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 (182)
Related Products (182)
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LNP23
0 ImagesCat. No.: HY-189462CAS No.: 3136664-01-9LNP23 is a selective PI3Kα inhibitor with an IC50 of 5.15 nM. LNP23 inhibits PI3K/AKT signaling and induces apoptosis and G1 phase arrest in MCF-7 cells. LNP23 also inhibits cancer cell proliferation, colony formation, and migration. LNP23 can be used for breast cancer and lung adenocarcinoma research.
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NVP-CLR457
0 ImagesCat. No.: HY-146260CAS No.: 1453082-52-4NVP-CLR457 (compound 40) is an orally active, potent and balanced pan-class I PI3K inhibitor. NVP-CLR457 shows a clear dose-dependent PK/PD/efficacy relationship. NVP-CLR457 has antitumor activity.
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PI3K/HDAC-IN-2
0 ImagesCat. No.: HY-146159CAS No.: 2361418-65-5PI3K/HDAC-IN-2 is a potent dual PI3K/HDAC inhibitor with IC50s of 226 nM, 279 nM, 467 nM, 29 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively, and IC50s of 1.3 nM, 3.4 nM, 972 nM, 17 nM, 12 nM for HDAC1, HDAC2, HDC4, HDAC6, HDAC8, respectively. PI3K/HDAC-IN-2 exhibits PI3Kδ and class I and IIb HDAC selectivity. PI3K/HDAC-IN-2 has remarkable anticancer effects.
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Pabgraminone C
0 ImagesCat. No.: HY-184119CAS No.: 3061276-55-6Synonyms: IM502Pabgraminone C (IM502) is a Fungal metabolite and PI3Kγ inhibitor with an IC50 of 61.7 nM against PI3Kγ. Pabgraminone C shifts the STAT signaling pathway in cells from an immunosuppressive STAT3/STAT6-dominant profile to an immunostimulatory STAT1/STAT2-dominant profile, driving cells toward a pro-inflammatory phenotype. Pabgraminone C reprograms cells from an immunosuppressive state to an immunostimulatory state, reversing their suppressive effect on anti-tumor immunity. Pabgraminone C inhibits established tumor growth and metastasis across multiple cancer types. Pabgraminone C overcomes resistance to PD-1 checkpoint blockade strategies. Pabgraminone C can be used in research related to liver cancer, melanoma, and colorectal cancer.
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PI3Kα-IN-29
0 ImagesCat. No.: HY-179623PI3Kα-IN-29 is a potent, orally active and selective PI3Kα with an IC50 of 2.5 nM. PI3Kα-IN-29 exhibits >400-fold selectivity over PI3Kβ/δ/γ/mTOR. PI3Kα-IN-29 selectively degrades the H1047R mutant p110α protein and inhibits PI3Kα kinase activity. PI3Kα-IN-29 suppresses PI3K/AKT/mTOR signaling, induces G1 arrest, and inhibits migration. PI3Kα-IN-29 inhibits tumor growth in a T47 mouse model. PI3Kα-IN-29 can be used for the research of breast cancer.
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SU-11752
0 ImagesCat. No.: HY-114923CAS No.: 688036-19-3SU-11752 is an inhibitor for DNA-dependent protein kinase (DNA-PK) with an IC50 of 0.13 μM. SU-11752 inhibits PI3K p110γ kinase with IC50 of 1.1 μM. SU-11752 binds competitively for ATP-site in DNA-PK, results in inhibition of intracellular DNA double-strand break repair and increases the sensitivity of cells to radiotherapy.
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AZD-7648 (GMP)
0 ImagesCat. No.: HY-111783GCAS No.: 2230820-11-6AZD-7648 (GMP) is AZD-7648 (HY-111783) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. AZD-7648 is a potent, orally active, selective DNA-PK inhibitor with an IC50 of 0.6 nM. AZD-7648 induces apoptosis and shows antitumor activity.
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PF-376304
0 ImagesCat. No.: HY-107387CAS No.: 851757-93-2PF-376304 is an orally active non-specific class I phosphoinositide 3-kinase (PI3K) inhibitor with an IC50 of 0.197 μM against PI3Kγ. PF-376304 induces dose-dependent glucose and lipid metabolic disorders in rats, causes rapid death at high doses, and leads to metabolic abnormalities that are self-reversible at low doses. PF-376304 is applicable to the research of metabolic and inflammatory diseases.
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FOXM1-IN-3
0 ImagesCat. No.: HY-181076Purity: 99.59%FOXM1-IN-3 is a potent FOXM1 inhibitor. FOXM1-IN-3 downregulates FOXM1 expression at protein and mRNA levels, suppressing downstream effectors CCNB1 and CDC25. FOXM1-IN-3 induces G2/M cell cycle arrest and apoptosis in colorectal cancer cells. FOXM1-IN-3 inhibits colony formation and cell migration in colorectal cancer cells. FOXM1-IN-3 targets the cancer stem cell phenotype in colorectal cancer cells, reducing cancer stem cell marker expression. FOXM1-IN-3 reduces tumor growth in a zebrafish xenograft model. FOXM1-IN-3 can be used for the research of colorectal cancer.
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PI3K/mTOR-IN-20
0 ImagesCat. No.: HY-180556PI3K/mTOR-IN-20 is a selective dual PI3K/mTOR inhibitor. PI3K/mTOR-IN-20 demonstrates nanomolar antiproliferative effects with IC50s of 0.380 and 0.090 μM for MRC-5 and Mlg2908 cells. PI3K/mTOR-IN-20 reduces Ashcroft scores, hydroxyproline content, collagen deposition, and downregulates fibrosis-related proteins, while restoring lung architecture in a Bleomycin-induced pulmonary fibrosis model. PI3K/mTOR-IN-20 shows a favorable safety profile with steady weight recovery and no distinct liver or kidney toxicity. PI3K/mTOR-IN-20 can be used for fetal lung fibroblasts research.
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AS-605240 potassium
0 ImagesCat. No.: HY-10109AAS-605240 (potassium) is an orally active PI3Kγ inhibitor (IC50: 8 nM; Ki: 7.8 nM). AS-605240 (potassium) inhibits MCP-1- and CSF1-induced PKB phosphorylation (IC50 values are 0.181 and 0.550 µM, respectively). AS-605240 (potassium) reduces neutrophil recruitment in RANTES (CCL5)- and thioglycolate-induced peritonitis mouse models (EC50 values are 9.1 and 10 mg/kg, respectively). AS-605240 (potassium) ameliorates αCII-IA-induced arthritis in mice.
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MEK/PI3K-IN-2
0 ImagesCat. No.: HY-144693CAS No.: 2281803-33-4
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PP487
0 ImagesCat. No.: HY-15268CAS No.: 1092787-12-6
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LCI40
0 ImagesCat. No.: HY-183770LCI40 is an orally active dual PI3K/BRD4 inhibitor (PI3Kα IC50 = 0.071 μM, PI3Kβ IC50 = 0.17 μM, PI3Kγ IC50 = 0.66 μM, PI3Kδ IC50 = 0.072 μM, BRD4 BD1 IC50 = 0.19 μM, and BRD4 BD2 IC50 = 1.88 μM. LCI40 inhibits phosphorylation of pAKT (S473) and suppresses c-MYC levels in mantle cell lymphoma cells. LCI40 displays immunomodulatory capacity with minimal toxicity to normal mouse immune cells. LCI40 can be used for the research of mantle cell lymphoma.
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HM5023507
0 ImagesCat. No.: HY-177277CAS No.: 1549766-06-4HM5023507 is an orally active and selective PI3Kδ/γ inhibitor with IC50s of 4 and 5 μM for PI3Kδ and PI3Kγ over PI3Kβ and PI3Kα. HM5023507 attenuates the PI3Kδ/γ signaling in human basophils. HM5023507 also attenuates the activation and function of human B and T cells and cytokine and IgG production during cocultures, and Th17 differentiation of CD4 T cells. HM5023507 inhibited semiestablished collagen-induced arthritic inflammation in the rat models. HM5023507 can be used for inflammatory diseases like rheumatoid arthritis research.
