Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHBTOP)

DTT Name	PI3-kinase gamma (PIK3CG)
Synonyms	p120-PI3K; p110gamma; Serine/threonine protein kinase PIK3CG; PtdIns-3-kinase subunit p110-gamma; PtdIns-3-kinase subunit gamma; PtdIns-3-kinase p110; Phosphoinositol-3 kinase; Phosphoinositide-3-kinase catalytic gamma polypeptide; Phosphoinositide 3-Kinase gamma; Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, gamma isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma; PI3Kgamma; PI3K-gamma; PI3K; PI3-kinase subunit gamma; PI3-kinase p110 subunit gamma
Gene Name	PIK3CG
DTT Type	Successful target	[1]
Related Disease	Follicular lymphoma [ICD-11: 2A80] Malignant haematopoietic neoplasm [ICD-11: 2B33] Mature B-cell leukaemia [ICD-11: 2A82]
BioChemical Class	Kinase
UniProt ID	PK3CG_HUMAN
TTD ID	T95913
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	EC 2.7.1.153
Sequence	MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLH VAGHGNVEQMKAQVWLRALETSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLD CLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGYDVTDVSNVHDDELEFTRRGL VTPRMAEVASRDPKLYAMHPWVTSKPLPEYLWKKIANNCIFIVIHRSTTSQTIKVSPDDT PGAILQSFFTKMAKKKSLMDIPESQSEQDFVLRVCGRDEYLVGETPIKNFQWVRHCLKNG EEIHVVLDTPPDPALDEVRKEEWPLVDDCTGVTGYHEQLTIHGKDHESVFTVSLWDCDRK FRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKI KDLPKGALLNLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEY VLHMWQISGKGEDQGSFNADKLTSATNPDKENSMSISILLDNYCHPIALPKHQPTPDPEG DRVRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQ QEIVAKTYQLLARREVWDQSALDVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYL LQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRHYQQRFAVILEAY LRGCGTAMLHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLP ESFRVPYDPGLKAGALAIEKCKVMASKKKPLWLEFKCADPTALSNETIGIIFKHGDDLRQ DMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQQSTVGNTG AFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNL FHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLAL RHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGW TVQFNWFLHLVLGIKQGEKHSA
Function	Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.
KEGG Pathway	Inositol phosphate metabolism (hsa00562 ) ErbB signaling pathway (hsa04012 ) Ras signaling pathway (hsa04014 ) Rap1 signaling pathway (hsa04015 ) cGMP-PKG signaling pathway (hsa04022 ) cAMP signaling pathway (hsa04024 ) Chemokine signaling pathway (hsa04062 ) HIF-1 signaling pathway (hsa04066 ) FoxO signaling pathway (hsa04068 ) Phosphatidylinositol signaling system (hsa04070 ) Sphingolipid signaling pathway (hsa04071 ) mTOR signaling pathway (hsa04150 ) PI3K-Akt signaling pathway (hsa04151 ) AMPK signaling pathway (hsa04152 ) Apoptosis (hsa04210 ) Adrenergic signaling in cardiomyocytes (hsa04261 ) VEGF signaling pathway (hsa04370 ) Osteoclast differentiation (hsa04380 ) Focal adhesion (hsa04510 ) Signaling pathways regulating pluripotency of stem cells (hsa04550 ) Platelet activation (hsa04611 ) Toll-like receptor signaling pathway (hsa04620 ) Jak-STAT signaling pathway (hsa04630 ) Natural killer cell mediated cytotoxicity (hsa04650 ) T cell receptor signaling pathway (hsa04660 ) B cell receptor signaling pathway (hsa04662 ) Fc epsilon RI signaling pathway (hsa04664 ) Fc gamma R-mediated phagocytosis (hsa04666 ) TNF signaling pathway (hsa04668 ) Leukocyte transendothelial migration (hsa04670 ) Neurotrophin signaling pathway (hsa04722 ) Cholinergic synapse (hsa04725 ) Inflammatory mediator regulation of TRP channels (hsa04750 ) Regulation of actin cytoskeleton (hsa04810 ) Insulin signaling pathway (hsa04910 ) Progesterone-mediated oocyte maturation (hsa04914 ) Estrogen signaling pathway (hsa04915 ) Prolactin signaling pathway (hsa04917 ) Thyroid hormone signaling pathway (hsa04919 ) Oxytocin signaling pathway (hsa04921 ) Regulation of lipolysis in adipocytes (hsa04923 ) Type II diabetes mellitus (hsa04930 ) Non-alcoholic fatty liver disease (NAFLD) (hsa04932 ) Aldosterone-regulated sodium reabsorption (hsa04960 ) Carbohydrate digestion and absorption (hsa04973 ) Bacterial invasion of epithelial cells (hsa05100 ) Chagas disease (American trypanosomiasis) (hsa05142 ) Toxoplasmosis (hsa05145 ) Amoebiasis (hsa05146 ) Hepatitis C (hsa05160 ) Hepatitis B (hsa05161 ) Measles (hsa05162 ) Influenza A (hsa05164 ) HTLV-I infection (hsa05166 ) Epstein-Barr virus infection (hsa05169 ) Pathways in cancer (hsa05200 ) Viral carcinogenesis (hsa05203 ) Proteoglycans in cancer (hsa05205 ) MicroRNAs in cancer (hsa05206 ) Colorectal cancer (hsa05210 ) Renal cell carcinoma (hsa05211 ) Pancreatic cancer (hsa05212 ) Endometrial cancer (hsa05213 ) Glioma (hsa05214 ) Prostate cancer (hsa05215 ) Melanoma (hsa05218 ) Chronic myeloid leukemia (hsa05220 ) Acute myeloid leukemia (hsa05221 ) Small cell lung cancer (hsa05222 ) Non-small cell lung cancer (hsa05223 ) Central carbon metabolism in cancer (hsa05230 ) Choline metabolism in cancer (hsa05231 )
Reactome Pathway	GPVI-mediated activation cascade (R-HSA-114604 ) Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382 ) PI3K events in ERBB4 signaling (R-HSA-1250342 ) PIP3 activates AKT signaling (R-HSA-1257604 ) GAB1 signalosome (R-HSA-180292 ) PI3K events in ERBB2 signaling (R-HSA-1963642 ) PI3K/AKT activation (R-HSA-198203 ) Role of phospholipids in phagocytosis (R-HSA-2029485 ) Tie2 Signaling (R-HSA-210993 ) Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 ) DAP12 signaling (R-HSA-2424491 ) Role of LAT2/NTAL/LAB on calcium mobilization (R-HSA-2730905 ) Nephrin interactions (R-HSA-373753 ) Costimulation by the CD28 family (R-HSA-388841 ) CD28 dependent PI3K/Akt signaling (R-HSA-389357 ) G beta (R-HSA-392451 ) G alpha (q) signalling events (R-HSA-416476 ) G alpha (12/13) signalling events (R-HSA-416482 ) VEGFA-VEGFR2 Pathway (R-HSA-4420097 ) Interleukin-3, 5 and GM-CSF signaling (R-HSA-512988 ) Constitutive Signaling by EGFRvIII (R-HSA-5637810 ) PI-3K cascade (R-HSA-5654689 ) PI-3K cascade (R-HSA-5654695 ) PI-3K cascade (R-HSA-5654710 ) PI-3K cascade (R-HSA-5654720 ) Interleukin receptor SHC signaling (R-HSA-912526 ) Regulation of signaling by CBL (R-HSA-912631 ) PI3K Cascade (R-HSA-109704 )
BioCyc Pathway	MetaCyc:HS02818-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

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2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bay 80-6946	DMLOS5R	Follicular lymphoma	2A80	Approved	[2]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[1]
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33 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[3]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[4]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[4]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[5], [6]
BEZ235	DMKBRDL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[7]
CLR-1404	DMAW4EL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
GDC-0077	DMY6WUV	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
GDC-0084	DMA9SEY	Glioblastoma of brain	2A00.00	Phase 2	[9]
GDC-0980/RG7422	DMF3MV1	Non-hodgkin lymphoma	2B33.5	Phase 2	[10]
GDC0941	DM1YAK6	Breast cancer	2C60-2C65	Phase 2	[3], [11]
IPI-549	DMG5Q7F	Bladder cancer	2C94	Phase 2	[4], [12]
PF-04691502	DMS610L	Endometrial cancer	2C76	Phase 2	[13]
PF-05212384	DMBL3VD	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[8]
PX-866	DMYISJK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[15], [16]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[17], [18]
Xl147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[15], [19]
BGT226	DMXKDUL	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[20]
CLR-1401	DM2FSM5	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]
CLR457	DM64FY7	Advanced solid tumour	2A00-2F9Z	Phase 1/2	[21]
CUDC-907	DMHIQDC	Acute myelogenous leukaemia	2A41	Phase 1/2	[22]
PA-799	DMLSYJQ	Colorectal cancer	2B91.Z	Phase 1/2	[23]
TG100-115	DMON4IL	Angioedema	4A00.15	Phase 1/2	[24], [25], [26]
AZD8186	DMWYF1H	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
DS-7423	DMCFJM3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[27]
GSK2126458	DMM7ZXR	Lymphoma	2A80-2A86	Phase 1	[28]
KA2237	DMFKEVO	B-cell lymphoma	2A86	Phase 1	[4]
LY294002	DMY1AFS	Neuroblastoma	2D11.2	Phase 1	[29], [30]
P-7170	DMIYQEM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
Perifosine	DMVYRH2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[31]
VS-5584	DMMO3G5	Malignant mesothelioma	2C26.0	Phase 1	[32]
ZSTK474	DMVIMQX	Solid tumour/cancer	2A00-2F9Z	Phase 1	[33]
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⏷ Show the Full List of 33 Clinical Trial Drug(s)

5 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adyvia	DMZ7WKN	Type-2 diabetes	5A11	Discontinued in Phase 2	[34]
GSK1059615	DMI6KQM	Breast cancer	2C60-2C65	Discontinued in Phase 1	[3]
PX-867	DMCNE2G	Cardiovascular disease	BA00-BE2Z	Terminated	[35]
SCR-44001	DMFZNUA	Solid tumour/cancer	2A00-2F9Z	Terminated	[36]
Wortmannin	DM8EVK5	Haematological malignancy	2B33.Y	Terminated	[37], [38], [11]
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27 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)phenol	DM54MDH	Discovery agent	N.A.	Investigative	[39]
5-QUINOXALIN-6-YLMETHYLENE-THIAZOLIDINE-2,4-DIONE	DMVX063	Discovery agent	N.A.	Investigative	[40]
AEZS-126	DMM52FD	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
AS-604850	DM9IUSM	Discovery agent	N.A.	Investigative	[41]
BAG956	DMWC34B	Haematological malignancy	2B33.Y	Investigative	[11]
CU-906	DMY1WEM	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
CZC 24832	DMLBYFG	Discovery agent	N.A.	Investigative	[42]
CZC-19091	DMYBL5G	Inflammation	1A00-CA43.1	Investigative	[15]
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate	DM3FH02	Discovery agent	N.A.	Investigative	[43]
Her2- and PSA-targeted TGX-D1	DM0VC84	Prostate cancer	2C82.0	Investigative	[44]
HM-5016699	DMKHVUE	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
HS-173	DM0A2UF	Discovery agent	N.A.	Investigative	[45]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[46]
LOR-220	DM71BIC	Bacterial infection	1A00-1C4Z	Investigative	[8]
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[43]
Multiform PI3K inhibitors	DMW2Z4I	Inflammation	1A00-CA43.1	Investigative	[8]
Myricetin	DMTV4L0	Discovery agent	N.A.	Investigative	[30]
P-6915	DMJDI7O	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
PF-03772304	DMJ0936	Solid tumour/cancer	2A00-2F9Z	Investigative	[47]
PF-4989216	DMSG6F1	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
PI-103	DMEK4TJ	Haematological malignancy	2B33.Y	Investigative	[11]
PI-3065	DMCQUWI	Discovery agent	N.A.	Investigative	[48]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[39]
PKI-402	DM6NX4H	Solid tumour/cancer	2A00-2F9Z	Investigative	[49]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[50]
TGX-221	DMM0LRE	Discovery agent	N.A.	Investigative	[51]
WX-037	DM6J7OQ	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
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⏷ Show the Full List of 27 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	1.67E-01	0.25	0.73
Breast cancer	2C82	Breast tissue	1.16E-01	-0.17	-0.49
Uterine cancer	2C82	Endometrium tissue	9.64E-01	-0.07	-0.3
Type 2 diabetes	5A11	Liver tissue	1.98E-01	-0.05	-0.55
Multiple myeloma	2C82	Bone marrow	2.69E-02	0.17	0.58
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References

1	PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
2	BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
3	Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
4	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5	Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
6	Phase I study of Rigosertib, an inhibitor of the phosphatidylinositol 3-kinase and Polo-like kinase 1 pathways, combined with gemcitabine in patients with solid tumors and pancreatic cancer.Clin Cancer Res.2012 Apr 1;18(7):2048-55.
7	The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses. Neoplasia. 2012 Jan;14(1):34-43.
8	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2155).
9	Current clinical development of PI3K pathway inhibitors in glioblastoma. Neuro Oncol. 2012 July; 14(7): 819-829.
10	GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36.
11	The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9.
12	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
13	PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity.Mol Cancer Ther.2011 Nov;10(11):2189-99.
14	First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.
15	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2156).
16	Clinical pipeline report, company report or official report of Sanofi Oncology.
17	An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.Cancer Chemother Pharmacol.2013 Apr;71(4):867-81.
18	Pan-PI-3 kinase inhibitor SF1126 shows antitumor and antiangiogenic activity in renal cell carcinoma.Cancer Chemother Pharmacol. 2015 Mar;75(3):595-608.
19	The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models.Mol Cancer Ther.2015 Apr;14(4):931-40.
20	Simultaneous targeting of PI3K and mTOR with NVP-BGT226 is highly effective in multiple myeloma. Anticancer Drugs. 2012 Jan;23(1):131-8.
21	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
22	Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling.Clin Cancer Res.2012 Aug 1;18(15):4104-13.
23	Company report (Chugai-pharm)
24	Aerosolized phosphoinositide 3-kinase gamma/delta inhibitor TG100-115 [3-[2,4-diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol] as a therapeutic can... J Pharmacol Exp Ther. 2009 Mar;328(3):758-65.
25	Isoform-selective PI3K inhibitors as novel therapeutics for the treatment of acute myocardial infarction. Biochem Soc Trans. 2007 Apr;35(Pt 2):204-6.
26	PI3Kgamma inhibition: towards an 'aspirin of the 21st century' Nat Rev Drug Discov. 2006 Nov;5(11):903-18.
27	Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423. PLoS One. 2014 Feb 4;9(2):e87220.
28	Company report (GSK)
29	Clinical pipeline report, company report or official report of Genentech (2009).
30	How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
31	Company report (Aezsinc)
32	VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther. 2013 Feb;12(2):151-61.
33	Combination of the PI3K inhibitor ZSTK474 with a PSMA-targeted immunotoxin accelerates apoptosis and regression of prostate cancer. Neoplasia. 2013 Oct;15(10):1172-83.
34	Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat.Am J Physiol Endocrinol Metab.2004 Sep;287(3):E463-71.
35	Pharmacologic profiling of phosphoinositide 3-kinase inhibitors as mitigators of ionizing radiation-induced cell death. J Pharmacol Exp Ther. 2013 Dec;347(3):669-80.
36	Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. PLoS One. 2010 Sep 24;5(9):e12965.
37	Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular endothelium to ionizing radiation. Cancer Res. 2002 Aug 15;62(16):4671-7.
38	Estrogen regulation of c-fos gene expression through phosphatidylinositol-3-kinase-dependent activation of serum response factor in MCF-7 breast cancer cells. Biochem Biophys Res Commun. 2002 Jun 7;294(2):384-94.
39	Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors. Bioorg Med Chem. 2007 Sep 1;15(17):5837-44.
40	The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
41	Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med. 2005 Sep;11(9):936-43.
42	A selective inhibitor reveals PI3Kgamma dependence of T(H)17 cell differentiation. Nat Chem Biol. 2012 Apr 29;8(6):576-82.
43	LY294002-geldanamycin heterodimers as selective inhibitors of the PI3K and PI3K-related family. Bioorg Med Chem Lett. 2001 Apr 9;11(7):909-13.
44	Development of a peptide-drug conjugate for prostate cancer therapy. Mol Pharm. 2011 Jun 6;8(3):901-12.
45	Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-kinase signaling and angiogenesis. J Med Chem. 2011 Apr 14;54(7):2455-66.
46	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. 2013 Aug 22;56(16):6386-401.
47	Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. ACS Med Chem Lett. 2012 Nov 7;4(1):91-7.
48	Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11.
49	Lead optimization of N-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: di... J Med Chem. 2010 Jan 28;53(2):798-810.
50	Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
51	PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med. 2005 May;11(5):507-14.