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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DHW-221
0 ImagesCat. No.: HY-130133CAS No.: 2378831-21-9DHW-221 is a potent orally active dual PI3K/mTOR inhibitor, exhibiting low nanomolar potency against all four Class I PI3K isoforms and mTOR (PI3Kα, IC50 = 0.50 nM; PI3Kβ, IC50 = 1.9 nM; PI3Kγ, IC50 = 1.8 nM; PI3Kδ, IC50 = 0.74 nM; mTOR, IC50 = 3.9 nM). DHW-221 exerts antitumor effects by blocking the PI3K/Akt/mTOR pathway and inducing mitochondrial apoptosis and paraptosis (via Endoplasmic Reticulum (ER) stress and MAPK signaling) and arrests cell cycle, thereby inhibiting cell migration, invasion and angiogenesis. DHW-221 inhibits tumor growth in both the A549/Taxol (HY-B0015) and the HCC827 xenograft mouse models. DHW-221 can be used for non-small cell lung cancer (NSCLC), colon and breast cancer research.
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mTOR-IN-31
0 ImagesCat. No.: HY-187134CAS No.: 1144075-32-0mTOR-IN-31 is a selective mTOR inhibitor with an IC50 of 0.9 nM. mTOR-IN-31 inhibits the proliferation of prostate cancer cells. mTOR-IN-31 is applicable for cancer-related research.
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PI3K-IN-38
0 ImagesCat. No.: HY-150034CAS No.: 1382979-64-7PI3K-IN-38 (compound 123) is an orally active PI3K inhibitor with IC50 of 0.541 µM (PI3K-α). PI3K-IN-38 shows activities of anticancer and anti-inflammatory, which inhibis tumor growth in vivo.
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PI3Kα-IN-26
0 ImagesCat. No.: HY-176281PI3Kα-IN-26 (Compound 11e) is a PI3Kα inhibitor with an IC50 of 75.31 nM. PI3Kα-IN-26 has a broad-spectrum anticancer activity, such as leukemia, colon and breast cancer, without significant cytotoxic effect on the normal Vero cells (mean IC50s of 2.74, 3.50, 3.34 and 85.29 μM, respectively).
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LNP23
0 ImagesCat. No.: HY-189462CAS No.: 3136664-01-9LNP23 is a selective PI3Kα inhibitor with an IC50 of 5.15 nM. LNP23 inhibits PI3K/AKT signaling and induces apoptosis and G1 phase arrest in MCF-7 cells. LNP23 also inhibits cancer cell proliferation, colony formation, and migration. LNP23 can be used for breast cancer and lung adenocarcinoma research.
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NVP-CLR457
0 ImagesCat. No.: HY-146260CAS No.: 1453082-52-4NVP-CLR457 (compound 40) is an orally active, potent and balanced pan-class I PI3K inhibitor. NVP-CLR457 shows a clear dose-dependent PK/PD/efficacy relationship. NVP-CLR457 has antitumor activity.
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PI3Kα/CDK7-IN-1
0 ImagesCat. No.: HY-187454PI3Kα/CDK7-IN-1 is a dual-target hybrid inhibitor of PI3Kα and CDK7, with IC50 values of 87.9 nM and 638 nM, respectively. PI3Kα/CDK7-IN-1 acts as a cytotoxic agent and cell death inducer that triggers apoptotic death in cancer cells. PI3Kα/CDK7-IN-1 can be used in cancer research such as colorectal cancer.
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PI3K-IN-34
0 ImagesCat. No.: HY-147899CAS No.: 2458163-94-3
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PI3K/HDAC-IN-2
0 ImagesCat. No.: HY-146159CAS No.: 2361418-65-5PI3K/HDAC-IN-2 is a potent dual PI3K/HDAC inhibitor with IC50s of 226 nM, 279 nM, 467 nM, 29 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively, and IC50s of 1.3 nM, 3.4 nM, 972 nM, 17 nM, 12 nM for HDAC1, HDAC2, HDC4, HDAC6, HDAC8, respectively. PI3K/HDAC-IN-2 exhibits PI3Kδ and class I and IIb HDAC selectivity. PI3K/HDAC-IN-2 has remarkable anticancer effects.
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PI3Kα-IN-31
0 ImagesCat. No.: HY-182946CAS No.: 3115133-30-4PI3Kα-IN-31 is an orally active and selective PI3Kα inhibitor. PI3Kα-IN-31 shows potent preference for mutant PI3Kα over wild-type PI3Kα. PI3Kα-IN-31 exerts antiproliferative effects in PI3Kα-mutant cancer cells. PI3Kα-IN-31 suppresses tumor growth in xenograft models. PI3Kα-IN-31 can be used for the research of breast cancer.
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Pabgraminone C
0 ImagesCat. No.: HY-184119CAS No.: 3061276-55-6Synonyms: IM502Pabgraminone C (IM502) is a Fungal metabolite and PI3Kγ inhibitor with an IC50 of 61.7 nM against PI3Kγ. Pabgraminone C shifts the STAT signaling pathway in cells from an immunosuppressive STAT3/STAT6-dominant profile to an immunostimulatory STAT1/STAT2-dominant profile, driving cells toward a pro-inflammatory phenotype. Pabgraminone C reprograms cells from an immunosuppressive state to an immunostimulatory state, reversing their suppressive effect on anti-tumor immunity. Pabgraminone C inhibits established tumor growth and metastasis across multiple cancer types. Pabgraminone C overcomes resistance to PD-1 checkpoint blockade strategies. Pabgraminone C can be used in research related to liver cancer, melanoma, and colorectal cancer.
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PI3Kα-IN-5
0 ImagesCat. No.: HY-144295CAS No.: 2237953-19-2PI3Kα-IN-5 (compound 6 ab) is a potent PI3Kα/mTOR inhibitor, with an IC50 of 0.7 nM and 3.3 nM, respectively. PI3Kα-IN-5 can be used for the research of colorectal cancer.
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PI3Kα-IN-29
0 ImagesCat. No.: HY-179623PI3Kα-IN-29 is a potent, orally active and selective PI3Kα with an IC50 of 2.5 nM. PI3Kα-IN-29 exhibits >400-fold selectivity over PI3Kβ/δ/γ/mTOR. PI3Kα-IN-29 selectively degrades the H1047R mutant p110α protein and inhibits PI3Kα kinase activity. PI3Kα-IN-29 suppresses PI3K/AKT/mTOR signaling, induces G1 arrest, and inhibits migration. PI3Kα-IN-29 inhibits tumor growth in a T47 mouse model. PI3Kα-IN-29 can be used for the research of breast cancer.
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Anticancer agent 331
0 ImagesCat. No.: HY-184487Anticancer agent 331 is an anticancer agent with favorable cell permeability and limited blood-brain barrier penetration. Anticancer agent 331 forms stable long-acting complexes with TNF-α, PI3K p110α, AKT1 and mTOR, and exerts cytotoxic effects on cancer cells. Anticancer agent 331 can be used in the research of colorectal cancer.
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PI3Kα-IN-28
0 ImagesCat. No.: HY-178984CAS No.: 3095278-75-1PI3Kα-IN-28 (Compound 23) is an efficient dual targeted PI3K/BRD4 inhibitor. PI3Kα-IN-28 can inhibit the proliferation of various cells, such as KYSE180 and KYSE450 cells. PI3Kα-IN-28 can concentration dependently inhibit migration and colony formation, induce G0/G1 phase arrest, significantly inhibit DNA synthesis, and significantly increase the proportion of senescent cells. PI3Kα-IN-28 can inhibit the expression of p-AKT and c-Myc and activate the AMPK-p27 pathway. PI3Kα-IN-28 can be used for research on cancers such as esophageal cancer.
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eALM1192
0 ImagesCat. No.: HY-189486CAS No.: 3134761-90-0eALM1192 is a selective mTOR kinase inhibitor (IC50 = 2.3 nM) that also inhibits DNA-PK (IC50 = 84 nM), PI3Kα, and PKN3, with 37-fold selectivity for mTOR over DNA-PK. eALM1192 exhibits antiproliferative activity against cancer cell lines and colorectal cancer cell lines. eALM1192 can be used for colorectal cancer research.
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PI3K/mTOR-IN-20
0 ImagesCat. No.: HY-180556PI3K/mTOR-IN-20 is a selective dual PI3K/mTOR inhibitor. PI3K/mTOR-IN-20 demonstrates nanomolar antiproliferative effects with IC50s of 0.380 and 0.090 μM for MRC-5 and Mlg2908 cells. PI3K/mTOR-IN-20 reduces Ashcroft scores, hydroxyproline content, collagen deposition, and downregulates fibrosis-related proteins, while restoring lung architecture in a Bleomycin-induced pulmonary fibrosis model. PI3K/mTOR-IN-20 shows a favorable safety profile with steady weight recovery and no distinct liver or kidney toxicity. PI3K/mTOR-IN-20 can be used for fetal lung fibroblasts research.
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PI3Kα-IN-13
0 ImagesCat. No.: HY-156018CAS No.: 2955529-67-4PI3Kα-IN-13 (Compound 18a) is a PI3Kα inhibitor (IC50: 2.5 nM). PI3Kα-IN-13 induces tumor cell apoptosis. PI3Kα-IN-13 inhibits cancer cell proliferation with IC50s of 0.75 μM (MCF-7), 3.79 μM (HCT-116), 13.71 μM (MDA-MB-231), 9.85 μM (SW620), respectively. PI3Kα-IN-13 inhibits tumor cell colony formation, migration and invasion.
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PI3K-IN-58
0 ImagesCat. No.: HY-172886CAS No.: 3067572-78-2PI3K-IN-58 (Compound 17f) is a PI3Kα inhibitor (IC50: 0.039 μM). PI3K-IN-58 exhibits significant antiproliferative effects on PC-3, 22RV1, MDA-MB-231 and MDA-MB-453 cell lines with IC50s of 3.48 μM, 1.06 μM, 2.21 μM and 0.93 μM, respectively. PI3K-IN-58 induces apoptosis by downregulating the expression levels of anti-apoptotic proteins Bcl-XL and Bcl-2 and upregulating the expression of anti-apoptosis protein BAX. PI3K-IN-58 can be used in PI3K-targeted cancer research.
