PI3K (Phosphoinositide 3-kinase), via phosphorylation of the inositol lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), forms the second messenger molecule phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) which recruits and activates pleckstrin homology domain containing proteins, leading to downstream signalling events crucial for proliferation, survival and migration. Class I PI3K enzymes consist of four distinct catalytic isoforms, PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ.There are three major classes of PI3K enzymes, being class IA widely associated to cancer. Class IA PI3K are heterodimeric lipid kinases composed of a catalytic subunit (p110α, p110β, or p110δ; encoded by PIK3CA, PIK3CB, and PIK3CD genes, respectively) and a regulatory subunit (p85).The PI3K pathway plays an important role in many biological processes, including cell cycle progression, cell growth, survival, actin rearrangement and migration, and intracellular vesicular transport.
||GDC-0032 is a potent β-sparing small molecule inhibitor of PI3K, with Ki values of 0.29 nM, 0.91 nM, 0.97 nM for PI3Kα, PI3Kβ and PI3Kγ, respectively.
||3-Methyladenine is a potent inhibitor of autophagy and PI3K, blocking autophagy through its effect on PI3K, with IC50s of 25 μM and 60 μM for Vps34 and PI3Kγ, respectively.
||LY294002 is a broad-spectrum inhibitor of PI3K, with IC50 of 0.5/0.57/0.97 μM for PI3Kα/PI3Kδ/PI3Kβ, respectively, also potently inhibits CK2 with IC50 of 98 nM.
||GDC-0941 is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).
||NVP-BKM120 is a pan-class I PI3K inhibitor, with IC50 of 52 nM/166 nM/116 nM/262 nM for p110α/p110β/p110δ/p110γ, respectively.
||BYL-719 is a potent and selective PI3Kα inhibitor with IC50 of 5 nM.
||GSK2126458 is a highly selective and potent inhibitor of PI3K with Ki of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM for p110α/β/δ/γ, mTORC1/2, respectively.
||Duvelisib is a selectivite p100δ inhibitor with IC50 of 2.5 nM, 27.4 nM, 85 nM and 1602 nM for p110δ, P110γ, p110β and p110α, respectively.
||PF-04691502 is a potent and selective inhibitor of PI3K and mTOR kinases with antitumor activity. PF-04691502 inhibits human and mouse PI3Kα with Ki of 1.8 and 1.2 nM, respectively, human PI3K isoforms β, δ, and γ with Ki of 2.1, 1.6, and 1.9 nM, respectively, and human mTOR with Ki of 16 nM.
||GSK2636771 is a potent, selective and orally bioavailable PI3Kβ inhibitor, sensitive to PTEN null cell lines.
||TG100-115 is a selective PI3Kγ/PI3Kδ inhibitor with IC50s of 83 and 235 nM, respectively.
||NVP-BGT226 is a potent pan-class I PI3K and mTOR catalytic inhibitor with IC50s of 4 nM, 63 nM and 38 nM for PI3Kα, PI3Kβ and PI3Kγ.
||PI3K inhibitor X
||PI3K inhibitor X is a representative and selective PI3Kα inhibitor extracted from patent WO2012006552A1, Compound 147 in Table 1.
||VS-5584 is a pan-PI3K/mTOR kinase inhibitor with IC50s of 2.6 nM, 3.3 nM, 21 nM, 2.7 nM, 3 nM and 3.4 nM for PI3Kα, PI3Kα mt H1047R, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively.
||PI3K-IN-1 is a potent inhibitor of PI3K, more information can be found in patent WO2012103524 A2 and WO2013147649 A2.
||XL147 is a potent and highly selective class I PI3Ks inhibitor with IC50s of 39 nM, 383 nM, 23 nM and 36 nM for PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ.
||AS-252424 is a potent and selective PI3Kγ inhibitor with an IC50 of 30±10 nM.
||PIK-90 is a DNA-PK and PI3K inhibitor, which inhibits p110α, p110γ and DNA-PK with IC50s of 11, 18 and 13 nM, respectively.
||PIK-294 is a potent p110δ-selective inhibitor with an IC50 of 10 nM.
||PQR309 is a potent, brain-penetrant, orally bioavailable, pan-class I PI3K/mTOR inhibitor with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively.
||CZC24832 is the first selective PI3Kγ inhibitor with IC50 of 27 nM, with 10-fold selectivity over PI3Kβ and >100-fold selectivity over PI3Kα and PI3Kδ.
||Vps34-PIK-III is a potent and selective inhibitor of VPS34 with an IC50 of 18 nM.
||SAR245409 is a potent PI3K inhibitor, which has a similar activity toward class I PI3K (IC50s=39, 113, 9 and 43 nM for p110α, p110β, p110γ and p110δ, respectively), also inhibits DNA-PK (IC50=150 nM) and mTOR (IC50=157 nM).
||BEZ235 is a dual pan-class I PI3K and mTOR kinase inhibitor with IC50 of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively.
||BAY 80-6946 is an ATP-competitive selective class-I PI3 kinases inhibitor, with IC50s of 0.5, 0.7, 3.7 and 6.4 nM for
PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, and much less active against mTOR (IC50=45 nM) and other PIKs (no inhibition at 1 μM).
||PKI-587 is a highly potent dual inhibitor of PI3Kα, PI3Kγ, and mTOR with IC50s of 0.4 nM, 5.4 nM and 1.6 nM, respectively.
||PI-103 is a potent PI3K/Akt and mTOR inhibitor with IC50 values of 2 nM for recombinant PI3K isoform p110α and 30 nM for mTOR
||GDC-0980 is a potent, class I PI3K inhibitor for PI3Kα/β/δ/γ with IC50 of 5 nM/27 nM/7 nM/14 nM in cell-free assays, respectively, and also a mTOR inhibitor with Ki of 17 nM in a cell-free assay, and highly selective versus other PIKK family kinases.
||TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit, used for cancer treatment.
||ZSTK474 is an ATP-competitive pan-class I PI3K inhibitor with IC50s of16 nM, 44 nM, 4.6 nM and 49 nM for PΙ3Κα, PI3Kβ, PI3Kδ and PI3Kγ, respectively.
||Quercetin, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC50 of 2.4±0.6 μM, 3.0±0.0 μM and 5.4±0.3 μM for PI3K γ, PI3K δ and PI3K β, respectively.
||AS-605240 is a specific and orally active inhibitor of the PI3Kγ, with an IC50 of 8 nM, and a Ki of 7.8 nM.
||HS-173 is a novel PI3K inhibitor, that is used for cancer treatment.
||AZD8186 is a PI3K inhibitor, which potently inhibits PI3Kβ (IC50=4 nM) and PI3Kδ (IC5050=12 nM) with selectivity over PI3Kα (IC50=35 nM) and PI3Kγ (IC50=675 nM).
||AZD 6482 is a potent and selective p110β inhibitor with IC50 of 0.69 nM.
||LY3023414 potently and selectively inhibits class I PI3K isoforms, mTORC1/2, and DNA-PK with IC50s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 165 nM and 4.24 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, mTOR and DNA-PK, respectively.
||GSK1059615 is a dual inhibitor of PI3Kα/β/δ/γ (reversible) and mTOR with IC50 of 0.4 nM/0.6 nM/2 nM/5 nM and 12 nM, respectively.
||Vps34-IN-1 is an inhibitor of Vps34 extracted from patent WO/2012085815 A1, compound example 16a; has an IC50 of 4 nM.
||AZD8835 is a potent and selective inhibitor of PI3Kα and PI3Kδ with IC50s of 6.2 and 5.7 nM, respectively.
||PF-4989216 is a potent and selective PI3Kα inhibitor with a Ki of 0.6 nM.
||CAY10505 is a potent and selective PI3Kγ inhibitor with an IC50 of 30 nM in neurons.
||AMG319 is a potent and selective PI3Kδ kinase inhibitor with IC50 of 18 nM.
||PI3Kγ inhibitor 1
||PI3Kγ inhibitor 1 is a PI3Kδ and PI3Kγ inhibitor extracted from patent WO2014004470A1, Compound 168 in Table 4, has IC50s of <100 nM.
||SF2523 is a highly selective and potent inhibitor of PI3K with IC50s of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.
||PF-04979064 is a potent and selective PI3K/mTOR dual kinase inhibitor with Kis of 0.13 nM and 1.42 nM for PI3Kα and mTOR, respectively.
||PI3Kα inhibitor 1
||PI3Kα inhibitor 1 is a selective PI3Kα inhibitor extracted from patent US/20120088764A1, Compound 243, has an IC50<0.1 μM, PI3Kα inhibitor 1 also inhibits HDAC (0.1 μM≤IC50≤1 μM) .
||740 Y-P (PDGFR 740Y-P) is a potent and cell permeable PI3K activator.
||GSK2269557 free base
||GSK2269557 free base is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9.
||MLN1117 is a selective p110α inhibitor with an IC50 of 15 nM.
||GDC-0326 is a potent and selective PI3Kα inhibitor with a Ki of 0.2 nM.
||NVP-BKM120 Hydrochloride is a pan-class I PI3K inhibitor, with IC50 of 52 nM/166 nM/116 nM/262 nM for p110α/p110β/p110δ/p110γ, respectively.
||PI3kδ inhibitor 1
||PI3kδ inhibitor 1 is a potent and selective PI3Kδ inhibitor with an IC50 of 3.8 nM.
||ON 146040 is a potent PI3Kα and PI3Kδ (IC50≈14 and 20 nM, respectively) inhibitor. ON 146040 also inhibits Abl1 (IC50<150 nM).
||CAL-130 is a PI3Kδ and PI3Kγ inhibitor with IC50s of 1.3 and 6.1 nM, respectively.
||CAL-130 is a PI3Kδ and PI3Kγ inhibitor with IC50s of 1.3 and 6.1 nM, respectively.
||SAR405 is a PIK3C3/Vps34 inhibitor with an IC50 of 1.2 nM. SAR405 also is a proximal inhibitor of the autophagy machinery.
||TGR-1202 is a novel PI3Kδ inhibitor, with IC50 and EC50 of 22.2 nM and 24.3 nM, respectively; Also active against CK1ε, with an EC50 value of 6.0 μM.
||Umbralisib (TGR-1202) R-enantiomer
||TGR-1202 R-enantiomer is a PI3Kδ inhibitor, which is the less active enantiomer of TGR-1202.
||Tenalisib (RP6530) is a novel, potent, and selective PI3Kδ and PI3Kγ inhibitor with IC50 values of 25 and 33 nM, respectively.
||NSC781406 is a highly potent PI3K and mTOR inhibitor with an IC50 of 2 nM for PI3Kα.
||IPI549 is a potent and selective PI3Kγ Inhibitor with an IC50 of 16 nM.
||PI3Kδ-IN-2 is a potent and selective inhibitor of PI3Kδ extracted from patent WO 2015055071 A1, compound 10; has an IC50 of 6.4 nM.
||GDC-0077 is an orally available PI3K inhibitor with potential antineoplastic activity. GDC-0077 is extracted from patent WO 2017001645 A1, formula I.
||PI-103 hydrochloride is a potent PI3K/Akt and mTOR inhibitor with IC50 values of 2 nM for recombinant PI3K isoform p110α and 30 nM for mTOR.
||CAL-130 Racemate is the racemate of CAL-130. CAL-130 Racemate is a PI3Kδ inhibitor.
||NVP-BAG956 is an ATP-competitive PI3K inhibitor with IC50s of 34, 56, 112 and 444 nM for PI3Kδ, PI3Kα, PI3Kγ and PI3Kβ, respectively.
||Pictilisib (GDC-0941) dimethanesulfonate
||GDC-0941 dimethanesulfonate is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).
||MDK34597 (PI3K inhibitor)
||MDK34597 is a PI3K inhibitor.MDK34597 is an analog of PI-103 and acts as a dual PI3K/mTOR Inhibitor.
||VPS34 inhibitor 1
||VPS34 inhibitor 1 (Compound 19, PIK-III analogue) is a potent and selective inhibitor of VPS34 with an IC50 of 15 nM.
||PQR530 is a selective, orally bioavailable, potent dual PI3K/mTORC1/2 inhibitor.
||A potent, selective, orally active p110δ/γ PI3K dual inhibitor with cellular IC50 of 0.29 and 7.1 nM, respectively.
||SF-1126 is a pan PI3K/BRD4 inhibitor, RGDS-conjugated LY294002 prodrug that exhibits increased solubility and binds to specific integrins.
||ST-168 is a novel potent, orally available MEK/PI3K bifunctional inhibitor with IC50 of 182, 69.2, 1482, 2293, and 41.7 nM for MEK1, PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ, respectively.
||AS2541019 is a novel potent, selective, orally active PI3Kδ inhibitor with IC50 of 20.1 nM, >100-fold selectivity over other PI3K isoforms.
||PI3Kδ inhibitor 52
||A potent, selective, and efficacious PI3Kδ inhibitor with IC50 of 1.7 nM, >100-fold selectivitity over PI3Kγ/α/β.
||PI3Kβ and δ inhibitor 20a
||A potent, highly selective PI3Kβ/δ inhibitor with IC50 of 7.8/5.3 nM respectively, with liitle to no activity on PI3Kα/γ (IC50=850/>10,000 nM).
||Seletalisib (UCB-5857) is a potent, ATP-competitive, and selective PI3Kδ inhibitor with IC50 of 12 nM.
||A novel potent and selective PI3Kδ inhibitor with biochemical IC50 of 11 nM.
||GSK-2269557 is a highly potent and selective inhibitor of PI3Kδ (pKi=10.1).
||SN-32976 is a novel, potent and selective class I PI3K and mTOR inhibitor with IC50 of 15.1/461/110/134/194 nM for PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ/mTOR, respectively.
||GNE-490 is a potent, selective, orally available class I PI3K inhibitor with IC50 of 3.5/25/5.2/15 nM for PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ.
||ST-162 is a potent, bifunctional MAPK/PI3K antagonist with IC50 of 191 nM and 398 nM for PI3Kα and MEK1, respectively.
||A novel specific p110β inhibitor with IC50 of 5.74 nM
||A potent, selective, orally bioavailable PI3Kδ inhibitor with IC50 of 2.6 nM
||A novel potent, selective, orally available PI3Kδ inhibitor with IC50 of 31 nM.