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 (237)
Related Products (237)
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AMG 511
0 ImagesAMG 511 is a potent and orally available pan inhibitor of class I PI3Ks, with Kis of 4 nM, 6 nM, 2 nM and 1 nM for PI3Kα, β, δ and γ, respectively. AMG 511 significantly suppresses PI3K signaling that is indicated by p-Akt (Ser473) decrease. AMG 511 exhibits anti-tumor activity in mouse glioblastoma xenograft model.
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PI3Kγ inhibitor AZ2
0 ImagesPI3Kγ inhibitor AZ2 is a highly selective PI3Kγ inhibitor (The pIC50 value for PI3Kγ is 9.3). PI3Kγ inhibitor AZ2 can be used for the research of inflammatory and immune diseases.
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PKI-179
0 ImagesPKI-179 is a potent and orally active dual PI3K/mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo.
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Izorlisib
0 ImagesSynonyms: CH5132799Izorlisib (CH5132799) is an orally active, selective Class I PI3K inhibitor with an IC50 value of 14 nM against PI3Kα. Izorlisib specifically inhibits Class I PI3K (particularly PI3Kα and its mutants) and blocks the PI3K/Akt/mTOR pathway; this leads to cell cycle arrest at the G1 phase and apoptosis without triggering feedback activation of Akt by competitively binding to the ATP-binding site of PI3K. Izorlisib can be used in research on cancers harboring PIK3CA mutations or PTEN loss (such as breast, ovarian, prostate, and endometrial cancers).
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PF-06843195
0 ImagesPF-06843195 is a highly selective PI3Kα inhibitor with an IC50 of 18 nM in Rat1 fibroblasts. The Kis of PF-06843195 for PI3Kα and PI3Kδ in biochemical kinase assay are less than 0.018 nM and 0.28 nM, respectively. PF-06843195 has great suppression of the PI3K/mTOR signaling pathway and durable antitumor efficacy.
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Brevianamide F
0 ImagesSynonyms: Cyclo(L-Pro-L-Trp)Brevianamide F (Cyclo(L-Pro-L-Trp)) is a mycotoxin isolated from Colletotrichum gloeosporioides, with antibacterial activity. Brevianamide F shows potent PI3Kα inhibitory activity with an IC50 of 4.8 μM.
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Alpelisib hydrochloride
0 ImagesSynonyms: BYL-719 hydrochlorideAlpelisib (BYL-719) hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride can be applied to research related to breast cancer, gastric cancer and lipomas associated with PTEN hamartoma tumor syndrome.
