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 (236)
Related Products (236)
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PI3Kα-IN-27
0 ImagesCat. No.: HY-178812CAS No.: 2098649-83-1PI3Kα-IN-27 (Compound 50b) is an orally active PI3K-α inhibitor, with an IC50 of 40 nM. PI3Kα-IN-27 effectively inhibits PAK3, p110α, phospho-mTOR and phospho-ERK1/2. PI3Kα-IN-27 induces early Apoptosis. PI3Kα-IN-27 shows anticancer activity against pancreatic cancer, lung cancer, breast cancer.
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PI3Kδ-IN-12
0 ImagesCat. No.: HY-149235PI3Kδ-IN-12 (compound 13) is a PI3Kδ inhibitor (pIC50 = 5.8), with pKi values of 8.0/6.5/6.4/6.7 for PI3Kδ/γ/β/α, respectively. PI3Kδ-IN-12 can be used in the study of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
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PI3Kα-IN-32
0 ImagesCat. No.: HY-183285CAS No.: 3057582-20-1
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PROTAC PI3Kδ degrader-1
0 ImagesCat. No.: HY-176239PROTAC PI3Kδ degrader-1 is a Lysine-targeted covalent PI3Kδ PROTAC degrader with a DC50 of 3.98 nM. PROTAC PI3Kδ degrader-1 has a potent antiproliferative activity and selective PI3Kδ inhibition (IC50: 8 nM). PROTAC PI3Kδ degrader-1 also significantly degrades p-AKT, induces cell cycle arrest in G1 phase and prompts cell apoptosis and autophagy. PROTAC PI3Kδ degrader-1 effectively inhibits the tumor growth in SU-DHL-6 xenograft mice model.
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PI3Kδ-IN-21
0 ImagesCat. No.: HY-158688CAS No.: 3048633-11-7PI3Kδ-IN-21 (Compound 31) is a selective inhibitor for phosphoinositide 3-kinases δ (PI3Kδ), with an IC50 of 13.6 nM. PI3Kδ-IN-21 inhibits proliferation and differentation of T cells through PI3K/AKT/mTOR signaling pathway. PI3Kδ-IN-21 exhibits good pharmacokinetic characters in rat model, and attenuates the experimental autoimmune encephalomyelitis in myelin oligodendrocyte glycoprotein (MOG)-induced EAE model.
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ST-168
0 ImagesCat. No.: HY-120281CAS No.: 2126038-25-1ST-168 is an orally active MEK/PI3K inhibitor with an IC50 of 182 nM against MEK1 and IC50 values of 69.2, 41.7, 1482 and 2293 nM against PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ respectively. ST-168 completely inhibits the phosphorylation of ERK1/2 and AKT and induces cancer cell death in a 3D tumor sphere model. ST-168 demonstrates significant antitumor effects in the A375 melanoma mouse model. ST-168 improves the ocular toxicity profile of MEK inhibitors, showing lower caspase activation levels, indicating reduced apoptosis induction. ST-168 can be used in melanoma research.
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PI3Kδ-IN-24
0 ImagesCat. No.: HY-175002CAS No.: 3051829-20-7PI3Kδ-IN-24 is a selective PI3Kδ inhibitor (IC50 = 0.1 nM). PI3Kδ-IN-24 exhibits significant antiproliferative effects against PI3Kδ-overexpressing cancer cell lines. PI3Kδ-IN-24 reduces p-AKT levels and induces cell cycle arrest and apoptosis in tumor cells. PI3Kδ-IN-24 is useful in cancer research, such as diffuse large B-cell lymphoma (DLBCL).
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PI3Kα-IN-14
0 ImagesCat. No.: HY-157125CAS No.: 3026856-46-9PI3Kα-IN-14 (compound F8) is a selective PI3Kα inhibitor with an IC50 of 0.14 nM. PI3Kα-IN-14 induces a great decrease in mitochondrial membrane which caused cell cycle arrest at G1 phase and apoptosis in U87-MG cells. PI3Kα-IN-14 shows significant anti-proliferative activities against three tumor-derived cell lines (PC-3: IC50 of 0.28 μM; HCT-116: IC50 of 0.57 μM; and U87-MG: IC50 of 1.37 μM).
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PI3Kα-IN-20
0 ImagesCat. No.: HY-163361CAS No.: 228999-57-3PI3Kα-IN-20 (compound 2) is a selective PI3Kα inhibitor.
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DHW-208
0 ImagesCat. No.: HY-128633CAS No.: 2269470-35-9PI3K-IN-4 is a potent Pan-PI3K inhibitor. PI3K-IN-4 has high activity for three PI3K isoforms with the IC50 values of picomole. PI3K-IN-4 shows superior inhibitory activity against PI3Kα (IC50 = 0.20 nM), PI3Kβ (IC50 = 2.99 nM), PI3Kδ (IC50 = 0.48 nM) and PI3Kγ (IC50 = 0.58 nM) and has no significant activity against EGFR. PI3K-IN-4 inhibits cancer cell growth though PI3K/Akt signaling pathway, leading to the inhibition of colony formation and the induction of apoptosis. PI3K-IN-4 can be used for lung, colon and breast cancer research.
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PI3Kα-IN-23
0 ImagesCat. No.: HY-163501CAS No.: 3033941-92-0PI3Kα-IN-23 (Compound 9) is an inhibitor of PI3Ka H1047R.
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PI3K/HDAC-IN-4
0 ImagesCat. No.: HY-172889CAS No.: 3085191-45-0PI3K/HDAC-IN-4 (Compound 31f) is a PI3K/HDAC dual inhibitor (IC50: 0.2μM). PI3K/HDAC-IN-4 shows high selectivity for HDAC1-3 (IC50 values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively). PI3K/HDAC-IN-4 is a potent PIK3 inhibitor with IC50 values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. PI3K/HDAC-IN-4 significantly induces tumor cell apoptosis by simultaneously inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. PI3K/HDAC-IN-4 exhibits potent antiproliferative activity in a variety of tumor cell lines (e.g., MV4-11, Jeko-1, HL60, and MCF-7, with IC50 values of 0.2, 0.9, 0.8, and 1.5 μM, respectively). PI3K/HDAC-IN-4 can be used in the study of lymphoma and leukemia.
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CC-11
0 ImagesCat. No.: HY-179457CAS No.: 3079942-94-9CC-11 is an orally active small molecule drug conjugate (SMDC) that links the PI3K/mTOR inhibitor with the extracellular heat shock protein 90 (EHSP90) targeting ligand through a cleavable linker. CC-11 exhibits strong HSP90 binding activity (IC50 = 15 nM) and inhibits PI3Kα kinase activity (IC50 = 0.54 nM). CC-11 has anti-proliferative activity against colon cancer cells. CC-11 shows significant efficacy in the HCT-116 xenograft tumor model. CC-11 can be used for research on colon cancer.
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SJY26
0 ImagesCat. No.: HY-178485SJY26 is a PI3K/HDAC dual-target inhibitor with IC50s of 0.59 nM (PI3Kα and PI3Kδ), 2.02 nM (PI3Kγ), 12.69 nM (PI3Kβ) and 114 nM (HDAC1). SJY26 exhibits potent broad-spectrum anti-proliferative activity, and is particularly sensitive to Jurkat and PC9R cells. SJY26 inhibited the migration of PC9R cells, arrested the cell cycle and induced cell apoptosis. SJY26 reduces AKT phosphorylation, and decreases histone H3 deacetylation (Ac-H3). SJY26 can be used for the studies of non-small cell lung cancer and leukemia.
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SRX3212
0 ImagesCat. No.: HY-183922CAS No.: 2735720-80-4SRX3212 is a potent PI3Kα/BRD4 inhibitor with human IC50 values of 22 nM, 3.7 nM, and 32 nM for PI3Kα, BRD4BD1, and BRD4BD2, respectively. SRX3212 inhibits PI3K kinase activity and blocks acetyllysine binding function of BRD4BD1 and BRD4BD2. SRX3212 can be used for the research of mantle cell lymphoma, colon carcinoma, neuroblastoma, prostate cancer[1].
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VVD-844
0 ImagesCat. No.: HY-183741CAS No.: 3080226-63-4VVD-844 is an orally active covalent inhibitor of PI3Kα, which inhibits Pl3Kα/p110α interaction with an IC50 of 4 nM. VVD-844 covalently binds to Cys242 in the RAS binding domain of p110α, blocking RAS-p110α interaction and inhibiting PI3Kα activity. VVD-844 inhibits PI3Kα signaling activation in HER2-overexpressing cells via a RAS-independent mechanism. VVD-844 suppresses tumor growth in mouse. VVD-844 can be used for the research of cancers.
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PI3Kα-IN-8
0 ImagesCat. No.: HY-147983CAS No.: 2315320-24-0PI3Kα-IN-8 (Compound 9g) is a selective PI3Kα inhibitor with an IC50 of 0.012 μM. PI3Kα-IN-8 increases intracellular reactive oxygen species level, decreases mitochondrial membrane potential and induces apoptosis.
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PI3Kα-IN-1
0 ImagesCat. No.: HY-124647CAS No.: 2100855-80-7
