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.

[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.

[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.

[4]. Kaneda MM, et al. PI3Kγ is a molecular switch that controls immune suppression. Nature. 2016 Nov 17;539(7629):437-442.

[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.

[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.

[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.

PI3Kγ Related Products (179):

By Type:	Pan (137) Selective (29)
By Effects:	Inhibitors (171) Degraders (4) Substrate (1)

Cat. No.	Product Name	Effect	Purity

HY-19312

3-Methyladenine	Inhibitor	99.91%
3-Methyladenine (3-MA) is a PI3K inhibitor. 3-Methyladenine is a widely used inhibitor of autophagy via its inhibitory effect on class III PI3K.

HY-18085

Quercetin	Inhibitor	99.80%
Quercetin, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC₅₀ of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively.

HY-15244

Alpelisib	Inhibitor	99.95%
Alpelisib (BYL-719) is an orally active PI3Kα-selective inhibitor that blocks the conversion of PIP2 to PIP3, thereby inhibiting pathways including PI3K/AKT/mTOR, MAPK/ERK, Notch and JAK-STAT. Alpelisib also induces apoptosis, G0/G1 phase arrest and senescence; it significantly inhibits the proliferation, self-renewal, stemness and epithelial-mesenchymal transition (EMT) of tumor cells, reduces cancer stem cell populations and decreases the expression of stem cell markers. Alpelisib not only enhances the sensitivity to Eribulin (HY-13442) and exerts a synergistic effect with Paclitaxel (HY-B0015), but may also induce drug resistance by upregulating the SGK3/GSK3β/β-catenin signaling pathway. Alpelisib can be applied to research related to breast cancer, gastric cancer and lipomas associated with PTEN hamartoma tumor syndrome.

HY-111783

AZD-7648	Inhibitor	99.86%
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.

HY-50094

Pictilisib	Inhibitor	99.80%
Pictilisib (GDC-0941) is a potent inhibitor of PI3Kα/δ with an IC₅₀ of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).

HY-180261

GP262	Degrader
GP262 is a PI3K/mTOR PROTAC degrader targeting PI3Kγ, PI3Kα and mTOR with DC₅₀ values of 42.23 nM, 227.4 nM and 45.4 nM, respectively in MDA-MB-231 cells. GP262 induces degradation of p110α and p110γ with a DC₅₀ of 227.4 and 42.23 nM. GP262 efficient modulates the PI3K/AKT/mTOR pathway, achieving degradation through the ubiquitin-proteasome system (UPS). GP262 also exhibits robust antiproliferative activity and induces apoptosis in vitro. GP262 exhibits tumor growth suppression capability and biosafety profile. GP262 can be used for leukemia and triple-negative breast cancer (TNBC) .

HY-118903

PIK-124	Inhibitor
PIK-124 is a thiazolidinone-based PI3Kγ-biased PI3K inhibitor, with an IC₅₀ of 3 nM against PI3Kγ. PIK-124 exhibits cross-reactivity with PI3Kα (IC₅₀ = 23 nM), PI3Kδ (IC₅₀ = 340 nM), PI3KC2α (IC₅₀ = 140 nM) and PI3KC2β (IC₅₀ = 370 nM). PIK-124 is applicable to breast cancer-related research.

HY-120116

AM-8508	Inhibitor
AM-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.

HY-13026

Idelalisib	Inhibitor	99.94%
Idelalisib (CAL-101; GS-1101) is a highly selective and orally bioavailable p110δ inhibitor with an IC₅₀ of 2.5 nM, showing 40- to 300-fold selectivity for p110δ over other PI3K class I enzymes.

HY-70063

Buparlisib	Inhibitor	99.90%
Buparlisib (BKM120; NVP-BKM120) is a pan-class I PI3K inhibitor, with blood-brain barrier permeability. Buparlisib has IC₅₀s of 52, 166, 116 and 262 nM for p110α, p110β, p110δ and p110γ, respectively.

HY-50673

Dactolisib	Inhibitor	99.94%
Dactolisib (BEZ235) is an orally active and dual pan-class I PI3K and mTOR kinase inhibitor with IC₅₀s of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively. Dactolisib (BEZ235) inhibits both mTORC1 and mTORC2.

HY-10681

Gedatolisib	Inhibitor	99.89%
Gedatolisib (PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ, and mTOR with IC₅₀s of 0.4 nM, 5.4 nM and 1.6 nM, respectively. Gedatolisib is equally effective in both complexes of mTOR, mTORC1 and mTORC2.

HY-17044

Duvelisib	Inhibitor	99.88%
Duvelisib (IPI-145) is a selectivite p100δ inhibitor with IC₅₀ of 2.5 nM, 27.4 nM, 85 nM and 1602 nM for p110δ, P110γ, p110β and p110α, respectively.

HY-15346

Copanlisib	Inhibitor	99.35%
Copanlisib (BAY 80-6946) is a potent, selective and ATP-competitive pan-class I PI3K inhibitor, with IC₅₀s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. Copanlisib has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. Copanlisib has superior antitumor activity.

HY-100716

Eganelisib	Inhibitor	99.68%
Eganelisib (IPI549) is a potent and selective PI3Kγ inhibitor with an IC₅₀ of 16 nM. Eganelisib shows >100-fold selectivity over other lipid and protein kinases.

HY-10297

Omipalisib	Inhibitor	99.94%
Omipalisib (GSK2126458) is an orally active and highly selective inhibitor of PI3K with K_is of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM for p110α/β/δ/γ, mTORC1/2, respectively. Omipalisib has anti-cancer activity.

HY-10115

PI-103	Inhibitor	99.82%
PI-103 is a potent PI3K and mTOR inhibitor with IC₅₀s of 8 nM, 88 nM, 48 nM, 150 nM, 20 nM, and 83 nM for p110α, p110β, p110δ, p110γ, mTORC1, and mTORC2. PI-103 also inhibits DNA-PK with an IC50 of 2 nM. PI-103 induces autophagy.

HY-124719

hSMG-1 inhibitor 11j	Inhibitor	99.82%
hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC₅₀ of 0.11 nM. hSMG-1 inhibitor 11j exhibits >455-fold selectivity for hSMG-1 over mTOR (IC₅₀=50 nM), PI3Kα/γ (IC₅₀=92/60 nM) and CDK1/CDK2 (IC₅₀=32/7.1 μM). hSMG-1 inhibitor 11j can be used for the research of cancer.

HY-19962

Paxalisib	Inhibitor	99.51%
Paxalisib (GDC-0084) is a brain penetrant inhibitor of PI3K and mTOR, with K_is of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively.

HY-15346A

Copanlisib dihydrochloride	Inhibitor	99.55%
Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) is a potent, selective and ATP-competitive pan-class I PI3K inhibitor, with IC₅₀s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. Copanlisib dihydrochloride has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. Copanlisib dihydrochloride has superior antitumor activity.

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