3-Methyladenine (3-MA)

Selective PI3K Inhibitors

CAL-101 (Idelalisib, GS-1101) : p110δ-selective, IC50=2.5 nM.

TGX-221 : p110β-specific, IC50=5 nM.

Most Potent PI3K Inhibitor

BEZ235 (NVP-BEZ235, Dactolisib) : p110α/γ/δ/β, IC50=4 nM/5 nM/7 nM/75 nM.

FDA-approved PI3K Inhibitor

CAL-101 (Idelalisib, GS-1101) : Approved by FDA for Relapsed Chronic Lymphocytic Leukemia, Follicular Lymphoma and Small Lymphocytic Lymphoma.

Newest PI3K Inhibitor

VS-5584 (SB2343) ^New : Potent and selective dual PI3K/mTOR inhibitor for mTOR, PI3Kα/β/δ/γ with IC50 of 3.4 nM and 2.6-21 nM, respectively.

Taselisib (GDC 0032) ^New

Taselisib (GDC 0032) is a potent, next-generation β isoform-sparing PI3K inhibitor targeting PI3Kα/δ/γ with K_i of 0.29 nM/0.12 nM/0.97nM, >10 fold selective over PI3Kβ.

Features:A beta isoform-sparing PI3K inhibitor.

Pilaralisib (XL147) ^New

Pilaralisib (XL147) 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. Phase 1/2.

GNE-317 ^New

GNE-317 is a potent, brain-penetrant PI3K inhibitor.

LY294002

LY294002 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.

Idelalisib (CAL-101, GS-1101)

Idelalisib (CAL-101, GS-1101) 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.

Wortmannin

Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Also blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays.

Dactolisib (BEZ235, NVP-BEZ235)

Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3^TopBP1-ER cell.

Buparlisib (BKM120, NVP-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. Phase 2.

Pictilisib (GDC-0941)

Pictilisib (GDC-0941) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Phase 2.

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. Phase 2.