PI3Kγ 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.

Quercetin, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC₅₀ of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively.

Alpelisib (BYL-719) is an orally active PI3Kα-selective inhibitor that blocks the conversion of PIP2 to PIP3, thereby inhibiting pathways including PI3K/AKT/mTOR, MAPK/ERK, Notch and JAK-STAT. Alpelisib also induces apoptosis, G0/G1 phase arrest and senescence; it significantly inhibits the proliferation, self-renewal, stemness and epithelial-mesenchymal transition (EMT) of tumor cells, reduces cancer stem cell populations and decreases the expression of stem cell markers. Alpelisib not only enhances the sensitivity to Eribulin (HY-13442) and exerts a synergistic effect with Paclitaxel (HY-B0015), but may also induce drug resistance by upregulating the SGK3/GSK3β/β-catenin signaling pathway. Alpelisib can be applied to research related to breast cancer, gastric cancer and lipomas associated with PTEN hamartoma tumor syndrome.

AZD-7648 is a potent, orally active, selective DNA-PK inhibitor with an IC₅₀ of 0.6 nM. AZD-7648 induces apoptosis and shows antitumor activity.

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

PIK-124 is a thiazolidinone-based PI3Kγ-biased PI3K inhibitor, with an IC₅₀ of 3 nM against PI3Kγ. PIK-124 exhibits cross-reactivity with PI3Kα (IC₅₀ = 23 nM), PI3Kδ (IC₅₀ = 340 nM), PI3KC2α (IC₅₀ = 140 nM) and PI3KC2β (IC₅₀ = 370 nM). PIK-124 is applicable to breast cancer-related research.

AM-8508 is an orally bioactive PI3Kδ inhibitor with an IC₅₀ of 0.016 μM. AM-8508 selectively inhibits PI3Kδ, thereby blocking AKT phosphorylation mediated by the B cell receptor. AM-8508 suppresses the formation of antigen-specific IgG and IgM in rats immunized with keyhole limpet hemocyanin. AM-8508 can be used for the research of inflammatory diseases.

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.

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.

Dactolisib (BEZ235) is an orally active and dual pan-class I PI3K and mTOR kinase inhibitor with IC₅₀s of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively. Dactolisib (BEZ235) inhibits both mTORC1 and mTORC2.

Gedatolisib (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. Gedatolisib is equally effective in both complexes of mTOR, mTORC1 and mTORC2.

Copanlisib (BAY 80-6946) is a potent, selective and ATP-competitive pan-class I PI3K inhibitor, with IC₅₀s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. Copanlisib has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. Copanlisib has superior antitumor activity.

Duvelisib (IPI-145) 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.

Eganelisib (IPI549) is a potent and selective PI3Kγ inhibitor with an IC₅₀ of 16 nM. Eganelisib shows >100-fold selectivity over other lipid and protein kinases.

Omipalisib (GSK2126458) is an orally active and highly selective inhibitor of PI3K with K_is 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. Omipalisib has anti-cancer activity.

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.

hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC₅₀ of 0.11 nM. hSMG-1 inhibitor 11j exhibits >455-fold selectivity for hSMG-1 over mTOR (IC₅₀=50 nM), PI3Kα/γ (IC₅₀=92/60 nM) and CDK1/CDK2 (IC₅₀=32/7.1 μM). hSMG-1 inhibitor 11j can be used for the research of cancer.

Paxalisib (GDC-0084) is a brain penetrant inhibitor of PI3K and mTOR, with K_is of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively.

Fimepinostat (CUDC-907) potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes with an IC₅₀ of 19/54/39 nM and 1.7/5.0/1.8/2.8 nM for PI3Kα/PI3Kβ/PI3Kδ and HDAC1/HDAC2/HDAC3/HDAC10 , respectively.

Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) is a potent, selective and ATP-competitive pan-class I PI3K inhibitor, with IC₅₀s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. Copanlisib dihydrochloride has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. Copanlisib dihydrochloride has superior antitumor activity.