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

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

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

   GtoImmuPdb view: OFF :     Currently no data for phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1070 3q21-qter PIK3CB phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta
Mouse - 1064 9 E4 Pik3cb phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta
Rat - 1070 8 q31 Pik3cb phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta
Previous and Unofficial Names
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
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.1.153

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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
PQR309 Hs Inhibition 8.0 pKd
pKd 8.0 (Kd 1.1x10-8 M)
IPI549 Hs Inhibition 7.1 pKd 15
pKd 7.1 (Kd 8.2x10-8 M) [15]
LY 294002 Hs Inhibition 6.6 pKd 13
pKd 6.6 (Kd 2.7x10-7 M) [13]
compound 82 [PMID: 21332118] Hs Inhibition 8.7 pKi 11
pKi 8.7 (Ki 2x10-9 M) [11]
taselisib Hs Inhibition 7.3 – 8.0 pKi 5,26
pKi 8.0 (Ki 9.1x10-9 M) [26]
pKi 7.3 (Ki 5.3x10-8 M) [5]
pictilisib Hs Inhibition 7.2 pKi 5
pKi 7.2 (Ki 7.02x10-8 M) [5]
GDC-0077 Hs Inhibition 7.0 pKi 5
pKi 7.0 (Ki 9.97x10-8 M) [5]
omipalisib Hs Inhibition 6.9 pKi 22
pKi 6.9 (Ki 1.3x10-7 M) [22]
KU-0060648 Hs Inhibition 9.3 pIC50 7
pIC50 9.3 (IC50 5x10-10 M) [7]
PI-103 Hs Inhibition 8.5 pIC50 31
pIC50 8.5 (IC50 3x10-9 M) [31]
AZD8186 Hs Inhibition 8.4 pIC50 18
pIC50 8.4 (IC50 4x10-9 M) [18]
TGX-221 Hs Inhibition 8.3 pIC50 21
pIC50 8.3 (IC50 5x10-9 M) [21]
AZD6482 Hs Inhibition 8.0 pIC50 27
pIC50 8.0 (IC50 1x10-8 M) [27]
compound 28 [PMID: 24387221] Hs Inhibition 7.6 pIC50 8
pIC50 7.6 (IC50 2.3x10-8 M) [8]
apitolisib Hs Inhibition 7.6 pIC50 33
pIC50 7.6 (IC50 2.7x10-8 M) [33]
ZSTK474 Hs Inhibition 7.4 – 7.8 pIC50 36-37
pIC50 7.4 – 7.8 (IC50 4.4x10-8 – 1.7x10-8 M) [36-37]
pictilisib Hs Inhibition 7.5 pIC50 16
pIC50 7.5 (IC50 3.3x10-8 M) [16]
CUDC-907 Hs Inhibition 7.3 pIC50 30
pIC50 7.3 (IC50 5.4x10-8 M) [30]
BGT-226 Hs Inhibition 7.2 pIC50 25
pIC50 7.2 (IC50 6.3x10-8 M) [25]
VS-5584 Hs Inhibition 7.2 pIC50 19
pIC50 7.2 (IC50 6.8x10-8 M) [19]
LY3023414 Hs Inhibition 7.1 pIC50 3
pIC50 7.1 (IC50 7.8x10-8 M) [3]
duvelisib Hs Inhibition 7.1 pIC50 34
pIC50 7.1 (IC50 8.5x10-8 M) [34]
CH5132799 Hs Inhibition 6.9 pIC50 28
pIC50 6.9 (IC50 1.2x10-7 M) [28]
LY 294002 Hs Inhibition 6.6 pIC50 7
pIC50 6.6 (IC50 2.7x10-7 M) [7]
PI 3-Kg inhibitor Hs Inhibition 6.6 pIC50 6
pIC50 6.6 (IC50 2.7x10-7 M) [6]
pilaralisib Hs Inhibition 6.4 pIC50 36
pIC50 6.4 (IC50 3.83x10-7 M) [36]
AZD8835 Hs Inhibition 6.4 pIC50 4
pIC50 6.4 (IC50 4.31x10-7 M) [4]
idelalisib Hs Inhibition 6.3 pIC50 24
pIC50 6.3 (IC50 5.65x10-7 M) [24]
PIK-75 Hs Inhibition 5.9 – 6.1 pIC50 20,23
pIC50 6.1 (IC50 8.5x10-7 M) [20]
pIC50 5.9 (IC50 1.3x10-6 M) [23]
PI-3065 Hs Inhibition 6.0 pIC50 1
pIC50 6.0 (IC50 1.078x10-6 M) [1]
TG-100-115 Hs Inhibition 5.9 pIC50 29
pIC50 5.9 (IC50 1.2x10-6 M) [29]
alpelisib Hs Inhibition 5.9 pIC50 17
pIC50 5.9 (IC50 1.2x10-6 M) [17]
PP121 Hs Inhibition 5.8 pIC50 2
pIC50 5.8 (IC50 1.4x10-6 M) [2]
nemiralisib Hs Inhibition 5.8 pIC50 14
pIC50 5.8 (IC50 1.584x10-6 M) [14]
Description: In a homogeneous time-resolved fluorescence (HTRF) assay
AMG319 Hs Inhibition 5.6 pIC50 10
pIC50 5.6 (IC50 2.7x10-6 M) [10]
serabelisib Hs Inhibition >5.0 pIC50 32
pIC50 >5.0 (IC50 <1x10-5 M) [32]
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 7.6 pIC50 9
pIC50 7.6 (IC50 2.8x10-8 M) [9]
DiscoveRx KINOMEscan® screen
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: 12,35

Key to terms and symbols Click column headers to sort
Target used in screen: PIK3CB
Ligand Sp. Type Action Affinity Units
PI-103 Hs Inhibitor Inhibition 8.8 pKd
pictilisib Hs Inhibitor Inhibition 7.8 pKd
TG-100-115 Hs Inhibitor Inhibition 7.1 pKd
PP-242 Hs Inhibitor Inhibition 6.9 pKd
GSK-461364A Hs Inhibitor Inhibition 5.7 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Hs Inhibitor Inhibition <5.5 pKd
erlotinib Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Hs Inhibitor Inhibition <5.5 pKd
masitinib Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Nature510 (7505): 407-11. [PMID:24919154]

2. 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]

3. 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.

4. 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]

5. 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.

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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 Lett7 (9): 862-7. [PMID:27660692]

16. 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]

17. 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]

18. 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]

19. 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]

20. 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]

21. 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]

22. 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 Lett1 (1): 39-43. [PMID:24900173]

23. 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. Cell125 (4): 733-47. [PMID:16647110]

24. 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. Blood117 (2): 591-4. [PMID:20959606]

25. 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]

26. 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]

27. 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]

28. 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]

29. 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]

30. 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]

31. 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]

32. 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.

33. 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]

34. 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]

35. 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]

36. Wu P, Hu Y. (2012) Small molecules targeting phosphoinositide 3-kinases. Med. Chem. Commun.3 (11): 1337-1355.

37. 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]

How to cite this page

Phosphatidylinositol kinases: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta. Last modified on 15/08/2017. Accessed on 17/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2154.