PDBsum entry: 2a4z

Transferase

PDB-id

2a4z

Contents

Description

Header details

Protein chain

Ligands

BYM

Waters ×7

* Residue conservation analysis

Tools

Image Generation

AstexViewer™@PDBe

Run PROCHECK

Clefts Calculation

PDB id:

2a4z

Name:

Transferase

Title:

Crystal structure of human pi3kgamma complexed with as604850

Structure:

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, gamma isoform. Chain: a. Fragment: p110 subunit gamma, residues 143-1101. Synonym: phosphatidylinositol 3-kinase catalytic subunit, pi3-kinase p110 subunit gamma, ptdins- 3-kinase p110, pi3k, pi3kgamma. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: sf9. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

UniProt:

P48736 (PK3CG_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

1102 a.a.

Struc:

812 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Enzyme class:

E.C.2.7.1.153 [IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate (see diagram below)

Pathway:

1-Phosphatidyl-myo-inositol Metabolism

Resolution:

2.90Å

R-factor:

0.264

R-free:

0.352

Authors:

M.Camps,T.Ruckle,H.Ji,V.Ardissone,F.Rintelen,J.Shaw, C.Ferrandi,C.Chabert,C.Gillieron,B.Francon,T.Martin, D.Gretener,D.Perrin,D.Leroy,P.-A.Vitte,E.Hirsch,M.P.Wymann, R.Cirillo,M.K.Schwarz,C.Rommel

Key ref:

M.Camps et al. (2005). Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis.. Nat Med, 11, 936-943. [PubMed id: 16127437] [DOI: 10.1038/nm1284]

Date:

30-Jun-05

Release date:

20-Sep-05

Related entries:

1e7u
1e7v
1e8w
1e8x
1e8y
2a5u

Quick_links

RCSB

PDBe

SRS

MMDB

JenaLib

OCA

PDBWiki

Proteopedia

CATH

SCOP

FSSP

HSSP

PDBSWS

PDBbind

PQS

PROCOGNATE

ProSAT

Whatcheck

EDS

Procheck

Clefts

Surface

Enzyme reaction for E.C.2.7.1.153

ATP	+	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate	=	ADP	+	1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site.

Key reference

DOI no: 10.1038/nm1284 Nat Med 11:936-943 (2005)

PubMed id: 16127437

Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis.

M.Camps, T.Rückle, H.Ji, V.Ardissone, F.Rintelen, J.Shaw, C.Ferrandi, C.Chabert, C.Gillieron, B.Françon, T.Martin, D.Gretener, D.Perrin, D.Leroy, P.A.Vitte, E.Hirsch, M.P.Wymann, R.Cirillo, M.K.Schwarz, C.Rommel.

ABSTRACT

Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lack of specificity, isoform selectivity and poor biopharmaceutical profile of PI3K inhibitors have so far hampered rigorous disease-relevant target validation. Here we describe the identification and development of specific, selective and orally active small-molecule inhibitors of PI3Kgamma (encoded by Pik3cg). We show that Pik3cg(-/-) mice are largely protected in mouse models of rheumatoid arthritis; this protection correlates with defective neutrophil migration, further validating PI3Kgamma as a therapeutic target. We also describe that oral treatment with a PI3Kgamma inhibitor suppresses the progression of joint inflammation and damage in two distinct mouse models of rheumatoid arthritis, reproducing the protective effects shown by Pik3cg(-/-) mice. Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Selected figure(s)

Figure 3.
Figure 3. Effects of PI3K gamma inhibitors on in vitro and in vivo chemotaxis. Figure 4.
Figure 4. Elimination of PI3K gamma function largely protects against CII-IA. (a) Mean paw thickness in Pik3cg-/- and Pik3cg+/+ mice after CII-IA induction. Data (n 5) are representative of two independent experiments. (b) H&E (synovial inflammation, original magnification, 50; neutrophils, original magnification, 1,000) - or safranin O (cartilage erosion, original magnification, 100) -stained representative joint sections from experiment shown in a, and sham-treated Pik3cg+/+ mice. Arrowheads indicate areas shown at higher magnification in the neutrophil column. Arrows point to neutrophils. (c) Histological scores of inflammation and cartilage erosion from the experiment shown in a. (d) Neutrophil infiltration in joint sections from experiment shown in a. Data are expressed as percentage of neutrophils from total number of cells. (e) CII-IA development represented as mean paw thickness in Pik3cg+/+ mice treated with vehicle or AS-605240 (n 5). Double arrow indicates initiation of the treatment. (f) H&E (original magnification, 50) - and safranin O (original magnification, 100) -stained representative joint sections from experiment shown in e. (g) Histological scores of synovial inflammation and cartilage erosion from the experiment shown in e. Data are mean s.e.m. * P < 0.05, ** P < 0.01, *** P < 0.001. Dotted line indicates mean paw thickness level in healthy animals.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Med (2005, 11, 936-943) copyright 2005.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id Reference

20081827 A.Berndt, S.Miller, O.Williams, D.D.Le, B.T.Houseman, J.I.Pacold, F.Gorrec, W.C.Hon, Y.Liu, C.Rommel, P.Gaillard, T.Rückle, M.K.Schwarz, K.M.Shokat, J.P.Shaw, and R.L.Williams (2010).
The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Nat Chem Biol, 6, 117-124.

PDB codes: 2wxe 2wxf 2wxg 2wxh 2wxi 2wxj 2wxk 2wxl 2wxm 2wxn 2wxo 2wxp 2wxq 2wxr 2x38

19907415 A.Schreiber, S.Rolle, L.Peripelittchenko, J.Rademann, W.Schneider, F.C.Luft, and R.Kettritz (2010).
Phosphoinositol 3-kinase-gamma mediates antineutrophil cytoplasmic autoantibody-induced glomerulonephritis.

Kidney Int, 77, 118-128.

19622728 A.Di Lorenzo, C.Fernández-Hernando, G.Cirino, and W.C.Sessa (2009).
Akt1 is critical for acute inflammation and histamine-mediated vascular leakage.

Proc Natl Acad Sci U S A, 106, 14552-14557.

19906996 B.Kurig, A.Shymanets, T.Bohnacker, Prajwal, C.Brock, M.R.Ahmadian, M.Schaefer, A.Gohla, C.Harteneck, M.P.Wymann, E.Jeanclos, and B.Nürnberg (2009).
Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110gamma.

Proc Natl Acad Sci U S A, 106, 20312-20317.

19137016 C.Guo, A.V.Gasparian, Z.Zhuang, D.A.Bosykh, A.A.Komar, A.V.Gudkov, and K.V.Gurova (2009).
9-Aminoacridine-based anticancer drugs target the PI3K/AKT/mTOR, NF-kappaB and p53 pathways.

Oncogene, 28, 1151-1161.

19182393 D.Kong, S.Yaguchi, and T.Yamori (2009).
Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA-dependent protein kinase.

Biol Pharm Bull, 32, 297-300.

19038971 F.Morello, A.Perino, and E.Hirsch (2009).
Phosphoinositide 3-kinase signalling in the vascular system.

Cardiovasc Res, 82, 261-271.

19248109 G.Palmer, D.Talabot-Ayer, C.Lamacchia, D.Toy, C.A.Seemayer, S.Viatte, A.Finckh, D.E.Smith, and C.Gabay (2009).
Inhibition of interleukin-33 signaling attenuates the severity of experimental arthritis.

Arthritis Rheum, 60, 738-749.

19255141 J.Gavard, X.Hou, Y.Qu, A.Masedunskas, D.Martin, R.Weigert, X.Li, and J.S.Gutkind (2009).
A role for a CXCR2/phosphatidylinositol 3-kinase gamma signaling axis in acute and chronic vascular permeability.

Mol Cell Biol, 29, 2469-2480.

19232066 J.M.Waldburger, and G.S.Firestein (2009).
Garden of therapeutic delights: new targets in rheumatic diseases.

Arthritis Res Ther, 11, 206.

19139077 L.M.Sly, M.J.Hamilton, E.Kuroda, V.W.Ho, F.L.Antignano, S.L.Omeis, C.J.van Netten-Thomas, D.Wong, H.K.Brugger, O.Williams, M.E.Feldman, B.T.Houseman, D.Fiedler, K.M.Shokat, and G.Krystal (2009).
SHIP prevents lipopolysaccharide from triggering an antiviral response in mice.

Blood, 113, 2945-2954.

19384329 L.Pallan, C.O.Savage, and L.Harper (2009).
ANCA-associated vasculitis: from bench research to novel treatments.

Nat Rev Nephrol, 5, 278-286.

19644878 L.Stangenberg, C.Ellson, V.Cortez-Retamozo, A.Ortiz-Lopez, H.Yuan, J.Blois, R.A.Smith, M.B.Yaffe, R.Weissleder, C.Benoist, D.Mathis, L.Josephson, and U.Mahmood (2009).
Abrogation of antibody-induced arthritis in mice by a self-activating viridin prodrug and association with impaired neutrophil and endothelial cell function.

Arthritis Rheum, 60, 2314-2324.

19454011 N.Butoescu, C.A.Seemayer, G.Palmer, P.A.Guerne, C.Gabay, E.Doelker, and O.Jordan (2009).
Magnetically retainable microparticles for drug delivery to the joint: efficacy studies in an antigen-induced arthritis model in mice.

Arthritis Res Ther, 11, R72.

19233845 R.P.Gobert, M.van den Eijnden, C.Szyndralewiez, C.Jorand-Lebrun, D.Swinnen, L.Chen, C.Gillieron, F.Pixley, P.Juillard, P.Gerber, C.Johnson-Léger, S.Halazy, M.Camps, A.Bombrun, M.Shipp, P.A.Vitte, V.Ardissone, C.Ferrandi, D.Perrin, C.Rommel, and R.H.van Huijsduijnen (2009).
GLEPP1/Protein-tyrosine Phosphatase {phi} Inhibitors Block Chemotaxis in Vitro and in Vivo and Improve Murine Ulcerative Colitis.

J Biol Chem, 284, 11385-11395.

19168509 S.Heymans, E.Hirsch, S.D.Anker, P.Aukrust, J.L.Balligand, J.W.Cohen-Tervaert, H.Drexler, G.Filippatos, S.B.Felix, L.Gullestad, D.Hilfiker-Kleiner, S.Janssens, R.Latini, G.Neubauer, W.J.Paulus, B.Pieske, P.Ponikowski, B.Schroen, H.P.Schultheiss, C.Tschöpe, M.Van Bilsen, F.Zannad, J.McMurray, and A.M.Shah (2009).
Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail, 11, 119-129.

19794881 S.Taouji, S.Dahan, R.Bossé, and E.Chevet (2009).
Current Screens Based on the AlphaScreen Technology for Deciphering Cell Signalling Pathways.

Curr Genomics, 10, 93.

19225663 T.J.Sundstrom, A.C.Anderson, and D.L.Wright (2009).
Inhibitors of phosphoinositide-3-kinase: a structure-based approach to understanding potency and selectivity.

Org Biomol Chem, 7, 840-850.

18383341 A.C.de Oliveira, E.Candelario-Jalil, H.S.Bhatia, K.Lieb, M.Hüll, and B.L.Fiebich (2008).
Regulation of prostaglandin E2 synthase expression in activated primary rat microglia: evidence for uncoupled regulation of mPGES-1 and COX-2.

Glia, 56, 844-855.

17998941 A.Denley, S.Kang, U.Karst, and P.K.Vogt (2008).
Oncogenic signaling of class I PI3K isoforms.

Oncogene, 27, 2561-2574.

17883327 A.Viola, and A.D.Luster (2008).
Chemokines and their receptors: drug targets in immunity and inflammation.

Annu Rev Pharmacol Toxicol, 48, 171-197.

18227218 C.Guiducci, C.Ghirelli, M.A.Marloie-Provost, T.Matray, R.L.Coffman, Y.J.Liu, F.J.Barrat, and V.Soumelis (2008).
PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation.

J Exp Med, 205, 315-322.

18711436 C.R.Mackay (2008).
Moving targets: cell migration inhibitors as new anti-inflammatory therapies.

Nat Immunol, 9, 988-998.

18332138 G.J.Litherland, C.Dixon, R.L.Lakey, T.Robson, D.Jones, D.A.Young, T.E.Cawston, and A.D.Rowan (2008).
Synergistic collagenase expression and cartilage collagenolysis are phosphatidylinositol 3-kinase/Akt signaling-dependent.

J Biol Chem, 283, 14221-14229.

18046317 H.Kuwana, Y.Terada, T.Kobayashi, T.Okado, J.M.Penninger, J.Irie-Sasaki, T.Sasaki, and S.Sasaki (2008).
The phosphoinositide-3 kinase gamma-Akt pathway mediates renal tubular injury in cisplatin nephrotoxicity.

Kidney Int, 73, 430-445.

18085662 H.Ohno, Y.Uemura, H.Murooka, H.Takanashi, T.Tokieda, Y.Ohzeki, K.Kubo, and I.Serizawa (2008).
The orally-active and selective c-Fms tyrosine kinase inhibitor Ki20227 inhibits disease progression in a collagen-induced arthritis mouse model.

Eur J Immunol, 38, 283-291.

18658026 J.Barbi, H.E.Cummings, B.Lu, S.Oghumu, T.Rückle, C.Rommel, W.Lafuse, C.C.Whitacre, and A.R.Satoskar (2008).
PI3Kgamma (PI3Kgamma) is essential for efficient induction of CXCR3 on activated T cells.

Blood, 112, 3048-3051.

18544649 J.Guillermet-Guibert, K.Bjorklof, A.Salpekar, C.Gonella, F.Ramadani, A.Bilancio, S.Meek, A.J.Smith, K.Okkenhaug, and B.Vanhaesebroeck (2008).
The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma.

Proc Natl Acad Sci U S A, 105, 8292-8297.

18662984 J.Sai, D.Raman, Y.Liu, J.Wikswo, and A.Richmond (2008).
Parallel phosphatidylinositol 3-kinase (PI3K)-dependent and Src-dependent pathways lead to CXCL8-mediated Rac2 activation and chemotaxis.

J Biol Chem, 283, 26538-26547.

18250464 K.Ali, M.Camps, W.P.Pearce, H.Ji, T.Rückle, N.Kuehn, C.Pasquali, C.Chabert, C.Rommel, and B.Vanhaesebroeck (2008).
Isoform-Specific Functions of Phosphoinositide 3-Kinases: p110{delta} but Not p110{gamma} Promotes Optimal Allergic Responses In Vivo.

J Immunol, 180, 2538-2544.

19029450 L.Zitvogel, and G.Kroemer (2008).
The dilemma of anticancer therapy: tumor-specific versus immune effects.

Blood, 112, 4364-4365.

18216772 M.P.Wymann, and R.Schneiter (2008).
Lipid signalling in disease.

Nat Rev Mol Cell Biol, 9, 162-176.

18523230 M.S.Thomas, J.S.Mitchell, C.C.DeNucci, A.L.Martin, and Y.Shimizu (2008).
The p110gamma isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites.

J Leukoc Biol, 84, 814-823.

18711433 P.Friedl, and B.Weigelin (2008).
Interstitial leukocyte migration and immune function.

Nat Immunol, 9, 960-969.

18820032 Q.Lai Kwan Lam, O.King Hung Ko, B.J.Zheng, and L.Lu (2008).
Local BAFF gene silencing suppresses Th17-cell generation and ameliorates autoimmune arthritis.

Proc Natl Acad Sci U S A, 105, 14993-14998.

19568798 R.M.Gunn, and H.C.Hailes (2008).
Insights into the PI3-K-PKB-mTOR signalling pathway from small molecules.

J Chem Biol, 1, 49-62.

18596232 S.Chen, F.Lin, M.E.Shin, F.Wang, L.Shen, and H.E.Hamm (2008).
RACK1 regulates directional cell migration by acting on G betagamma at the interface with its effectors PLC beta and PI3K gamma.

Mol Biol Cell, 19, 3909-3922.

18509048 S.Sauer, L.Bruno, A.Hertweck, D.Finlay, M.Leleu, M.Spivakov, Z.A.Knight, B.S.Cobb, D.Cantrell, E.O'Connor, K.M.Shokat, A.G.Fisher, and M.Merkenschlager (2008).
T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR.

Proc Natl Acad Sci U S A, 105, 7797-7802.

18412166 T.M.Randis, K.D.Puri, H.Zhou, and T.G.Diacovo (2008).
Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils.

Eur J Immunol, 38, 1215-1224.

18587386 Y.Aikawa, K.Morimoto, T.Yamamoto, H.Chaki, A.Hashiramoto, H.Narita, S.Hirono, and S.Shiozawa (2008).
Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1.

Nat Biotechnol, 26, 817-823.

19384426 A.Arcaro, and A.S.Guerreiro (2007).
The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications.

Curr Genomics, 8, 271-306.

17501698 A.F.Hezel, and D.P.Ryan (2007).
Emerging therapies for colorectal cancer.

Expert Opin Investig Drugs, 16, 867-876.

17290298 C.Rommel, M.Camps, and H.Ji (2007).
PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond?

Nat Rev Immunol, 7, 191-201.

17614878 D.A.Medina-Tato, S.G.Ward, and M.L.Watson (2007).
Phosphoinositide 3-kinase signalling in lung disease: leucocytes and beyond.

Immunology, 121, 448-461.

17711503 D.Kong, and T.Yamori (2007).
ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms.

Cancer Sci, 98, 1638-1642.

17626838 H.Ji, F.Rintelen, C.Waltzinger, D.Bertschy Meier, A.Bilancio, W.Pearce, E.Hirsch, M.P.Wymann, T.Rückle, M.Camps, B.Vanhaesebroeck, K.Okkenhaug, and C.Rommel (2007).
Inactivation of PI3Kgamma and PI3Kdelta distorts T-cell development and causes multiple organ inflammation.

Blood, 110, 2940-2947.

17164340 J.A.Deane, M.G.Kharas, J.S.Oak, L.N.Stiles, J.Luo, T.I.Moore, H.Ji, C.Rommel, L.C.Cantley, T.E.Lane, and D.A.Fruman (2007).
T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling.

Blood, 109, 2894-2902.

17483449 J.D.Chang, G.K.Sukhova, P.Libby, E.Schvartz, A.H.Lichtenstein, S.J.Field, C.Kennedy, S.Madhavarapu, J.Luo, D.Wu, and L.C.Cantley (2007).
Deletion of the phosphoinositide 3-kinase p110gamma gene attenuates murine atherosclerosis.

Proc Natl Acad Sci U S A, 104, 8077-8082.

17530707 M.A.Amin, P.J.Mansfield, A.Pakozdi, P.L.Campbell, S.Ahmed, R.J.Martinez, and A.E.Koch (2007).
Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways.

Arthritis Rheum, 56, 1787-1797.

17635796 M.Bokarewa, A.Tarkowski, and M.Magnusson (2007).
Pathological survivin expression links viral infections with pathogenesis of erosive rheumatoid arthritis.

Scand J Immunol, 66, 192-198.

17644738 N.Kim, A.Saudemont, L.Webb, M.Camps, T.Ruckle, E.Hirsch, M.Turner, and F.Colucci (2007).
The p110delta catalytic isoform of PI3K is a key player in NK-cell development and cytokine secretion.

Blood, 110, 3202-3208.

17984576 N.Tamura, and K.Haruta (2007).
[Therapeutic potential of phosphoinositide 3-kinase inhibitors in rheumatoid arthritis]

Nihon Rinsho Meneki Gakkai Kaishi, 30, 369-374.

17916723 P.T.Hawkins, and L.R.Stephens (2007).
PI3Kgamma is a key regulator of inflammatory responses and cardiovascular homeostasis.

Science, 318, 64-66.

17968336 S.E.Sweeney, and G.S.Firestein (2007).
Primer: signal transduction in rheumatic disease--a clinician's guide.

Nat Clin Pract Rheumatol, 3, 651-660.

17827385 S.Kim, A.Garcia, S.P.Jackson, and S.P.Kunapuli (2007).
Insulin-like growth factor-1 regulates platelet activation through PI3-Kalpha isoform.

Blood, 110, 4206-4213.

17963503 S.Shahrara, H.P.Castro-Rueda, G.K.Haines, and A.E.Koch (2007).
Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues.

Arthritis Res Ther, 9, R112.

16702948 C.Billottet, V.L.Grandage, R.E.Gale, A.Quattropani, C.Rommel, B.Vanhaesebroeck, and A.Khwaja (2006).
A selective inhibitor of the p110delta isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16.

Oncogene, 25, 6648-6659.

16823479 C.F.Semenkovich (2006).
Insulin resistance and atherosclerosis.

J Clin Invest, 116, 1813-1822.

16680006 D.L.Williams, T.Ozment-Skelton, and C.Li (2006).
Modulation of the phosphoinositide 3-kinase signaling pathway alters host response to sepsis, inflammation, and ischemia/reperfusion injury.

Shock, 25, 432-439.

17172449 J.Doukas, W.Wrasidlo, G.Noronha, E.Dneprovskaia, R.Fine, S.Weis, J.Hood, A.Demaria, R.Soll, and D.Cheresh (2006).
Phosphoinositide 3-kinase gamma/delta inhibition limits infarct size after myocardial ischemia/reperfusion injury.

Proc Natl Acad Sci U S A, 103, 19866-19871.

16732722 M.Braddock, and C.Murray (2006).
10th anniversary Inflammation and Immune Diseases Drug Discovery and Development Summit. 20-21 March 2006, New Brunswick, USA.

Expert Opin Investig Drugs, 15, 721-727.

16924470 R.Hooft van Huijsduijnen, and C.Rommel (2006).
Decompartmentalizing target validation-thinking outside the pipeline boxes.

J Mol Med, 84, 802-813.

17080027 T.Rückle, M.K.Schwarz, and C.Rommel (2006).
PI3Kgamma inhibition: towards an 'aspirin of the 21st century'?

Nat Rev Drug Discov, 5, 903-918.

16127435 D.F.Barber, A.Bartolomé, C.Hernandez, J.M.Flores, C.Redondo, C.Fernandez-Arias, M.Camps, T.Rückle, M.K.Schwarz, S.Rodríguez, C.Martinez-A, D.Balomenos, C.Rommel, and A.C.Carrera (2005).
PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus.

Nat Med, 11, 933-935.

16145571 P.S.Ohashi, and J.R.Woodgett (2005).
Modulating autoimmunity: pick your PI3 kinase.

Nat Med, 11, 924-925.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.