2. Signaling Pathways
  3. PI3K/Akt/mTOR
  4. PI3K
  5. PI3KC2γ Isoform

PI3KC2γ

PI3KC2γ is a liver-enriched class II PI3K isoform that generates endosomal PI(3,4)P2 during insulin signaling[1]. Mechanistically, insulin triggers PI3KC2γ association with Rab5-GTP and recruitment to Rab5-positive early endosomes, where this lipid pool supports delayed and sustained Akt2 activation[1]. Loss of PI3KC2γ selectively reduces Akt2 activation without affecting Akt1, S6K, or FoxO1-3 phosphorylation, thereby impairing glycogen synthase activity and hepatic glycogen accumulation[1]. In mouse models, PI3KC2γ deficiency promotes hyperlipidemia, adiposity, insulin resistance, and high-fat-diet-associated fatty liver[1]. Human genetic evidence also links PIK3C2G polymorphisms with type 2 diabetes in a Japanese population[2]. Compared with ubiquitous PI3K-C2α and PI3K-C2β, PI3KC2γ shows a more restricted liver-parenchyma pattern, making isoform distinction essential in pathway design[1]. For experimental applications, early lead compounds and newer selective PI3KC2γ inhibitors provide tools to interrogate glycogen metabolism and class II PI3K isoform biology[3][4].

PI3KC2γ Related Products (4):

Cat. No. Product Name Effect Purity
  • HY-15837
    SAR-260301
    		Inhibitor 99.95%
    SAR-260301 is an orally available and selective PI3Kβ inhibitor with an IC50 of 23 nM.
  • HY-112443
    AZD3458
    		Inhibitor 99.71%
    AZD3458 is a potent and remarkably selective PI3Kγ inhibitor with pIC50s of 9.1, 5.1, <4.5, and 6.5 for PI3Kγ, PI3Kα, PI3Kβ, and PI3Kδ, respectively.
  • HY-19798
    PI4KIIIbeta-IN-9
    		Inhibitor 99.18%
    PI4KIIIbeta-IN-9 is a potent PI4KIIIβ inhibitor with an IC50 of 7 nM. PI4KIIIbeta-IN-9 also inhibits PI3Kδ and PI3Kγ with IC50s of 152 nM and 1046 nM, respectively.
  • HY-178371
    PI3KC2γ-IN-1
    		Inhibitor
    PI3KC2γ-IN-1 (Compound 23) is an orally active and selective PI3KC2γ inhibitor (IC50 = 4 nM). PI3KC2γ-IN-1 downregulats the Akt2-glycogen synthase (GS) signaling pathway, ultimately inhibiting the conversion of glucose to glycogen and reduces excessive glycogen accumulation in the liver. PI3KC2γ-IN-1 can significantly inhibit insulin-induced PI(3,4)P2 accumulation in both primary hepatocytes and HepG2 liver cancer cells. PI3KC2γ-IN-1 can be used for the study of glycogen storage diseases (GSDs).