PI3Kα
PI3Kα (p110α), encoded by PIK3CA, is a class IA phosphoinositide 3-kinase catalytic subunit that forms a heterodimer with p85 regulatory proteins and catalyzes the phosphorylation of phosphatidylinositol-(4,5)-bisphosphate to generate phosphatidylinositol-(3,4,5)-trisphosphate, thereby regulating cell growth, proliferation, survival, migration, and metabolic signaling[1][2]. Mechanistically, PI3Kα is a central component of the PI3K-AKT-mTOR signaling axis and functions downstream of receptor tyrosine kinases and RAS proteins to amplify intracellular growth and survival pathways[3][4]. Dysregulation of this pathway is among the most common molecular events in human cancer, and activating mutations in PIK3CA promote tumor initiation, progression, and therapeutic resistance through sustained PI3K signaling[3][5]. In disease models, disruption of the RAS-PI3Kα interaction suppresses tumor growth and angiogenesis, highlighting the importance of PI3Kα-dependent signaling in oncogenic processes[4]. Compared with related class I PI3K isoforms, p110α and p110β are broadly expressed across tissues, whereas p110δ is predominantly expressed in leukocytes, indicating distinct physiological functions and therapeutic opportunities among isoforms[6]. Furthermore, PTEN-deficient tumors frequently depend on p110β activity, emphasizing a biologically important distinction between PI3Kα- and PI3Kβ-driven signaling networks[2]. For experimental and translational applications, isoform-selective PI3Kα inhibitors, including alpelisib, have been developed to target PIK3CA-driven malignancies, making PI3Kα a major focus of precision oncology research[5].
References:
- [1]. PI3Kα gene information from NCBI.
- [2]. Mazloumi Gavgani F, et al. Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer. Int J Mol Sci. 2018 Dec 7;19(12):3931. [Content Brief]
- [3]. Wang Y, et al. Oncogenic activation of PIK3CA in cancers: Emerging targeted therapies in precision oncology. Genes Dis. 2024 Sep 10;12(2):101430. [Content Brief]
- [4]. Czyzyk D, et al. Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation. Nat Commun. 2025 Jan 9;16(1):525. [Content Brief]
- [5]. Thorpe LM, et al. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer. 2015 Jan;15(1):7-24. [Content Brief]
- [6]. Wikipedia.
- [7]. Wikipedia.
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PI3Kα Related Products (240)
Related Products (240)
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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.
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PI3K/HDAC-IN-1
0 ImagesCat. No.: HY-128582CAS No.: 2361418-52-0
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PIK-124
0 ImagesCat. No.: HY-118903CAS No.: 711025-68-2
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PI3K-IN-6
0 ImagesCat. No.: HY-101115CAS No.: 1842380-77-1PI3K-IN-6 (compound 20a) is an oral active and highly selective phosphoinositide 3-kinase (PI3K) β/δ inhibitor, with IC50 values of 7.8 nM/5.3 nM for PI3K β/δ, respectively. PI3K-IN-6 (compound 20a) has potential top treat phosphatase and tensin homolog (PTEN) feficient tumors.
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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.
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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.
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PI3Kα-IN-6
0 ImagesCat. No.: HY-147767CAS No.: 2272894-14-9PI3Kα-IN-6 (Compound 5b) is a PI3Kα inhibitor. PI3Kα-IN-6 exhibits anticancer potential and no toxicity in normal cells. PI3Kα-IN-6 increases generation of ROS, reduces mitochondrial membrane potential (MMP) and induces apoptosis.
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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.
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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.
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PI3K-IN-33
0 ImagesCat. No.: HY-147898CAS No.: 2458163-92-1
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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.
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PI3Kα-IN-25
0 ImagesCat. No.: HY-172139PI3Kα-IN-25 (Compound Djh1) is a selective PI3Kα inhibitor. PI3Kα-IN-25 can be used in triple-negative breast cancer research.
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D-106669
0 ImagesCat. No.: HY-111058CAS No.: 938444-93-0
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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.
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EGFR-IN-217
0 ImagesCat. No.: HY-189142EGFR-IN-217 is an ATP-competitive EGFR kinase inhibitor, with an IC50 of 60.7 nM against EGFR. EGFR-IN-217 exhibits kinase inhibitory activity against PI3K-α and mTOR. EGFR-IN-217 upregulates pro-apoptotic factors including P53, Bax, PUMA, and caspase-7, -8 and -9, and downregulates the anti-apoptotic protein BCL-2, thereby inducing cell apoptosis and cycle arrest. EGFR-IN-217 shows tumor growth inhibitory effects in the solid Ehrlich ascites carcinoma xenograft mouse model. EGFR-IN-217 can be applied in the research of solid Ehrlich ascites carcinoma, hepatocellular carcinoma, and breast cancer.
