Log in

Relevant bibliographies by topics / PI3K / Journal articles

To see the other types of publications on this topic, follow the link: PI3K.

Journal articles on the topic 'PI3K'

Author: Grafiati

Published: 4 June 2021

Last updated: 25 July 2025

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'PI3K.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Hus, Iwona, Bartosz Puła, and Tadeusz Robak. "PI3K Inhibitors for the Treatment of Chronic Lymphocytic Leukemia: Current Status and Future Perspectives." Cancers 14, no. 6 (2022): 1571. http://dx.doi.org/10.3390/cancers14061571.

Full text

Abstract:

Phosphoinositide 3-kinases (PI3Ks) signaling regulates key cellular processes, such as growth, survival and apoptosis. Among the three classes of PI3K, class I is the most important for the development, differentiation and activation of B and T cells. Four isoforms are distinguished within class I (PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ). PI3Kδ expression is limited mainly to the B cells and their precursors, and blocking PI3K has been found to promote apoptosis of chronic lymphocytic leukemia (CLL) cells. Idelalisib, a selective PI3Kδ inhibitor, was the first-in-class PI3Ki introduced into CLL treatme

APA, Harvard, Vancouver, ISO, and other styles

2

Bohat, Ritu, Xiaofang Liang, Chunyu Xu, et al. "Abstract 4444: Targeting PI3K isoforms to improve the effectiveness of T cell mediated immunotherapy." Cancer Research 83, no. 7_Supplement (2023): 4444. http://dx.doi.org/10.1158/1538-7445.am2023-4444.

Full text

Abstract:

Abstract Hyperactivation of the PI3K pathway has been reported to correlate with resistance to immune checkpoint blockade therapy (ICB) in melanoma, highlighting the therapeutic potential of combining PI3K inhibition (PI3Ki) with ICB. To maximize the clinical benefit of PI3Ki-based immune oncology (IO) combination, we characterized the role of PI3K isoforms in tumor and T cells and determined the immunological impacts of PI3Ki alone or in combination with ICB. Inhibitions of PI3K were achieved by either genetic knockdown (KD) or the bioactive compound in PTEN-present (B16/MC38), PTEN-absent (B

APA, Harvard, Vancouver, ISO, and other styles

3

Miller, Michelle, Philip Thompson, and Sandra Gabelli. "Structural Determinants of Isoform Selectivity in PI3K Inhibitors." Biomolecules 9, no. 3 (2019): 82. http://dx.doi.org/10.3390/biom9030082.

Full text

Abstract:

Phosphatidylinositol 3-kinases (PI3Ks) are important therapeutic targets for the treatment of cancer, thrombosis, and inflammatory and immune diseases. The four highly homologous Class I isoforms, PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ have unique, non-redundant physiological roles and as such, isoform selectivity has been a key consideration driving inhibitor design and development. In this review, we discuss the structural biology of PI3Ks and how our growing knowledge of structure has influenced the medicinal chemistry of PI3K inhibitors. We present an analysis of the available structure-selectivity

APA, Harvard, Vancouver, ISO, and other styles

4

Hawkins, P. T., K. E. Anderson, K. Davidson, and L. R. Stephens. "Signalling through Class I PI3Ks in mammalian cells." Biochemical Society Transactions 34, no. 5 (2006): 647–62. http://dx.doi.org/10.1042/bst0340647.

Full text

Abstract:

It is now accepted that activation of Class I PI3Ks (phosphoinositide 3-kinases) is one of the most important signal transduction pathways used by cell-surface receptors to control intracellular events. The receptors which access this pathway include those that recognize growth factors, hormones, antigens and inflammatory stimuli, and the cellular events known to be regulated include cell growth, survival, proliferation and movement. We have learnt a great deal about the family of Class I PI3K enzymes themselves and the structural adaptations which allow a variety of cell-surface receptors to

APA, Harvard, Vancouver, ISO, and other styles

5

Garcia, Analia, Soochong Kim, Kamala Bhavaraju, Simone M. Schoenwaelder та Satya P. Kunapuli. "Role of phosphoinositide 3-kinase β in platelet aggregation and thromboxane A2 generation mediated by Gi signalling pathways". Biochemical Journal 429, № 2 (2010): 369–77. http://dx.doi.org/10.1042/bj20100166.

Full text

Abstract:

PI3Ks (phosphoinositide 3-kinases) play a critical role in platelet functional responses. PI3Ks are activated upon P2Y12 receptor stimulation and generate pro-aggregatory signals. P2Y12 receptor has been shown to play a key role in the platelet aggregation and thromboxane A2 generation caused by co-stimulation with Gq or Gz, or super-stimulation of Gi pathways. In the present study, we evaluated the role of specific PI3K isoforms α, β, γ and δ in platelet aggregation, thromboxane A2 generation and ERK (extracellular-signal-regulated kinase) activation. Our results show that loss of the PI3K si

APA, Harvard, Vancouver, ISO, and other styles

6

Stypik, Mariola, Stanisław Michałek, Nina Orłowska та ін. "Design, Synthesis, and Development of Pyrazolo[1,5-a]pyrimidine Derivatives as a Novel Series of Selective PI3Kδ Inhibitors: Part II—Benzimidazole Derivatives". Pharmaceuticals 15, № 8 (2022): 927. http://dx.doi.org/10.3390/ph15080927.

Full text

Abstract:

Phosphoinositide 3-kinase (PI3K) is the family of lipid kinases participating in vital cellular processes such as cell proliferation, growth, migration, or cytokines production. Due to the high expression of these proteins in many human cells and their involvement in metabolism regulation, normal embryogenesis, or maintaining glucose homeostasis, the inhibition of PI3K (especially the first class which contains four subunits: α, β, γ, δ) is considered to be a promising therapeutic strategy for the treatment of inflammatory and autoimmune diseases such as systemic lupus erythematosus (SLE) or m

APA, Harvard, Vancouver, ISO, and other styles

7

Diacovo, Thomas, Dosh Whye, Evgeni Efimenko та ін. "Therapeutic Utility of PI3Kγ Inhibition in Leukemogenesis and Tumor Cell Survival". Blood 120, № 21 (2012): 1492. http://dx.doi.org/10.1182/blood.v120.21.1492.1492.

Full text

Abstract:

Abstract Abstract 1492 Aberrant activation of the PI3K/Akt signaling pathway is a frequent event in cancer including various types of leukemia. Consequently, much emphasis has been placed on developing inhibitors that target this pathway. However, this would require an in depth knowledge of the role that specific class I PI3K isoforms (α, β, γ, δ)play in the pathogenesis of a particular hematological malignancy. For instance, PI3Kδ has been shown to be essential for the growth and survival of tumors derived from B cells such as chronic lymphocytic leukemia (CLL). Such knowledge has lead to dev

APA, Harvard, Vancouver, ISO, and other styles

8

Wang, Bi-Dar, Alyssa Lucero, Siyoung Ha та Reyhaneh Yarmohammadi. "PI3Kδ as a Novel Therapeutic Target for Aggressive Prostate Cancer". Cancers 17, № 10 (2025): 1610. https://doi.org/10.3390/cancers17101610.

Full text

Abstract:

Phosphoinositide 3-kinases (PI3Ks) signaling represents an important pathway regulating cell proliferation, survival, invasion, migration, and metabolism. Notably, PI3K/AKT/mTOR signaling is frequently dysregulated in the majority of malignancies. Among the class IA PI3Ks (PI3Kα/β/δ), emerging evidence has implicated that PI3Kδ is not only overexpressed in leukocytes but also in solid tumors, including prostate cancer. The critical role of PI3Kδ in tumorigenesis and in the creation of a suppressive tumor microenvironment, along with the recent finding of PI3Kδ splice isoforms in promoting tumo

APA, Harvard, Vancouver, ISO, and other styles

9

Huang, Yi Elaine, Miho Iijima, Carole A. Parent, Satoru Funamoto, Richard A. Firtel, and Peter Devreotes. "Receptor-mediated Regulation of PI3Ks Confines PI(3,4,5)P3 to the Leading Edge of Chemotaxing Cells." Molecular Biology of the Cell 14, no. 5 (2003): 1913–22. http://dx.doi.org/10.1091/mbc.e02-10-0703.

Full text

Abstract:

Recent studies have demonstrated that PH domains specific for PI(3,4,5)P3 accumulate at the leading edge of a number of migrating cells and that PI3Ks and PTEN associate with the membrane at the front and back, respectively, of chemotaxing Dictyostelium discoideum cells. However, the dependence of chemoattractant induced changes in PI(3,4,5)P3 on PI3K and PTEN activities have not been defined. We find that bulk PI(3,4,5)P3 levels increase transiently upon chemoattractant stimulation, and the changes are greater and more prolonged in pten– cells. PI3K activation increases within 5 s of chemoatt

APA, Harvard, Vancouver, ISO, and other styles

10

Lin, Shu, Zuwen Zhou, Rui Tan та ін. "Abstract 5453: FCN-289, a novel, potent and selective PI3Kδ inhibitor for the treatment of B-cell malignancies". Cancer Research 82, № 12_Supplement (2022): 5453. http://dx.doi.org/10.1158/1538-7445.am2022-5453.

Full text

Abstract:

Abstract Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway plays critical roles in cell growth, differentiation, motility, survival, and intracellular trafficking, and is one of the most frequently dysregulated pathways in human cancers including B-cell malignancies. There are 3 classes of PI3K, among which Class I PI3Ks including PI3Kα, β, γ, and δ isoforms are the mostly studied and plays key roles in physiological functions. PI3Kα has a role in insulin-dependent signaling, PI3Kβ functions in platelet aggregation, thrombosis and insulin signaling, and PI3Kγ/δ are expressed mainly in leukocyt

APA, Harvard, Vancouver, ISO, and other styles

11

Tsolakos, N., T. N. Durrant, T. Chessa, et al. "Quantitation of class IA PI3Ks in mice reveals p110-free-p85s and isoform-selective subunit associations and recruitment to receptors." Proceedings of the National Academy of Sciences 115, no. 48 (2018): 12176–81. http://dx.doi.org/10.1073/pnas.1803446115.

Full text

Abstract:

Class IA PI3Ks have many roles in health and disease. The rules that govern intersubunit and receptor associations, however, remain unclear. We engineered mouse lines in which individual endogenous class IA PI3K subunits were C-terminally tagged with 17aa that could be biotinylated in vivo. Using these tools we quantified PI3K subunits in streptavidin or PDGFR pull-downs and cell lysates. This revealed that p85α and β bound equivalently to p110α or p110β but p85α bound preferentially to p110δ. p85s were found in molar-excess over p110s in a number of contexts including MEFs (p85β, 20%) and liv

APA, Harvard, Vancouver, ISO, and other styles

12

Wen, Hanning, Shuai Mao, Mahamadou Djibo та ін. "Abstract 3001: Highly selective and oral bioavailable PI3Kγ inhibitor for cancer immunotherapy by targeting myeloid-derived suppressor cells in tumor". Cancer Research 85, № 8_Supplement_1 (2025): 3001. https://doi.org/10.1158/1538-7445.am2025-3001.

Full text

Abstract:

Abstract Introduction: Phosphoinositide 3-kinases (PI3Ks) are crucial for cell growth, survival, and metabolism, with dysregulated signaling common in cancer. The PI3K family includes four isoforms—PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ—each with distinct roles, where pan-PI3K inhibition often results in toxicity due to broad isoform expression. Existing various PI3K isoform inhibitors, despite in vitro specificity, often act as pan-inhibitors at high in vivo clinical effective concentrations (1μ M to 5μ M). We developed a highly selective PI3Kγ inhibitor that retains its specificity even at therapeut

APA, Harvard, Vancouver, ISO, and other styles

13

Xia, Liang, Yan Zhang, Jingbo Zhang, et al. "Identification of Novel Thiazolo[5,4-b]Pyridine Derivatives as Potent Phosphoinositide 3-Kinase Inhibitors." Molecules 25, no. 20 (2020): 4630. http://dx.doi.org/10.3390/molecules25204630.

Full text

Abstract:

A series of novel 2-pyridyl, 4-morpholinyl substituted thiazolo[5,4-b]pyridine analogues have been designed and synthesized in this paper. These thiazolo[5,4-b]pyridines were efficiently prepared in seven steps from commercially available substances in moderate to good yields. All of these N-heterocyclic compounds were characterized by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) analysis and tested for phosphoinositide 3-kinase (PI3K) enzymatic assay. The results indicated that these N-heterocyclic compounds showed potent PI3K inhibitory activity, and the IC50

APA, Harvard, Vancouver, ISO, and other styles

14

Yang, Bing, Bo Zhang, Qun Zhao, Jin Li та Yujun Shi. "Development of New Thiophene-Containing Triaryl Pyrazoline Derivatives as PI3Kγ Inhibitors". Molecules 27, № 8 (2022): 2404. http://dx.doi.org/10.3390/molecules27082404.

Full text

Abstract:

A series of new thiophene-containing triaryl pyrazoline derivatives, 3a–3t, were synthesized and evaluated regarding PI3K inhibition activity and anti-tumor potency based on a trial of introducing significant moieties, including pyrazoline and thiophene, and simplifying the parallel ring structures. Most of the tested compounds indicated potent PI3K inhibitory potency, with this series of compounds showing more potency for PI3Kγ than PI3Kα. The top hit 3s seemed more potent than the positive control LY294002 on inhibiting PI3Kγ (IC50 values: 0.066 μM versus 0.777 μM) and more selective from PI

APA, Harvard, Vancouver, ISO, and other styles

15

Paul, Juliane, Maurice Sojoun, Antje M. Wengner та ін. "Simultaneous Inhibition of PI3Kδ and PI3Kα Induces ABC-DLBCL Regression Via Attenuation of BCR-Dependent and Independent Activation of NF-Kb and AKT". Blood 128, № 22 (2016): 1057. http://dx.doi.org/10.1182/blood.v128.22.1057.1057.

Full text

Abstract:

Abstract Introduction: ABC-DLBCL is a subtype of DLBCL with less favorable clinical outcomes to the standard of care (SoC) therapies. Constitutive activation of NF-κB by various genetic alterations in ABC-DLBCL has been identified as one of the key mechanisms driving chemotherapy resistance. Inhibition of B cell receptor (BCR) signaling with BTK (Bruton's tyrosine kinase) inhibitor ibrutinib demonstrated encouraging clinical responses in ABC-DLBCL. However, patients with CD79wt/MyD88mut, or CARD11mut did not respond to ibrutinib, indicating the need for new therapies targeting ibrutinib refrac

APA, Harvard, Vancouver, ISO, and other styles

16

Bresnick, Anne R., та Jonathan M. Backer. "PI3Kβ—A Versatile Transducer for GPCR, RTK, and Small GTPase Signaling". Endocrinology 160, № 3 (2019): 536–55. http://dx.doi.org/10.1210/en.2018-00843.

Full text

Abstract:

AbstractThe phosphoinositide 3-kinase (PI3K) family includes eight distinct catalytic subunits and seven regulatory subunits. Only two PI3Ks are directly regulated downstream from G protein–coupled receptors (GPCRs): the class I enzymes PI3Kβ and PI3Kγ. Both enzymes produce phosphatidylinositol 3,4,5-trisposphate in vivo and are regulated by both heterotrimeric G proteins and small GTPases from the Ras or Rho families. However, PI3Kβ is also regulated by direct interactions with receptor tyrosine kinases (RTKs) and their tyrosine phosphorylated substrates, and similar to the class II and III P

APA, Harvard, Vancouver, ISO, and other styles

17

Wright, Brock, Samuel King, and Cenk Suphioglu. "The Importance of Phosphoinositide 3-Kinase in Neuroinflammation." International Journal of Molecular Sciences 25, no. 21 (2024): 11638. http://dx.doi.org/10.3390/ijms252111638.

Full text

Abstract:

Neuroinflammation, characterised by the activation of immune cells in the central nervous system (CNS), plays a dual role in both protecting against and contributing to the progression of neurodegenerative diseases, such as Alzheimer’s disease (AD) and multiple sclerosis (MS). This review explores the role of phosphoinositide 3-kinase (PI3K), a key enzyme involved in cellular survival, proliferation, and inflammatory responses, within the context of neuroinflammation. Two PI3K isoforms of interest, PI3Kγ and PI3Kδ, are specific to the regulation of CNS cells, such as microglia, astrocytes, neu

APA, Harvard, Vancouver, ISO, and other styles

18

Arcucci, Silvia, Fernanda Ramos-Delgado, Coralie Cayron та ін. "Organismal roles for the PI3Kα and β isoforms: their specificity, redundancy or cooperation is context-dependent". Biochemical Journal 478, № 6 (2021): 1199–225. http://dx.doi.org/10.1042/bcj20210004.

Full text

Abstract:

PI3Ks are important lipid kinases that produce phosphoinositides phosphorylated in position 3 of the inositol ring. There are three classes of PI3Ks: class I PI3Ks produce PIP3 at plasma membrane level. Although D. melanogaster and C. elegans have only one form of class I PI3K, vertebrates have four class I PI3Ks called isoforms despite being encoded by four different genes. Hence, duplication of these genes coincides with the acquisition of coordinated multi-organ development. Of the class I PI3Ks, PI3Kα and PI3Kβ, encoded by PIK3CA and PIK3CB, are ubiquitously expressed. They present similar

APA, Harvard, Vancouver, ISO, and other styles

19

Narkhede, Mayur, and Bruce D. Cheson. "Copanlisib in the treatment of non-Hodgkin lymphoma." Future Oncology 16, no. 26 (2020): 1947–55. http://dx.doi.org/10.2217/fon-2020-0195.

Full text

Abstract:

B-cell receptor signaling is important in the pathogenesis of non-Hodgkin lymphoma. The PI3K pathway is activated by B-cell receptor signaling. Recently, several PI3K inhibitors have been in development for the treatment of indolent non-Hodgkin lymphomas. Copanlisib is a PI3Kα and PI3Kδ inhibitor that has been approved for its use as third-line therapy in the treatment of relapsed or refractory follicular lymphoma. The two other PI3k inhibitors approved by the US FDA in this setting are idelalisib and duvelisib. In this review, we compare the efficacy and adverse event profile of these differe

APA, Harvard, Vancouver, ISO, and other styles

20

Hutter, Grit, Yvonne Zimmermann, Anna-Katharina Zoellner, et al. "Combination of PI3K and PDPK1 Inhibitors Is Highly Effective in Mantle Cell Lymphoma." Blood 124, no. 21 (2014): 3123. http://dx.doi.org/10.1182/blood.v124.21.3123.3123.

Full text

Abstract:

Abstract Introduction: Mantle cell lymphoma (MCL), is a distinct lymphoma subtype with an aggressive clinical course and a median survival of 3-5 years. New emerging strategies include especially inhibitors of the PI3K/Akt/mTOR pathway which is constitutively activated in MCL and plays a critical role in tumor growth and survival. In the present study we analysed four different PI3K-Inhibitors (IPI-145, CAL101, A66 and TGX221) targeting different isoforms (PI3Kδ/γ, PI3Kδ, PI3Kα and PI3Kβ) for their effectiveness in MCL. Methods: MCL cell lines (Z-138, Mino-1, Granta-519, Jeko-1, Rec-1, Maver-1

APA, Harvard, Vancouver, ISO, and other styles

21

Barberis, Laura, та Emilio Hirsch. "Targeting phosphoinositide 3-kinase γ to fight inflammation and more". Thrombosis and Haemostasis 99, № 02 (2008): 279–85. http://dx.doi.org/10.1160/th07-10-0632.

Full text

Abstract:

SummaryThe family of class I phosphoinositide-3-kinase (PI3K) is composed of four lipid kinases involved at multiple levels in innate and adaptive immune responses. Class I PI3Ks are divided into two subclasses, IA and IB, sharing a similar catalytic core. Whereas class IA PI3Ks are primarily activated by receptor tyrosine kinases, the unique element of class IB PI3K (PI3Kγ) is activated by G protein coupled receptors (GPCRs), like chemokine receptors. PI3Kγ is mainly expressed in leukocytes where it plays a significant role in chemotaxis. Here, we report recent advances in the analysis of the

APA, Harvard, Vancouver, ISO, and other styles

22

Thijssen, Rachel, Gregor van Bochove, Martin FM de Rooij та ін. "Combined Inhibition of Phosphatidylinositol 3-Kinase (PI3K) Isoform α and δ By the Pan-Class I PI3K Inhibitor SAR245409 (XL765) in Primary Chronic Lymphocytic Leukemia Cells Blocks Survival, Adhesion and Proliferation". Blood 124, № 21 (2014): 4691. http://dx.doi.org/10.1182/blood.v124.21.4691.4691.

Full text

Abstract:

Abstract CLL cells are highly dependent on B- cell receptor (BCR) signaling and on stimuli from the microenvironment for survival and proliferation. New drugs targeting PI3K downstream of BCR signaling have emerged as promising treatment options for patients with CLL. Among four PI3K catalytic subunits, the PI3Kd isoform is crucial for downstream BCR signaling, but the relative importance of the PI3Kα isoform in CLL is less clear. Impressive clinical activity of idelalisib in CLL and indolent NHL patients was recently reported. Idelalisib, a PI3Kd specific inhibitor, inhibits chemotaxis and ad

APA, Harvard, Vancouver, ISO, and other styles

23

Figueiredo, Ana M., Pilar Villacampa, Rodrigo Diéguez-Hurtado, et al. "Phosphoinositide 3-Kinase–Regulated Pericyte Maturation Governs Vascular Remodeling." Circulation 142, no. 7 (2020): 688–704. http://dx.doi.org/10.1161/circulationaha.119.042354.

Full text

Abstract:

Background: Pericytes regulate vessel stabilization and function, and their loss is associated with diseases such as diabetic retinopathy or cancer. Despite their physiological importance, pericyte function and molecular regulation during angiogenesis remain poorly understood. Methods: To decipher the transcriptomic programs of pericytes during angiogenesis, we crossed Pdgfrb(BAC)-CreER T2 mice into RiboTag flox/flox mice. Pericyte morphological changes were assessed in mural cell-specific R26-mTmG reporter mice, in which low doses of tamoxifen allowed labeling of single-cell pericytes at high

APA, Harvard, Vancouver, ISO, and other styles

24

Meadows, Sarah, Sorensen Rick, Yahiaoui Anella, et al. "Up-Regulation of the PI3K Signaling Pathway Mediates Resistance to Idelalisib." Blood 126, no. 23 (2015): 3707. http://dx.doi.org/10.1182/blood.v126.23.3707.3707.

Full text

Abstract:

Abstract Background: Idelalisib (Zydelig®), a potent and selective PI3Kδ inhibitor, was recently approved for the treatment of relapsed CLL, SLL and FL. PI3Kδ is critical for malignant B-cell proliferation, survival and homing, and inhibition results in a rapid decrease in lymphadenopathy and clinical response (Yang et al., Clin Can Res 2015). Although idelalisib is very potent in mitigating disease, most patients experience incomplete response and ultimately progress. To understand the mechanism of resistance, we screened ABC-DLBCL cell lines for sensitivity to idelalisib and selected TMD8, a

APA, Harvard, Vancouver, ISO, and other styles

25

Newman, Debra K. "PI3Kβ goes to the head of its class". Blood 114, № 10 (2009): 2011–12. http://dx.doi.org/10.1182/blood-2009-06-228551.

Full text

Abstract:

Abstract In this issue of Blood, Canobbio and colleagues report on the unique and redundant contributions of 2 isoforms of PI3K, PI3Kβ and PI3Kγ, to platelet activation by GPCRs and ITAM–coupled receptors.1

APA, Harvard, Vancouver, ISO, and other styles

26

Yano, Naohiro, Vlad Ianus, Ting C. Zhao, Andy Tseng, James F. Padbury та Yi-Tang Tseng. "A novel signaling pathway for β-adrenergic receptor-mediated activation of phosphoinositide 3-kinase in H9c2 cardiomyocytes". American Journal of Physiology-Heart and Circulatory Physiology 293, № 1 (2007): H385—H393. http://dx.doi.org/10.1152/ajpheart.01318.2006.

Full text

Abstract:

Stimulation of cardiac β-adrenergic receptors (β-AR) activates both the Gs- and Gi-coupled signaling cascades, including the phosphoinositide 3 kinase (PI3K) pathway, that have important physiological implications. Multiple isoforms of PI3K exist in the heart. The goals of this study were to examine the intracellular signaling pathways linking β-AR to PI3K and to identify the PI3K isoform mediating this transactivation in a cardiac context. Acute β-AR stimulation with isoproterenol resulted in increased tyrosine kinase-associated PI3K activity and phosphorylation of Akt and p70S6K in H9c2 card

APA, Harvard, Vancouver, ISO, and other styles

27

Perez-Stable, Carlos, Alicia de las Pozas, Medhi Wangpaichitr, et al. "Growth Hormone-Releasing Hormone (GHRH) Antagonist Peptides Combined with PI3K Isoform Inhibitors Enhance Cell Death in Prostate Cancer." Cancers 17, no. 10 (2025): 1643. https://doi.org/10.3390/cancers17101643.

Full text

Abstract:

Background. Antagonists of GHRH have experimental therapeutic value, but as single agents are not likely to improve clinical outcomes, especially in advanced prostate cancer resistant to androgen deprivation therapy. Our objective is to identify anti-cancer drugs that, in combination with MIA-602 or -690 GHRH antagonists, increase cell death in all types of prostate cancer. Methods/Results. We identified inhibitors of PI3Kα or PI3Kβ that consistently increased cell death when combined with MIA-602/690. The PI3K family is critical in mediating upstream signals from receptors to downstream AKT/m

APA, Harvard, Vancouver, ISO, and other styles

28

RUBIO, Ignacio, Pablo RODRIGUEZ-VICIANA, Julian DOWNWARD та Reinhard WETZKER. "Interaction of Ras with phosphoinositide 3-kinase γ". Biochemical Journal 326, № 3 (1997): 891–95. http://dx.doi.org/10.1042/bj3260891.

Full text

Abstract:

Phosphoinositide 3-kinase γ (PI3Kγ) can be activated in vitro by both α and βγ subunits of heterotrimeric G-proteins and does not interact with p85, the regulatory subunit of PI3Kα. Here we demonstrate the binding of Ras to PI3Kγ in vitro. An N-terminal region of PI3Kγ was identified as a binding site for Ras. After co-expression with PI3Kγ in COS-7 cells, Ras induced only a modest increase in PI3K activity compared with the stimulation of PI3Kα by Ras in the same cells.

APA, Harvard, Vancouver, ISO, and other styles

29

Borsari, Chiara, and Matthias P. Wymann. "Targeting Phosphoinositide 3-Kinase – Five Decades of Chemical Space Exploration." CHIMIA 75, no. 12 (2021): 1037. http://dx.doi.org/10.2533/chimia.2021.1037.

Full text

Abstract:

Phosphoinositide 3-kinase (PI3K) takes a key role in a plethora of physiologic processes and controls cell growth, metabolism, immunity, cardiovascular and neurological function, and more. The discovery of wortmannin as the first potent PI3K inhibitor (PI3Ki) in the 1990s provided rapid identification of PI3K-dependent processes, which drove the assembly of the PI3K/protein kinase B (PKB/Akt)/target of rapamycin (mTOR) pathway. Genetic mouse models and first PI3K isoform-specific inhibitors pinpointed putative therapeutic applications. The recognition of PI3K as target for cancer therapy drove

APA, Harvard, Vancouver, ISO, and other styles

30

HEHL, Solveig, Borislav STOYANOV, Wolf OEHRL, Roland SCHÖNHERR, Reinhard WETZKER та Stefan H. HEINEMANN. "Phosphoinositide 3-kinase-γ induces Xenopus oocyte maturation via lipid kinase activity". Biochemical Journal 360, № 3 (2001): 691–98. http://dx.doi.org/10.1042/bj3600691.

Full text

Abstract:

Type-I phosphoinositide 3-kinases (PI3Ks) were characterized as a group of intracellular signalling proteins expressing both protein and lipid kinase activities. Recent studies implicate PI3Ks as mediators of oocyte maturation, but the molecular mechanisms are poorly defined. Here we used the Xenopus oocyte expression system as a model to investigate a possible contribution of the γ-isoform of PI3K (PI3Kγ) in the different pathways leading to cell-cycle progression by monitoring the time course of germinal vesicle breakdown (GVBD). Expression of a constitutive active PI3Kγ (PI3Kγ-CAAX) induced

APA, Harvard, Vancouver, ISO, and other styles

31

Varkaris, Andreas, Ferran Fece de la Cruz, Elizabeth Martin, et al. "Abstract GS03-10: Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations." Cancer Research 84, no. 9_Supplement (2024): GS03–10—GS03–10. http://dx.doi.org/10.1158/1538-7445.sabcs23-gs03-10.

Full text

Abstract:

Abstract Background: PIK3CA mutations occur in ~40% of HR-positive breast cancers, where alpelisib, an orthosteric PI3Kα inhibitor, is FDA-approved in combination with fulvestrant. Although prior studies have identified potential resistance mechanisms, such as PTEN loss, clinical acquired resistance to orthosteric PI3Kα inhibitors and the role of next-generation allosteric PI3Kα inhibitors remain poorly understood. Methods: To identify on-target and off-target alterations potentially mediating resistance to PI3Kα inhibitors, we used a targeted next-generation sequencing assay (Guardant360; Gua

APA, Harvard, Vancouver, ISO, and other styles

32

Bony, Claire, Serge Roche, Ueno Shuichi та ін. "A Specific Role of Phosphatidylinositol 3–Kinase γ". Journal of Cell Biology 152, № 4 (2001): 717–28. http://dx.doi.org/10.1083/jcb.152.4.717.

Full text

Abstract:

Purinergic stimulation of cardiomyocytes turns on a Src family tyrosine kinase–dependent pathway that stimulates PLCγ and generates IP3, a breakdown product of phosphatidylinositol 4,5–bisphosphate (PIP2). This signaling pathway closely regulates cardiac cell autonomic activity (i.e., spontaneous cell Ca2+ spiking). PIP2 is phosphorylated on 3′ by phosphoinositide 3–kinases (PI3Ks) that belong to a broad family of kinase isoforms. The product of PI3K, phosphatidylinositol 3,4,5–trisphosphate, regulates activity of PLCγ. PI3Ks have emerged as crucial regulators of many cell functions including

APA, Harvard, Vancouver, ISO, and other styles

33

Blunt, Matthew D., Matthew J. Carter, Marta Larrayoz, et al. "The Dual PI3K/mTOR Inhibitor PF-04691502 Induces Substantial Apoptosis in Chronic Lymphocytic Leukemia Cells in Vitro and Prolongs Survival in the Eµ-TCL1 Mouse Model." Blood 124, no. 21 (2014): 832. http://dx.doi.org/10.1182/blood.v124.21.832.832.

Full text

Abstract:

Abstract Pharmacological inhibition of specific B cell receptor signalling pathways within chronic lymphocytic leukemia (CLL) cells offers the potential for improved therapeutic options with reduced off target toxicity. Idelalisib, the PI3Kδ selective inhibitor, has been approved for CLL and significantly improved overall survival among patients with relapsed CLL in combination with rituximab compared to rituximab alone. In addition to PI3Kδ however, there are three other Class I PI3K isoforms, PI3Kα, PI3Kβ and PI3Kγ, with PI3Kα known to have a role in CLL survival and chemotaxis. In neutrophi

APA, Harvard, Vancouver, ISO, and other styles

34

Carson, Jeffrey D., Glenn Van Aller, Ruth Lehr та ін. "Effects of oncogenic p110α subunit mutations on the lipid kinase activity of phosphoinositide 3-kinase". Biochemical Journal 409, № 2 (2007): 519–24. http://dx.doi.org/10.1042/bj20070681.

Full text

Abstract:

The PIK3CA gene, encoding the p110α catalytic subunit of Class IA PI3Ks (phosphoinositide 3-kinases), is frequently mutated in many human tumours. The three most common tumour-derived alleles of p110α, H1047R, E542K and E545K, were shown to potently activate PI3K signalling in human epithelial cells. In the present study, we examine the biochemical activity of the recombinantly purified PI3K oncogenic mutants. The kinetic characterizations of the wt (wild-type) and the three ‘hot spot’ PI3K mutants show that the mutants all have approx. 2-fold increase in lipid kinase activities. Interestingly

APA, Harvard, Vancouver, ISO, and other styles

35

Liu, Lixin, Kamal D. Puri, Josef M. Penninger та Paul Kubes. "Leukocyte PI3Kγ and PI3Kδ have temporally distinct roles for leukocyte recruitment in vivo". Blood 110, № 4 (2007): 1191–98. http://dx.doi.org/10.1182/blood-2006-11-060103.

Full text

Abstract:

Abstract Phosphoinositide 3-kinases (PI3Ks) have been considered important in leukocyte motility. PI3Kγ, the class IB PI3K, expressed prominently in leukocytes and also in endothelial cells, mediates leukocyte functional responses induced by chemoattractants. To reveal its role in leukocyte recruitment, we used intravital microscopy to directly visualize leukocyte rolling, adhesion, and emigration in postcapillary venules in PI3Kγ-deficient (PI3Kγ-/-) mice. We report here that PI3Kγ deficiency had no significant effects on leukocyte rolling flux or rolling velocity and minor effects on adhesio

APA, Harvard, Vancouver, ISO, and other styles

36

Cao, Biyin, Jingyu Zhu, Man Wang, et al. "A Novel PI3K Inhibitor Identified By a High Throughput Virtual Screen Displays Potent Activity Against Multiple Myeloma." Blood 124, no. 21 (2014): 4722. http://dx.doi.org/10.1182/blood.v124.21.4722.4722.

Full text

Abstract:

Abstract The phosphatidylinositol-3-kinase (PI3K) has been developed as a promising target for the treatment of many cancers, including hematological malignancies, such as lymphoma, leukemia, and multiple myeloma (MM). Recent clinical trials have demonstrated Idelalisib, a specific PI3Kdelta inhibitor, reached a total 57% of response rate in relapsed indolent lymphoma and 72% of overall complete rate in relapsed chronic lymphocytic leukemia. MM remains fatal as a cancer of plasma cells because of lack of efficient drugs. Therefore, we tried to find novel PI3K inhibitors for MM therapy. To this

APA, Harvard, Vancouver, ISO, and other styles

37

Wyatt, Garhett, Rachel Steinmetz, Traci Lyons, and Weston Porter. "Abstract PO5-05-08: LOSS OF SINGLEMINDED 2S RESULTS IN A PI3K SUBUNIT SWITCH WHICH DRIVES THERAPEUTIC RESISTANCE IN ESTROGEN RECEPTOR POSITIVE BREAST CANCER." Cancer Research 84, no. 9_Supplement (2024): PO5–05–08—PO5–05–08. http://dx.doi.org/10.1158/1538-7445.sabcs23-po5-05-08.

Full text

Abstract:

Abstract Estrogen receptor (ER) + breast cancer (BC) comprises over 70% of BC cases and are targeted via ER modulated therapies. Despite this, ER+BC patients can experience recurrence within 20 years and the majority of BC related deaths can be attributed to metastatic ER+BC. These distant metastases are commonly diagnosed as endocrine therapy resistant. Thus, there is an unmet need to identify novel biomarkers for treating ER+ patients with metastases. We have identified a tumor suppressor gene, singleminded 2s (SIM2s), expressed in breast epithelial cells that inhibits epithelial to mesenchy

APA, Harvard, Vancouver, ISO, and other styles

38

Ascione, Liliana, Paola Zagami, Eleonora Nicolò, Edoardo Crimini, Giuseppe Curigliano, and Carmen Criscitiello. "PIK3CAMutations in Breast Cancer Subtypes Other Than HR-Positive/HER2-Negative." Journal of Personalized Medicine 12, no. 11 (2022): 1793. http://dx.doi.org/10.3390/jpm12111793.

Full text

Abstract:

The phosphoinositide 3-kinase (PI3K) pathway plays a key role in cancer, influencing growth, proliferation, and survival of tumor cells. PIK3CA mutations are generally oncogenic and responsible for uncontrolled cellular growth. PI3K inhibitors (PI3Ki) can inhibit the PI3K/AKT/mTOR pathway, although burdened by not easily manageable toxicity. Among PI3Ki, alpelisib, a selective p110α inhibitor, is approved for the treatment of hormone receptor (HR)+/HER2- PIK3CA mutant metastatic breast cancer (BC) that has progressed to a first line endocrine therapy. PIK3CA mutations are also present in tripl

APA, Harvard, Vancouver, ISO, and other styles

39

Sadasivan, Chandu, Pavel Zhabyeyev, Dina Labib, James A. White, D. Ian Paterson та Gavin Y. Oudit. "Cardiovascular toxicity of PI3Kα inhibitors". Clinical Science 134, № 19 (2020): 2595–622. http://dx.doi.org/10.1042/cs20200302.

Full text

Abstract:

Abstract The phosphoinositide 3-kinases (PI3Ks) are a family of intracellular lipid kinases that phosphorylate the 3′-hydroxyl group of inositol membrane lipids, resulting in the production of phosphatidylinositol 3,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. This results in downstream effects, including cell growth, proliferation, and migration. The heart expresses three PI3K class I enzyme isoforms (α, β, and γ), and these enzymes play a role in cardiac cellular survival, myocardial hypertrophy, myocardial contractility, excitation, and mechanotransduction. The PI3K pathway

APA, Harvard, Vancouver, ISO, and other styles

40

Chawsheen, Mahmoud A., та Hazem A. Al-Bustany. "Docking Study to Predict the Efficacy of Phosphatidylinositol 3-Kinase α Inhibitors". ARO-THE SCIENTIFIC JOURNAL OF KOYA UNIVERSITY 7, № 2 (2019): 47–52. http://dx.doi.org/10.14500/aro.10565.

Full text

Abstract:

The phosphatidylinositol 3-kinase (PI3K) family comprises lipid kinases that cross-link signals between living cells and their surroundings. PI3Ks are classified into several groups and isoforms with specific characteristics and functions. Genes encoding PI3Ks are mutated in several types of cancer, and their isoforms have varying capacity in promoting cell signaling and cancer progression. Many compounds have been introduced as PI3Kα inhibitors, but not all of them have the same inhibitory effects. For successful PI3K-related biomedical experiments, it is vital to select the most specific and

APA, Harvard, Vancouver, ISO, and other styles

41

Maffei, Angelo, Giuseppe Lembo, and Daniela Carnevale. "PI3Kinases in Diabetes Mellitus and Its Related Complications." International Journal of Molecular Sciences 19, no. 12 (2018): 4098. http://dx.doi.org/10.3390/ijms19124098.

Full text

Abstract:

Recent studies have shown that phosphoinositide 3-kinases (PI3Ks) have become the target of many pharmacological treatments, both in clinical trials and in clinical practice. PI3Ks play an important role in glucose regulation, and this suggests their possible involvement in the onset of diabetes mellitus. In this review, we gather our knowledge regarding the effects of PI3K isoforms on glucose regulation in several organs and on the most clinically-relevant complications of diabetes mellitus, such as cardiomyopathy, vasculopathy, nephropathy, and neurological disease. For instance, PI3K α has

APA, Harvard, Vancouver, ISO, and other styles

42

Koyasu, S. "Role of class IA phosphoinositide 3-kinase in B lymphocyte development and functions." Biochemical Society Transactions 32, no. 2 (2004): 320–25. http://dx.doi.org/10.1042/bst0320320.

Full text

Abstract:

PI3K (phosphoinositide 3-kinase) family members control a variety of cellular responses, such as cell growth, survival, cytoskeletal remodelling and the trafficking of intracellular organelles, in many cell types, including lymphocytes. It has been difficult to evaluate the roles of distinct PI3Ks in immune responses, because specific inhibitors for each PI3K are lacking and most stimuli activate multiple PI3Ks. The development of gene-targeted mice has now allowed the elucidation of roles played in vivo by PI3K species in the immune system. Studies on mice deficient in catalytic as well as re

APA, Harvard, Vancouver, ISO, and other styles

43

Okkenhaug, K., A. Bilancio, J. L. Emery, and B. Vanhaesebroeck. "Phosphoinositide 3-kinase in T cell activation and survival." Biochemical Society Transactions 32, no. 2 (2004): 332–35. http://dx.doi.org/10.1042/bst0320332.

Full text

Abstract:

PI3Ks (phosphoinositide 3-kinases) regulate diverse signalling pathways involved in growth, proliferation, survival, differentiation and metabolism. In T cells, PI3Ks can be activated by a number of different receptors, including the TcR (T cell receptor), co-stimulatory receptors, cytokine receptors and chemokine receptors. However, the specific roles of PI3Ks downstream of these receptors vary. An inactivating mutation in the leucocyte-specific PI3K isoform p110 δ results in impaired TcR-dependent proliferation under circumstances where CD28 co-stimulation is blocked or not required. Recruit

APA, Harvard, Vancouver, ISO, and other styles

44

Chen, Yu-Chen Enya, Melinda Lea Burgess, Antje Blumenthal, et al. "Activation of Fc Gamma Receptor-Dependent Responses to Therapeutic Antibodies By Nurse like Cells Requires PI3Kdelta." Blood 132, Supplement 1 (2018): 3128. http://dx.doi.org/10.1182/blood-2018-99-109719.

Full text

Abstract:

Abstract There is a continued reliance on antibody therapies for treating chronic lymphocytic leukaemia (CLL). Whilst the inclusion of antibody therapies in many standard treatment regimes results in good outcomes, acquired resistance remains a significant clinical challenge for many CLL patients resulting in insensitivity to the antibody treatment. Thus, understanding the mechanisms driving treatment resistance is likely to lead to therapies to reverse resistance and improve patient outcomes. Earlier studies from our laboratory have shown that resistance to therapeutic antibodies, in CLL, is

APA, Harvard, Vancouver, ISO, and other styles

45

Consonni, Alessandra, Lina Cipolla, Gianni Guidetti та ін. "Role and regulation of phosphatidylinositol 3-kinase β in platelet integrin α2β1 signaling". Blood 119, № 3 (2012): 847–56. http://dx.doi.org/10.1182/blood-2011-07-364992.

Full text

Abstract:

Abstract Integrin α2β1–mediated adhesion of human platelets to monomeric type I collagen or to the GFOGER peptide caused a time-dependent activation of PI3K and Akt phosphorylation. This process was abrogated by pharmacologic inhibition of PI3Kβ, but not of PI3Kγ or PI3Kα. Moreover, Akt phosphorylation was undetectable in murine platelets expressing a kinase-dead mutant of PI3Kβ (PI3KβKD), but occurred normally in PI3KγKD platelets. Integrin α2β1 failed to stimulate PI3Kβ in platelets from phospholipase Cγ2 (PLCγ2)–knockout mice, and we found that intracellular Ca2+ linked PLCγ2 to PI3Kβ activ

APA, Harvard, Vancouver, ISO, and other styles

46

Laurent, Pierre-Alexandre, Cédric Garcia, Marie-Pierre Gratacap та ін. "The class I phosphoinositide 3-kinases α and β control antiphospholipid antibodies-induced platelet activation". Thrombosis and Haemostasis 115, № 06 (2016): 1138–46. http://dx.doi.org/10.1160/th15-08-0661.

Full text

Abstract:

SummaryAntiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL) associated with increased thrombotic risk and pregnancy morbidity. Although aPL are heterogeneous auto-antibodies, the major pathogenic target is the plasma protein β2-glycoprotein 1. The molecular mechanisms of platelet activation by aPL remain poorly understood. Here, we explored the role of the class IA phosphoinositide 3-kinase (PI3K) α and β isoforms in platelet activation by aPL. Compared to control IgG from healthy individuals, the IgG fraction isolated from

APA, Harvard, Vancouver, ISO, and other styles

47

Park, Jei Hyoung, Kyoung Jin Nho, Ji Young Lee та ін. "Anti-Ischemic Effects of PIK3IP1 Are Mediated through Its Interactions with the ETA-PI3Kγ-AKT Axis". Cells 11, № 14 (2022): 2162. http://dx.doi.org/10.3390/cells11142162.

Full text

Abstract:

Oxidative stress, caused by the accumulation of reactive oxygen species (ROS) during acute myocardial infarction (AMI), is one of the main factors leading to myocardial cell damage and programmed cell death. Phosphatidylinositol-3-kinase-AKT (PI3K-AKT) signaling is essential for regulating cell proliferation, differentiation, and apoptosis. Phosphoinositide-3-kinase (PI3K)-interacting protein 1 (PIK3IP1) is an intrinsic inhibitor of PI3K in various tissues, but its functional role during AMI remains unknown. In this study, the anti-ischemic role of PIK3IP1 in an in vitro AMI setting was evalua

APA, Harvard, Vancouver, ISO, and other styles

48

Brosinsky, Paulin, Julia Bornbaum, Björn Warga та ін. "PI3K as Mediator of Apoptosis and Contractile Dysfunction in TGFβ1-Stimulated Cardiomyocytes". Biology 10, № 7 (2021): 670. http://dx.doi.org/10.3390/biology10070670.

Full text

Abstract:

Background: TGFβ1 is a growth factor that plays a major role in the remodeling process of the heart by inducing cardiomyocyte dysfunction and apoptosis, as well as fibrosis thereby restricting heart function. TGFβ1 mediates its effect via the TGFβ receptor I (ALK5) and the activation of SMAD transcription factors, but TGFβ1 is also known as activator of phosphoinositide-3-kinase (PI3K) via the non-SMAD signaling pathway. The aim of this study was to investigate whether PI3K is also involved in TGFβ1–induced cardiomyocytes apoptosis and contractile dysfunction. Methods and Results: Incubation o

APA, Harvard, Vancouver, ISO, and other styles

49

Kaur, Harjeet, Chang Shin Park, Jodee M. Lewis, and Jason M. Haugh. "Quantitative model of Ras–phosphoinositide 3-kinase signalling cross-talk based on co-operative molecular assembly." Biochemical Journal 393, no. 1 (2005): 235–43. http://dx.doi.org/10.1042/bj20051022.

Full text

Abstract:

In growth-factor-stimulated signal transduction, cell-surface receptors recruit PI3Ks (phosphoinositide 3-kinases) and Ras-specific GEFs (guanine nucleotide-exchange factors) to the plasma membrane, where they produce 3′-phosphorylated phosphoinositide lipids and Ras-GTP respectively. As a direct example of pathway networking, Ras-GTP also recruits and activates PI3Ks. To refine the mechanism of Ras–PI3K cross-talk and analyse its quantitative implications, we offer a theoretical model describing the assembly of complexes involving receptors, PI3K and Ras-GTP. While the model poses the possibi

APA, Harvard, Vancouver, ISO, and other styles

50

Uche, Uzodinma, and Lawrence Kane. "PIK3IP1- A novel negative regulator of PI3K (IRM10P.743)." Journal of Immunology 192, no. 1_Supplement (2014): 129.10. http://dx.doi.org/10.4049/jimmunol.192.supp.129.10.

Full text

Abstract:

Abstract Phosphatidylinositide-3-Kinases (PI3Ks) are a family of lipid kinases that play important intracellular signaling roles in cellular functions such as cell proliferation, motility, growth, intracellular trafficking, differentiation and survival. PI3K produces PIP3 which further facilitates the activation of downstream effectors such as Akt and PDK1. These effectors facilitate the cellular processes associated with PI3K activity. Conversely, because of the nature of PI3Ks roles, dysregulation of PI3K is implicated in many cancers. PTEN, SHIP and INPP4B are negative regulators of PI3K ac

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!