (2017) Puquitinib, a novel orally available PI3Kδ inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia. Cancer Sci, 108 (7): 1476-1484. [PMID:28418085]

61. Yaguchi S, Fukui Y, Koshimizu I, Yoshimi H, Matsuno T, Gouda H, Hirono S, Yamazaki K, Yamori T. (2006) Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J Natl Cancer Inst, 98 (8): 545-56. [PMID:16622124]

62. Yu Y, Han Y, Zhang F, Gao Z, Zhu T, Dong S, Ma M. (2020) Design, Synthesis, and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel PI3K/mTOR Dual Inhibitors. J Med Chem, 63 (6): 3028-3046. [PMID:32069401]

63. Zhan X, Su L. (2021) Three fused ring derivative-containing salt or crystal form and pharmaceutical composition thereof. Patent number: WO2021104146A1. Assignee: Shanghai Hansen Biomedical Technology, Jiangsu Hansen Pharmaceutical Group. Priority date: 25/11/2019. Publication date: 03/06/2021.

How to cite this page