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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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.
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PI3Kγ inhibitor 7
0 ImagesCat. No.: HY-153703CAS No.: 2575863-25-9PI3Kγ inhibitor 7 (compound 2) is a potent and orally active PI3Kγ inhibitor with IC50 values of 4768, 878.1, 3.42, 355.2 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively. PI3Kγ inhibitor 7 shows antitumor activity. PI3Kγ inhibitor 7 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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MEK/PI3K-IN-1
0 ImagesCat. No.: HY-144692CAS No.: 2281803-28-7
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IHMT-PI3K-455
0 ImagesCat. No.: HY-149493CAS No.: 3047746-40-4IHMT-PI3K-455 (Compound 15u) is a potent, selective, orally active PI3Kγ/δ dual inhibitor with IC50s of 7.1 nM and 0.57 nM for PI3Kγ and PI3Kδ, respectively. IHMT-PI3K-455 suppresses the AKT phosphorylation. IHMT-PI3K-455 inhibits tumor growth by recruiting and activating more CD8+ killing T cells.IHMT-PI3K-455 is used in cancer research.
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PI3Kδ-IN-12
0 ImagesCat. No.: HY-149235PI3Kδ-IN-12 (compound 13) is a PI3Kδ inhibitor (pIC50 = 5.8), with pKi values of 8.0/6.5/6.4/6.7 for PI3Kδ/γ/β/α, respectively. PI3Kδ-IN-12 can be used in the study of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
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PROTAC PI3Kδ degrader-1
0 ImagesCat. No.: HY-176239PROTAC PI3Kδ degrader-1 is a Lysine-targeted covalent PI3Kδ PROTAC degrader with a DC50 of 3.98 nM. PROTAC PI3Kδ degrader-1 has a potent antiproliferative activity and selective PI3Kδ inhibition (IC50: 8 nM). PROTAC PI3Kδ degrader-1 also significantly degrades p-AKT, induces cell cycle arrest in G1 phase and prompts cell apoptosis and autophagy. PROTAC PI3Kδ degrader-1 effectively inhibits the tumor growth in SU-DHL-6 xenograft mice model.
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PP162
0 ImagesCat. No.: HY-134469CAS No.: 1092788-97-0PP162 is a selective DNA-dependent protein kinase (DNA-PK) inhibitor with an IC50 of 53 nM. PP162 selectively inhibits DNA-PK by binding to a conserved hydrophobic pocket. PP162 exhibits weak inhibitory activity against various tyrosine kinases and PI3K family members. PP162 can be used for research on selective kinase targeting.
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ST-168
0 ImagesCat. No.: HY-120281CAS No.: 2126038-25-1ST-168 is an orally active MEK/PI3K inhibitor with an IC50 of 182 nM against MEK1 and IC50 values of 69.2, 41.7, 1482 and 2293 nM against PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ respectively. ST-168 completely inhibits the phosphorylation of ERK1/2 and AKT and induces cancer cell death in a 3D tumor sphere model. ST-168 demonstrates significant antitumor effects in the A375 melanoma mouse model. ST-168 improves the ocular toxicity profile of MEK inhibitors, showing lower caspase activation levels, indicating reduced apoptosis induction. ST-168 can be used in melanoma research.
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PI3Kδ-IN-24
0 ImagesCat. No.: HY-175002CAS No.: 3051829-20-7PI3Kδ-IN-24 is a selective PI3Kδ inhibitor (IC50 = 0.1 nM). PI3Kδ-IN-24 exhibits significant antiproliferative effects against PI3Kδ-overexpressing cancer cell lines. PI3Kδ-IN-24 reduces p-AKT levels and induces cell cycle arrest and apoptosis in tumor cells. PI3Kδ-IN-24 is useful in cancer research, such as diffuse large B-cell lymphoma (DLBCL).
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PI3K-IN-60
0 ImagesCat. No.: HY-17651CAS No.: 2504036-13-7PI3K-IN-60 (Compound 34) is a highly selective phosphatidylinositol 3-kinase gamma (PI3Kγ) inhibitor. PI3K-IN-60 is promising for research of autoimmune diseases (e.g., multiple sclerosis) and cancers (e.g., breast cancer, pancreatic ductal adenocarcinoma).
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PI3Kα-IN-14
0 ImagesCat. No.: HY-157125CAS No.: 3026856-46-9PI3Kα-IN-14 (compound F8) is a selective PI3Kα inhibitor with an IC50 of 0.14 nM. PI3Kα-IN-14 induces a great decrease in mitochondrial membrane which caused cell cycle arrest at G1 phase and apoptosis in U87-MG cells. PI3Kα-IN-14 shows significant anti-proliferative activities against three tumor-derived cell lines (PC-3: IC50 of 0.28 μM; HCT-116: IC50 of 0.57 μM; and U87-MG: IC50 of 1.37 μM).
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PI3Kδ/γ-IN-2
0 ImagesCat. No.: HY-146789CAS No.: 2412195-89-0
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DHW-208
0 ImagesCat. No.: HY-128633CAS No.: 2269470-35-9PI3K-IN-4 is a potent Pan-PI3K inhibitor. PI3K-IN-4 has high activity for three PI3K isoforms with the IC50 values of picomole. PI3K-IN-4 shows superior inhibitory activity against PI3Kα (IC50 = 0.20 nM), PI3Kβ (IC50 = 2.99 nM), PI3Kδ (IC50 = 0.48 nM) and PI3Kγ (IC50 = 0.58 nM) and has no significant activity against EGFR. PI3K-IN-4 inhibits cancer cell growth though PI3K/Akt signaling pathway, leading to the inhibition of colony formation and the induction of apoptosis. PI3K-IN-4 can be used for lung, colon and breast cancer research.
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PI3K/HDAC-IN-4
0 ImagesCat. No.: HY-172889CAS No.: 3085191-45-0PI3K/HDAC-IN-4 (Compound 31f) is a PI3K/HDAC dual inhibitor (IC50: 0.2μM). PI3K/HDAC-IN-4 shows high selectivity for HDAC1-3 (IC50 values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively). PI3K/HDAC-IN-4 is a potent PIK3 inhibitor with IC50 values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. PI3K/HDAC-IN-4 significantly induces tumor cell apoptosis by simultaneously inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. PI3K/HDAC-IN-4 exhibits potent antiproliferative activity in a variety of tumor cell lines (e.g., MV4-11, Jeko-1, HL60, and MCF-7, with IC50 values of 0.2, 0.9, 0.8, and 1.5 μM, respectively). PI3K/HDAC-IN-4 can be used in the study of lymphoma and leukemia.
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SJY26
0 ImagesCat. No.: HY-178485SJY26 is a PI3K/HDAC dual-target inhibitor with IC50s of 0.59 nM (PI3Kα and PI3Kδ), 2.02 nM (PI3Kγ), 12.69 nM (PI3Kβ) and 114 nM (HDAC1). SJY26 exhibits potent broad-spectrum anti-proliferative activity, and is particularly sensitive to Jurkat and PC9R cells. SJY26 inhibited the migration of PC9R cells, arrested the cell cycle and induced cell apoptosis. SJY26 reduces AKT phosphorylation, and decreases histone H3 deacetylation (Ac-H3). SJY26 can be used for the studies of non-small cell lung cancer and leukemia.
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PI3Kα-IN-8
0 ImagesCat. No.: HY-147983CAS No.: 2315320-24-0PI3Kα-IN-8 (Compound 9g) is a selective PI3Kα inhibitor with an IC50 of 0.012 μM. PI3Kα-IN-8 increases intracellular reactive oxygen species level, decreases mitochondrial membrane potential and induces apoptosis.
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PI3Kδ-IN-26
0 ImagesCat. No.: HY-175734CAS No.: 2019131-11-2PI3Kδ-IN-26 (Compound 58) is a selective and orally active PI3Kδ inhibitor with an IC50 of 14 nM. PI3Kδ-IN-26 significantly attenuates the inflammatory responses in house dust mite (HDM) induced chronic asthma mouse models. PI3Kδ-IN-26 can be used for inflammatory, autoimmune and hyperproliferative diseases research.
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CC-M-1
0 ImagesCat. No.: HY-179464CAS No.: 3079943-00-0CC-M-1 is a potent and selective PI3K/mTOR inhibitor. CC-M-1 inhibits PI3Kα/β/γ/δ and mTOR with IC50 values of 0.68, 1.02, 1.03, 8.03, and 15 nM, respectively. CC-M-1 inhibits the proliferation of colorectal cancer cell lines, including HCT-116 (IC50 = 0.38 μM) and HT-29 (IC50 = 1.70 μM). CC-M-1 can be used for colorectal cancer (CRC) research.
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RV-6153
0 ImagesCat. No.: HY-124459CAS No.: 1628139-03-6RV-6153 is a potent and selective dual inhibitor of PI3Kδ and PI3Kγ, with IC50 values of 2.5 nM and 28 nM, respectively. RV-6153 dually inhibits PI3Kδ and PI3Kγ, blocking Akt phosphorylation, thereby inhibiting ROS production and cytokine release at the cellular level, and reducing neutrophil and macrophage accumulation in the airways in vivo. RV-6153 can be used in research on chronic obstructive pulmonary disease, asthma, and other inflammatory diseases.
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PI3Kγ inhibitor 1
0 ImagesCat. No.: HY-10549CAS No.: 1172118-03-4PI3Kγ inhibitor 1 is a PI3Kδ and PI3Kγ inhibitor extracted from patent WO2014004470A1, Compound 168 in Table 4, has IC50s of <100 nM.
