PI3K Inhibitor

Isorhamnetin is a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L.. Isorhamnetin suppresses skin cancer through direct inhibition of MEK1 and PI3K.

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.

STX-478 (compound 80) is an oral CNS-penetrant allosteric mutant-selective PI3Kα inhibitor. STX-478 shows robust and durable tumor regression and can be used in cancer research.

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.

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.

YM-201636 is a potent and selective PIKfyve inhibitor with an IC₅₀ of 33 nM. YM-201636 also inhibits p110α with an IC₅₀ of 3.3 μM. YM-201636 inhibits retroviral replication.

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.

D-GsMTx4 is a spider peptide and the D enantiomer of GsMTx4 (HY-P1410). D-GsMTx4 inhibits the mechanosensitive ion channel Piezo2. D-GsMTx4 inhibits [Ca²⁺]_i elevation. D-GsMTx4 inhibits mTOR and PI3K-Akt signaling pathways. D-GsMTx4 inhibits mechanical allodynia and thermal hyperalgesia. D-GsMTx4 can be used in researches of mechanical stress, chronic pain and idiopathic pulmonary fibrosis.

Onvoloxastat (ML355) is an orally active selective 12-LOX inhibitor with an IC₅₀ of 0.34 μM. Onvoloxastat inhibits platelet activation by blocking thrombin- or thromboxane A2-induced phosphorylation of Akt, PI3K and Erk1/2. At low doses (1-20 μM), it mainly acts by reducing ROS levels, while at high doses (50 μM), it functions via activating the cAMP pathway. Onvoloxastat can be used in research related to thrombosis and diabetes.

iMDK is a potent PI3K inhibitor and inhibits the growth factor MDK (also known as midkine or MK). iMDK suppresses non-small cell lung cancer (NSCLC) cooperatively with A MEK inhibitor without harming normal cells and mice.

Phlorizin (Floridzin) is an orally active non-selective sodium-glucose cotransporter (SGLT) inhibitor, with an IC₅₀ of 0.04 μM and a K_i of 39 nM against hSGLT2, and an IC₅₀ of 0.17 μM and a K_i of 0.31 μM against hSGLT1. Phlorizin promotes GLUT4 translocation, inhibits gluconeogenesis and promotes glycogen synthesis by activating the PI3K/Akt/mTOR pathway. Phlorizin reduces DNA damage and apoptosis (apoptosis) by inhibiting the NF-κB inflammatory pathway. Phlorizin induces apoptosis via activating the Caspase pathway by antagonizing the JAK/STAT3 and PCK pathways. Phlorizin also exhibits antibacterial, anti-inflammatory and neuroprotective activities.

LY294002 hydrochloride is a potent and broad-spectrum PI3K inhibitor, with IC₅₀ values of 0.5, 0.57, and 0.97 μM for P110α, P110δ and P110β, respectively. LY294002 hydrochloride also inhibits CK2 with an IC₅₀ of 98 nM. LY294002 hydrochloride can be used for pancreatic cancer research.

Zovegalisib (RLY-2608) is an orally active first-in-class allosteric mutant-selective inhibitor of PI3Ka with anti-tumor activity. Zovegalisib inhibits tumor growth in PIK3CA-mutant xenograft mice models with minimal impact on insulin.

Liensinine is a bisbenzylisoquinoline alkaloid. By inhibiting the PI3K/AKT and JNK/p38-MAPK signaling pathways, Liensinine suppresses autophagy and apoptosis, clears Aβ, and exerts anti-inflammatory, antioxidant and neuroprotective effects. Liensinine activates AMPK and inhibits the expression of HIF-1α and VEGF, thereby suppressing angiogenesis. Liensinine exerts anti-tumor effects through ROS-mediated inhibition of the JAK2/STAT3 signaling pathway. Liensinine can be used for the research of diseases such as Alzheimer's disease, hepatocellular carcinoma, osteosarcoma, sepsis-induced organ injury and stroke.

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.

Ononin is an orally active isoflavone. Ononin inhibits the ERK/JNK/p38 and PI3K/Akt/mTOR pathways. Ononin regulates Apoptosis. Ononin has anti-tumor effects on laryngeal cancer and lung cancer. Ononin has neuroprotective effects. Ononin alleviates endoplasmic reticulum stress and diabetic nephropathy.

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.

Isoacteoside is a natural product that can significantly inhibit the formation of glycation end products. Isoacteoside regulates the AKT/PI3K/m-TOR/NF-κB signaling pathway, induces apoptosis in OVCAR-3 cell. Isoacteoside exhibits antitumor, anti-inflammatory, anti-obesity and neuroprotective activities.