Vps34 Inhibitor

3-Methyladenine (3-MA) is a PI3K inhibitor. 3-Methyladenine is a widely used inhibitor of autophagy via its inhibitory effect on class III PI3K.

Idelalisib (CAL-101; GS-1101) is a highly selective and orally bioavailable p110δ inhibitor with an IC₅₀ of 2.5 nM, showing 40- to 300-fold selectivity for p110δ over other PI3K class I enzymes.

SAR405 is a first-in-class, selective, and ATP-competitive PI3K class III (PIK3C3) isoform Vps34 inhibitor (IC₅₀=1.2 nM; K_d=1.5 nM). SAR405 inhibits autophagy induced either by starvation or by mTOR inhibition. Anticancer activity.

Buparlisib (BKM120; NVP-BKM120) is a pan-class I PI3K inhibitor, with blood-brain barrier permeability. Buparlisib has IC₅₀s of 52, 166, 116 and 262 nM for p110α, p110β, p110δ and p110γ, respectively.

Vps34-IN-1 is a potent and selective inhibitor of class III Vps34 PI3K. Vps34-IN-1 inhibits phosphorylation of PtdIns by recombinant insect cell expressed Vps34-Vps15 complex with an IC₅₀ of ~25 nM. Vps34-IN-1 can suppress SGK3 activation by reducing PtdIns(3)P levels via lowering phosphorylation of T-loop and hydrophobic motifs. Vps34-IN-1 modulates autophagy.

PI-103 is a potent PI3K and mTOR inhibitor with IC₅₀s of 8 nM, 88 nM, 48 nM, 150 nM, 20 nM, and 83 nM for p110α, p110β, p110δ, p110γ, mTORC1, and mTORC2. PI-103 also inhibits DNA-PK with an IC50 of 2 nM. PI-103 induces autophagy.

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.

Autophinib is a potent, selective autophagy inhibitor with IC₅₀s of 90 nM and 40 nM for starvation- and Rapamycin-induced autophagy, respectively. Autophinib is also an ATP competitive Vacuolar Protein Sorting 34 (VPS34) inhibitor with an IC₅₀ of 19 nM. Autophinib inhibits autophagy induced by starvation or Rapamycin by targeting VPS34.

PIK-93 is the first potent, synthetic PI4K (PI4KIIIβ) inhibitor with IC₅₀ of 19 nM, and also inhibits PI3Kγ and PI3Kα with IC₅₀ of 16 nM and 39 nM, respectively.

Bimiralisib (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. Bimiralisib is an mTORC1 and mTORC2 inhibitor.

Vps34-PIK-III is an orally active and selective VPS34 inhibitor (IC₅₀=18 nM). Vps34-PIK-III effectively inhibits autophagy and can be used as a molecular tool. vps34-PIK-III is also a PI3K inhibitor that inhibits the expression of genes in liver cancer stem cells (CSCs).

VS-5584 is a pan-PI3K/mTOR kinase inhibitor with IC₅₀s of 16 nM, 68 nM, 42 nM, 25 nM, and 37 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively. VS-5584 simultaneously blocks mTORC2 as well as mTORC1.

Pilaralisib (XL147; SAR245408) 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.

AZD 6482 (KIN-193) is a potent and selective p110β inhibitor with an IC₅₀ of 0.69 nM.

PIK-75 hydrochloride is a reversible DNA-PK and p110α-selective inhibitor, which inhibits DNA-PK, p110α and p110γ with IC₅₀s of 2, 5.8 and 76 nM, respectively. PIK-75 hydrochloride inhibits p110α >200-fold more potently than p110β (IC₅₀=1.3 μM). PIK-75 hydrochloride induces apoptosis.

PIK-75 is a reversible DNA-PK and p110α-selective inhibitor, which inhibits DNA-PK, p110α and p110γ with IC₅₀s of 2, 5.8 and 76 nM, respectively. PIK-75 inhibits p110α >200-fold more potently than p110β (IC₅₀=1.3 μM). PIK-75 induces apoptosis.

SB02024 is a potent and orally active VPS34 inhibitor. SB02024 inhibits Vps34 kinase activity. SB02024 induces CCL5 and CXCL10 via STAT1/IRF7. SB02024 shows anticancer activity.

Buparlisib Hydrochloride (BKM120 Hydrochloride) is a CNS-penetrant pan-class I PI3K inhibitor, with IC₅₀ of 52 nM/166 nM/116 nM/262 nM for p110α/p110β/p110δ/p110γ, respectively.

SAR-260301 is an orally available and selective PI3Kβ inhibitor with an IC₅₀ of 23 nM.

Vps34-IN-2 is a novel, potent and selective inhibitor of Vps34 with IC₅₀s of 2 and 82 nM on the Vps34 enzymatic assay and the GFP-FYVE cellular assay, respectively. Vps34-IN-2 shows antiviral activity against SARS-CoV-2 (IC₅₀ of 3.1 μM), HCoV-229E (IC₅₀ of 0.7 μM) and HCoV-OC43.