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]
-
PI3Kγ Related Products (185)
Related Products (185)
-
CHMFL-PI4K-127
0 ImagesCHMFL-PI4K-127 (compound 15g) is an orally active, potent and high selective PfPI4K (Plasmodium falciparum PI4K kinase) inhibitor, with an IC50 of 0.9 nM. CHMFL-PI4K-127 exhibits potent activity against 3D7 Plasmodium falciparum, with an EC50 of 25.1 nM. CHMFL-PI4K-127 shows antimalaria efficacy.
-
PI3Kδ-IN-16
0 ImagesPI3Kδ-IN-16 is a potent and selective PI3Kδ inhibitor with an IC50 value of 0.9 nM. PI3Kδ-IN-16 has a strong anti-proliferative effect on SU-DHL-6 cells, causing cell cycle arrest and inducing apoptosis. PI3Kδ-IN-16 tightly bins to PI3Kδ protein with a planar-shaped conformation. The kinase activity of PI3Kδ-IN-16 which is ~378-fold over PI3Kα, 412-fold over PI3Kβ, and 10-fold over PI3Kγ. PI3Kδ-IN-16 can be used for the study of hematologic malignancies.
-
Umbralisib tosylate
0 ImagesCat. No.: HY-12279ACAS No.: 1532533-72-4Synonyms: TGR-1202 tosylate; RP5264 tosylateUmbralisib (TGR-1202) tosylate is an orally active, potent and selective dual PI3Kδ and casein kinase-1-ε (CK1ε) inhibitor, with EC50 of 22.2 nM and 6.0 μM, respectively. Umbralisib tosylate exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib tosylate can be used for haematological malignancies reseach.
-
Umbralisib sulfate
0 ImagesCat. No.: HY-12279BCAS No.: 1532533-75-7Synonyms: TGR-1202 sulfate; RP-5264 sulfateUmbralisib (TGR-1202) sulfate is an orally active, potent and selective dual PI3Kδ and casein kinase-1-ε (CK1ε) inhibitor, with EC50 of 22.2 nM and 6.0 μM, respectively. Umbralisib sulfate exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib sulfate can be used for haematological malignancies reseach.
-
PI3K/HDAC-IN-1
0 ImagesCat. No.: HY-128582CAS No.: 2361418-52-0
-
PI3Kγ inhibitor 2
0 ImagesCat. No.: HY-112286CAS No.: 1315538-79-4PI3Kγ inhibitor 2 (Compound 16) is an orally bioavailable, CNS-penetrant, isoform selective PI3Kγ inhibitor with a Ki of 4 nM.
-
JMC14
0 ImagesCat. No.: HY-174366CAS No.: 2256080-83-6JMC14 is a selective and orally active PI3Kδ and CSF1R inhibitor with IC50 values of 12 nM and 143 nM, respectively. JMC14 preferentially inhibits PI3Kδ-mediated signaling at the cellular level. JMC14 demonstrates potent antitumor activity against B-cell lymphomas and triple-negative breast cancer (TNBC) in both in vitro and vivo studies. JMC14 can be used for the study of antitumor immunity.
-
PI3Kγ inhibitor 4
0 ImagesCat. No.: HY-132299CAS No.: 1821038-80-5PI3Kγ inhibitor 4 is a potent, selective and orally active inhibitor of PI3Kγ, with an IC50 of 40 nM. PI3Kγ inhibitor 4 shows ∼7, 43, and 18-fold selectivity for PI3Kγ over the α, β, and δ isoforms, respectively. PI3Kγ inhibitor 4 can be used for the research of airway inflammation.
-
AM-8508
0 ImagesCat. No.: HY-120116CAS No.: 1338483-67-2AM-8508 is an orally bioactive PI3Kδ inhibitor with an IC50 of 0.016 μM. AM-8508 selectively inhibits PI3Kδ, thereby blocking AKT phosphorylation mediated by the B cell receptor. AM-8508 suppresses the formation of antigen-specific IgG and IgM in rats immunized with keyhole limpet hemocyanin. AM-8508 can be used for the research of inflammatory diseases.
-
AM-1430
0 ImagesCat. No.: HY-115814CAS No.: 1975263-74-1AM-1430 is an efficient, highly selective and orally active small molecule inhibitor of PI3Kδ with an IC50 of 4.6 nM. AM-1430 exhibits IC50s for PI3Kα, PI3Kβ and PI3Kγ of 14.18, 2.2 and 3.22 μM, respectively. AM-1430 inhibits B cell proliferation and exhibits excellent in vivo activity in pAKT inhibition models and the hemoglobin (KLH) immune response model. AM-1430 can be used for the study of inflammation and autoimmune diseases.
-
T133
0 ImagesCat. No.: HY-181650CAS No.: 3101627-06-6T133 is an orally active ATP-competitive mTOR inhibitor with an IC50 of 0.34 nM and a Ki of 0.17 nM. T133 suppresses phosphorylation of AKT, S6K1, and 4EBP1. T133 inhibits cancer cell proliferation and migration, induces apoptosis, cell cycle arrest, and autophagy. T133 exhibits dose-dependent antitumor efficacy in xenograft mouse models. T133 can be used for the research of cancer, such as gastric cancer and lung cancer.
-
PROTAC PI3Kα/δ degrader-1
0 ImagesCat. No.: HY-182083PROTAC PI3Kα/δ degrader-1 is an orally active PI3Kα/δ PROTAC degrader, with an IC50 of 0.34 nM for PI3Kα and 1.85 nM for PI3Kδ. PROTAC PI3Kα/δ degrader-1 inhibits the proliferation and migration of cancer cells, induces G1-phase cell cycle arrest and PI3Kα degradation. PROTAC PI3Kα/δ degrader-1 suppresses tumor growth in breast cancer xenograft mouse models. PROTAC PI3Kα/δ degrader-1 can be used for the research of breast cancer.
-
DHW-221
0 ImagesCat. No.: HY-130133CAS No.: 2378831-21-9DHW-221 is a potent orally active dual PI3K/mTOR inhibitor, exhibiting low nanomolar potency against all four Class I PI3K isoforms and mTOR (PI3Kα, IC50 = 0.50 nM; PI3Kβ, IC50 = 1.9 nM; PI3Kγ, IC50 = 1.8 nM; PI3Kδ, IC50 = 0.74 nM; mTOR, IC50 = 3.9 nM). DHW-221 exerts antitumor effects by blocking the PI3K/Akt/mTOR pathway and inducing mitochondrial apoptosis and paraptosis (via Endoplasmic Reticulum (ER) stress and MAPK signaling) and arrests cell cycle, thereby inhibiting cell migration, invasion and angiogenesis. DHW-221 inhibits tumor growth in both the A549/Taxol (HY-B0015) and the HCC827 xenograft mouse models. DHW-221 can be used for non-small cell lung cancer (NSCLC), colon and breast cancer research.
