PI3Kγ
PI3Kγ is a Class I PI3K isoform that generates PIP3 and supports leukocyte signaling during inflammation[1]. Mechanistically, PI3Kγ acts downstream of GPCRs, where p110γ couples with regulatory subunits to control chemoattractant-driven signaling[2]. In inflammatory models, PI3Kγ-null neutrophils show impaired PIP3 production, Akt activation, respiratory burst, and motility, while macrophages show reduced chemotactic migration and defective accumulation in septic peritonitis[3]. In cancer models, macrophage PI3Kγ controls a switch between immune stimulation and immune suppression through Akt/mTOR, NFκB, and C/EBPβ signaling[4]. Compared with related isoforms, PI3Kγ is the only Class IB PI3K catalytic isoform, whereas PI3Kα, PI3Kβ, and PI3Kδ belong to Class IA[5]. This distinction supports isoform-focused experimental design, especially when separating myeloid-cell PI3Kγ biology from lymphocyte-enriched PI3Kδ signaling[5][6]. For research applications, selective PI3Kγ inhibition reshaped suppressive myeloid cells and improved checkpoint blockade responses in mouse tumor models[7]. Dual PI3Kδ/PI3Kγ inhibitors such as IPI-145 provide tools for testing combined innate and adaptive immune PI3K signaling in biochemical, cellular, and in vivo assays[8].
References:
- [1]. Hawkins PT, et al. PI3K signalling in inflammation. Biochim Biophys Acta. 2015 Jun;1851(6):882-97. [Content Brief]
- [2]. Vadas O, et al. Molecular determinants of PI3Kγ-mediated activation downstream of G-protein-coupled receptors (GPCRs). Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18862-7. [Content Brief]
- [3]. Hirsch E, et al. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science. 2000 Feb 11;287(5455):1049-53. [Content Brief]
- [4]. Kaneda MM, et al. PI3Kγ is a molecular switch that controls immune suppression. Nature. 2016 Nov 17;539(7629):437-442. [Content Brief]
- [5]. Lanahan SM, et al. The role of PI3Kγ in the immune system: new insights and translational implications. Nat Rev Immunol. 2022 Nov;22(11):687-700. [Content Brief]
- [6]. Okkenhaug K. Signaling by the phosphoinositide 3-kinase family in immune cells. Annu Rev Immunol. 2013;31:675-704. doi: 10.1146/annurev-immunol-032712-095946. Epub 2013 Jan 16. PMID: 23330955; PMCID: PMC4516760. et al. Signaling by the phosphoinositide 3-kinase family in immune cells. Annu Rev Immunol. 2013;31:675-704. [Content Brief]
- [7]. De Henau O, et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature. 2016 Nov 17;539(7629):443-447. [Content Brief]
- [8]. Wojnowska M, et al. Autophosphorylation activity of a soluble hexameric histidine kinase correlates with the shift in protein conformational equilibrium. Chem Biol. 2013 Nov 21;20(11):1411-20. [Content Brief]
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PI3Kγ Related Products (185)
Related Products (185)
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FD223
0 ImagesFD223 is a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor. FD223 displays high potency (IC50=1 nM) and good selectivity over other isoforms (IC50s of 51 nM, 29 nM and 37 nM, respectively for α, β and γ). FD223 exhibits efficient inhibition of the proliferation of acute myeloid leukemia (AML) cell lines by suppressing p-AKT Ser473 thus causing G1 phase arrest during the cell cycle. FD223 has potential for the research of leukemia such as AML.
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CHMFL-PI3KD-317
0 ImagesCHMFL-PI3KD-317 is a highly potent, selective and orally active PI3Kδ inhibitor, with an IC50 of 6 nM, and exhibits over 10-1500 fold selectivity over other class I, II and III PIKK family isoforms, such as PI3Kα (IC50, 62.6 nM), PI3Kβ (IC50, 284 nM), PI3Kγ (IC50, 202.7 nM), PIK3C2A (IC50, >10000 nM), PIK3C2B (IC50, 882.3 nM), VPS34 (IC50, 1801.7 nM), PI4KIIIA (IC50, 574.1 nM) and PI4KIIIB (IC50, 300.2 nM). CHMFL-PI3KD-317 inhibits PI3Kδ-mediated Akt T308 phosphorylation in Raji cells, with an EC50 of 4.3 nM. CHMFL-PI3KD-317 has antiproliferative effects on cancer cells.
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OMS14
0 ImagesOMS14 is exhibits inhibitory activity for phosphoinositide 3-kinase γ (PI3Kγ) and PIK3CD/PIK3R1, which inhibits 19% PI3Kγ and 65% PIK3CD/PIK3R1 activity at 100 μM. OMS14 exhibits anticancer efficacy in various cancer cells.
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PARP/PI3K-IN-1
0 ImagesPARP/PI3K-IN-1 (compound 15) is a potent PARP/PI3K inhibitor with pIC50 values of 8.22, 8.44, 8.25, 6.54, 8.13, 6.08 for PARP-1, PARP-2, PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ, respectively. PARP/PI3K-IN-1 is a highly effective anticancer compound targeted against a wide range of oncologic diseases.
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PKI-179 hydrochloride
0 ImagesPKI-179 hydrochloride is a potent and orally active dual PI3K/mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 hydrochloride also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 hydrochloride shows anti-tumor activity in vivo.
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FD274
0 ImagesFD274 is a highly potent PI3K/mTOR dual inhibitor with IC50s of 0.65 nM, 1.57 nM, 0.65 nM, 0.42 nM, and 2.03 nM against PI3Kα/β/γ/δ and mTOR, respectively. FD274 exhibits significant anti-proliferation of AML cell lines (HL-60 and MOLM-16). FD274 arrests HL-60 cell cycle at G1 phase and increases apoptosis. FD274 demonstrates dose-dependent inhibition of tumor growth in the HL-60 xenograft model. FD274 has the potential for acute myeloid leukemia research.
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MJ04
0 ImagesMJ04 is a selective inhibitor for Janus Kinase 3 (JAK 3) with an IC50 of 2.03 nM. MJ04 inhibits T cell differentation and inhibits the proinfammatory cytokines in Lipopolysaccharides (HY-D1056)‑induced macrophages. MJ04 exhibits good pharmacokinetic characters in mice, promotes hair growth in DHT-induced androgenetic alopecia (AGA) in athymic mice model, without significant toxicity (LD50 >2 g/kg).
