Home PI3K/Akt/mTOR PI3K

PI3K inhibitors/activators

Phosphatidylinositol 3-kinase (PI 3-kinase or PI3K) is a famous target which is the upstream of akt because PI3K can activate Akt when PI3K is activated by growth factors including EGF, IGF, TGF-α and so on. The activation Class IA PI3Ks by growth factors is receptor tyrosine kinase (RTK)-dependent activation. Class IB PI3K is primarily regulated by small G-proteins such as Ras. PI3K is a key enzyme involved in cell processes, apoptosis and cancer. PI3K with mTOR, akt and MEK plays a key role in cancer.  [show the full text]

Other PI3K/Akt/mTOR Related Inhibitors

MEK p38 MAPK Raf JNK S6 Kinase MNK TOPK Mixed Lineage Kinase TAK1 KLF MAPKAPK2

Isoform-selective Products

Cat.No. Product Name Information Product Use Citations Product Validations
S1105 LY294002 LY294002 (SF 1101, NSC 697286) is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation. It not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family. This compound also inhibits CK2 with IC50 of 98 nM. It is a non-specific DNA-PKcs inhibitor and activates autophagy and apoptosis.
Gut, 2025, gutjnl-2025-335163
Cell Mol Immunol, 2025, 22(5):541-556
Nat Commun, 2025, 16(1):1661
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S2226 CAL-101 (Idelalisib) Idelalisib (CAL-101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy.
Cell Rep Med, 2025, S2666-3791(25)00102-8
J Immunother Cancer, 2025, 13(4)e010684
EMBO Rep, 2025, 10.1038/s44319-025-00444-2
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S2247 Buparlisib (BKM120) Buparlisib (BKM120, NVP-BKM120) is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Buparlisib induces apoptosis. Phase 2.
Nat Commun, 2025, 16(1):1237
Cell Rep Med, 2025, 6(9):102356
Cell Death Dis, 2025, 16(1):210
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S2814 Alpelisib (BYL719) Alpelisib (BYL719) is a potent and selective PI3Kα inhibitor with IC50 of 5 nM in a cell-free assay, and minimal effect on PI3Kβ/γ/δ. This compound is in Phase 2.
Signal Transduct Target Ther, 2025, 10(1):92
Nat Genet, 2025, 57(9):2192-2202
Drug Resist Updat, 2025, 81:101251
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S7028 Duvelisib (IPI-145) Duvelisib (IPI-145, INK1197) is a novel and selective PI3K δ/γ inhibitor with Ki and IC50 of 23 pM/243 pM and 1 nM/50 nM in cell-free assays. This compound is highly selective for PI3K δ/γ than other protein kinases. Phase 3.
Cell Rep Med, 2025, S2666-3791(25)00102-8
Cell Mol Life Sci, 2025, 82(1):152
bioRxiv, 2025, 2025.04.26.650783
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S7865 740 Y-P (PDGFR 740Y-P) 740 Y-P (PDGFR 740Y-P, 740YPDGFR) is a cell-permeable phosphopeptide activator of PI3K.
Cell Death Dis, 2025, 16(1):538
Biochim Biophys Acta Mol Basis Dis, 2025, 1871(7):167920
World J Diabetes, 2025, 16(5):102196
S7682 SAR405 SAR405 is a low-molecular-mass kinase inhibitor of PIK3C3/Vps34 (KD 1.5 nM) showing high selectivity and not be active up to 10 μM on class I and class II PI3Ks as well as on mTOR. This compound prevents autophagy and synergizes with MTOR (mechanistic target of rapamycin) inhibition in tumor cells.
Cell Res, 2025, 10.1038/s41422-025-01085-9
Nat Cell Biol, 2025, 27(9):1448-1464
Autophagy, 2025, 21(7):1523-1543
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S2628 Gedatolisib (PKI-587) Gedatolisib (PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ and mTOR with IC50 of 0.4 nM, 5.4 nM and 1.6 nM in cell-free assays, respectively. This compound is currently in Phase 2.
PLoS One, 2025, 20(6):e0324443
bioRxiv, 2025, 2025.01.10.632413
Nat Commun, 2024, 15(1):686
Verified customer review of Gedatolisib (PKI-587)
S8330 Eganelisib (IPI-549) A potent inhibitor of PI3K-γ with >100-fold selectivity over other lipid and protein kinases, Eganelisib (IPI-549) has a biochemical IC50 for PI3K-γ of 16 nM.
J Control Release, 2025, 387:114189
MedComm (2020), 2025, 6(8):e70223
Innate Immun, 2025, 31:17534259251343377
S1118 XL147 analogue XL147 analogue (SAR245408) is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39 nM/36 nM/23 nM in cell-free assays, less potent to PI3Kβ. This compound induces apoptosis. Phase 1/2.
J Pers Med, 2022, 12(2)258
Hum Cell, 2022, 10.1007/s13577-022-00671-y
Hum Cell, 2021, 10.1007/s13577-021-00579-z
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S8674 GO-203 TFA GO-203 is a D-amino acid cell-penetrating peptide inhibitor of MUC1-C dimerization and thereby its oncogenic function.
Clin Cancer Res, 2025, 31(24):5246-5260
JCI Insight, 2025, 10(14)e190924
Cell Death Discov, 2025, 11(1):372
S8163 Paxalisib (GDC-0084) Paxalisib (GDC-0084, RG7666) is a brain penetrant inhibitor of PI3K and mTOR with Kiapp values of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR.
Cell Death Dis, 2025, 16(1):210
Cell Death Discov, 2023, 9(1):172
Cell Death Discov, 2023, 9(1):172
S8668 GDC-0077 (Inavolisib) Inavolisib (GDC-0077, RG6114, RO-7113755) is a potent selective inhibitor of PI3K alpha (PI3Kα) with an IC50 of 0.038 nM. GDC-0077 is >300-fold more selective for PI3K alpha over the other class I PI3K isoforms (beta, delta, and gamma) and >2000-fold more selective over PIK family members. GDC-0077 binds to the ATP binding site of PI3K and inhibits the phosphorylation of PIP2 to PIP3.
Cell Rep Med, 2025, S2666-3791(25)00102-8
Int J Mol Sci, 2025, 26(12)5844
Nature, 2024, 10.1038/s41586-024-08031-6
S2391 Quercetin (Sophoretin) Quercetin, a natural flavonoid present in vegetables, fruit and wine, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC50 of 2.4-5.4 μM. Quercetin induces mitophagy, apoptosis and protective autophagy. Phase 4.
Alzheimers Res Ther, 2025, 17(1):176
Cell Mol Life Sci, 2025, 82(1):164
Virol Sin, 2025, S1995-820X(25)00102-6
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E1815 Tersolisib (STX-478) Tersolisib (STX-478) is a highly potent, mutant-selective, allosteric inhibitor of PI3Kα, that selectively targets prevalent mutant forms of PI3Kα. It demonstrates strong efficacy against common PI3Kα helical- and kinase-domain mutations, including the H1047R variant, with an IC50 value of 9.4 nmol/L. STX-478 exhibits 14-fold greater selectivity for mutant PI3Kα over the wild-type form. It spares metabolic dysfunction and improves therapeutic response in PI3Kα-Mutant Xenografts.
S2638 NU7441 (KU-57788) NU7441 (KU-57788) is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM. It also inhibits mTOR and PI3K with IC50 of 1.7 μM and 5 μM in cell-free assays, respectively, and reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage.
Nat Cell Biol, 2025, 27(1):59-72
Trends Biotechnol, 2025, S0167-7799(25)00314-2
Nat Commun, 2025, 16(1):997
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S2759 Fimepinostat (CUDC-907) Fimepinostat (CUDC-907) is a dual PI3K and HDAC inhibitor targeting PI3Kα and HDAC1/2/3/10 with IC50 values of 19 nM and 1.7 nM/5 nM/1.8 nM/2.8 nM, respectively. This compound induces cell cycle arrest and apoptosis in breast cancer cells. Phase 1.
Cell Death Discov, 2025, 11(1):172
J Am Heart Assoc, 2025, 14(1):e037400
Viruses, 2024, 16(5)775
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S8045 KU-0060648 KU-0060648 is a dual inhibitor of DNA-PK and PI3Kα, PI3Kβ, PI3Kδ with IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively, less inhibition of PI3Kγ with IC50 of 0.59 μM.
Breast Cancer Res, 2022, 24(1):41
Biomedicines, 2021, 9(5)579
Chembiochem, 2021, 22(12):2177-2181
Verified customer review of KU-0060648

Signaling Pathway Map

Phosphatidylinositol 3-kinases (PI3Ks) are a family of lipid kinases whose biological function is to phosphorylate the 3-hydroxyl group of phosphoinositide. It is proved that PI3K-dependent signaling pathway contributes to many cellular processes such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which might be involved in oncogenesis under certain situation[1]. When a growth factor or ligand binds to the tyrosine kinase receptors (RTK), the PI3K is activated by G protein-coupled receptors[2]. PI3Ks family is generally divided into Class I, Class II, and Class III according to their primary structure, regulation, and in vitro lipid substrate specificity[2]. Class I PI3Ks are heterodimeric molecules composed of a regulatory subunit (p85) and a catalytic subunit (p110). The regulatory subunit of PI3K could be further divided in to six subtypes: p85-α, p85-β, p55-γ, p150,p101 and p87. P85α is the most highly expressed regulatory subunit than the others. And the catalytic subunit could also further divided into four subtypes: p110-α, p110-β, p110-γ and p110-δ. The α and β isoforms of p110 are expressed in all kinds of cells, whereas δ is only found in leukocytes. The regulatory subunit p101 and catalytic subunit p110γ comprise a complex which is classified as Class IB PI3K. Other collocations of regulatory and catalytic subunits are called Class IA PI3Ks. However, class II is structurally different from Class I. There are three catalytic isoforms of Class II PI3Ks: PI3K-C2α, -C2β, and -C2γ, but no regulatory subunit. Class III is structurally similar to Class I for the reason that it is composed of a catalytic (Vps34) and a regulatory subunit (p150). Functionally, class I PI3Ks catalyze the production of phosphatidylinositol 3-phosphate (PtdIns-3,4-P), phosphatidylinositol (3,4)-bisphosphate (PtdIns-3,4-P2), and phosphatidylinositol (3,4,5)-triphosphate (PtdIns-3,4,5-P3). Class II is related to the production of PtdIns-3-P and PtdIns-3,4-P2, while class III specifically catalyzes the production of PtdIns-3,4-P2 [3-5].