PI3K Inhibitor

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.

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

GO-203 TFA is a potent MUC1-C oncoprotein inhibitor. GO-203 TFA is an all D-amino acid peptide that consists of a poly-R transduction domain linked to a CQCRRKN motif that binds to the MUC1-C cytoplasmic tail and blocks MUC1-C homodimerization. GO-203 TFA downregulates TIGAR (TP53-induced glycolysis and apoptosis regulator) protein synthesis by inhibiting the PI3K-AKT-S6K1 pathway. GO-203 TFA induces the production of ROS and loss of mitochondrial transmembrane potential. GO-203 TFA inhibits the growth of colon cancer cells in vitro and as xenografts in nude mice.

hSMG-1 inhibitor 11e is a potent and selective hSMG-1 kinase inhibitor with an IC₅₀ of <0.05 nM. hSMG-1 inhibitor 11e shows >900-fold selectivity over mTOR (IC₅₀ of 45 nM), PI3Kα/γ (IC₅₀s of 61 nM and 92 nM) and CDK1/CDK2 (IC₅₀s of 32 μM and 7.1 μM).

Samotolisib (LY3023414) potently and selectively inhibits class I PI3K isoforms, DNA-PK, and mTORC1/2 with IC₅₀s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, DNA-PK and mTOR, respectively. Samotolisib potently inhibits mTORC1/2 at low nanomolar concentrations.

Sophocarpine is a PTEN activator and an inhibitor of PI3K/Akt, MEK/ERK, and NF-κB signaling pathways. Sophocarpine upregulates PTEN expression and inhibits PI3K/Akt phosphorylation, arrests tumor cell cycle and induces apoptosis. Sophocarpine inhibits MEK/ERK phosphorylation and VEGF secretion, reducing tumor cell migration. Sophocarpine can also inhibit NF-κB activation and p38 and JNK phosphorylation, reduce the expression of inflammatory factors such as iNOS and COX-2, and activate the Nrf2/HO-1 pathway to reduce oxidative stress. Sophocarpine has anti-tumor, anti-inflammatory, antioxidant and anti-apoptotic effects, and can be used in the research of cancers such as glioblastoma and colorectal cancer, inflammation-related diseases, and Doxorubicin (HY-15142A)-induced cardiac damage.

Apitolisib (GDC-0980; GNE 390; RG 7422) is a selective, potent, orally bioavailable Class I PI3 kinase and mTOR kinase (TORC1/2) inhibitor with IC₅₀s of 5 nM/27 nM/7 nM/14 nM for PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ, and with a?K_i?of 17 nM for mTOR.

Resibufogenin is an orally active anticancer agent. Resibufogenin can be extracted from toad venom. Resibufogenin blocks signaling pathways such as PI3K/Akt, NF-κB, AP-1, activates GSK-3β, and regulates cyclin D1. Resibufogenin can activate central neurons. Resibufogenin has anti-inflammatory activity. Resibufogenin has anti-tumor effects on a variety of tumors such as multiple myeloma, renal cancer, colorectal cancer, pancreatic cancer, and glioma.

10-Gingerol is an AMPK agonist, which is found in the ginger oleoresin from fresh rhizome with anti-inflammatory, antioxidant and anti-proliferative activities. 10-Gingerol suppresses neointimal hyperplasia and inhibits vascular smooth muscle cell proliferation. 10-Gingerol exhibits substantial scavenging activities with an IC₅₀ value of 10.47 μM against DPPH radical, an IC₅₀ value of 1.68 μM against superoxide radical and an IC₅₀ value of 1.35 μM against hydroxyl radical. 10-Gingerol inhibits the proliferation of MDA-MB-231 tumor cell line with an IC₅₀ of 12.1 μM. 10-Gingerol suppresses the proliferation, migration, invasion, and induced apoptosis through targeting the PI3K/Akt signaling pathway in MDA-MB-231/IR cells. 10-Gingerol can be used in research on various common cancers such as ovarian cancer and colon cancer, as well as colitis and neurodegenerative diseases.

Bimiralisib (PQR309) is an orally active, blood-brain barrier-penetrant PI3K/mTOR inhibitor with in vitro antiproliferative activity and in vivo antitumor activity. Bimiralisib induces G1 cell cycle arrest, apoptosis and cell death in cancer cells, while inhibiting cancer cell proliferation, migration, invasion, colony formation and spheroid generation. Bimiralisib upregulates the expression of E2F4. The combination of Bimiralisib with venetoclax enhances therapeutic efficacy in acute myeloid leukemia models. Bimiralisib can be used in cancer-related research.

Veratramine (NSC17821; NSC23880) is an orally active inhibitor of the PI3K/Akt/mTOR signaling pathway and a SIGMAR1 modulator. Veratramine induces autophagic apoptosis of tumor cells, arrests the cell cycle at the G0/G1 phase, and inhibits epithelial-mesenchymal transition (EMT)-related proteins to reduce tumor migration. Veratramine reduces spinal cord and sciatic nerve pathological damage in a neuropathy model by inhibiting SIGMAR1 binding to NMDAR and phosphorylation of NMDAR Ser896. Veratramine has anti-tumor proliferation, apoptosis induction, anti-inflammatory and neuroprotective activities, and can be used in the study of cancers such as liver cancer and osteosarcoma, as well as diabetic peripheral neuropathy.

Umbralisib (TGR-1202) is an orally active, potent and selective dual PI3Kδ and casein kinase-1-ε (CK1ε) inhibitor, with EC₅₀ of 22.2 nM and 6.0 μM, respectively. Umbralisib exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib can be used for haematological malignancies reseach.

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).

ZSTK474 is an ATP-competitive pan-class I PI3K inhibitor with IC₅₀s of 16 nM, 44 nM, 4.6 nM and 49 nM for PΙ3Κα, PI3Kβ, PI3Kδ and PI3Kγ, respectively.

Deoxyshikonin increases the expression of VEGF-C and VEGF-A mRNA in HMVEC-dLy, promotes HIF-1α and HIF-1β subunit interaction and binds to specific DNA sequences targeted by HIF. Deoxyshikonin inhibited colorectal cancer (CRC) through the PI3K/Akt/mTOR pathway. Deoxyshikonin has proangiogenesis effect and antitumor activity. Deoxyshikonin is an antibacterial agent against methicillin-resistant S. aureus (MRSA) and S. pneumonia (MIC=17 μg/mL).

BGT226 (NVP-BGT226) is a PI3K (with IC₅₀s of 4 nM, 63 nM and 38 nM for PI3Kα, PI3Kβ and PI3Kγ)/mTOR dual inhibitor which displays potent growth-inhibitory activity against human head and neck cancer cells.

CGS 15943 is an orally bioavailable non-xanthine Adenosine Receptor antagonist. Its K_i for human A1, A2A, A2B, and A3 Adenosine Receptors are 3.5, 4.2, 16, and 50 nM in transfected CHO cells, respectively. .

Beauvericin is a cyclohexapeptide Fusarium toxin with insecticidal, antibacterial, anticancer, antiviral and cytotoxic activities. Beauvericin causes cellular genotoxicity by producing DNA breaks, chromosomal aberrations and micronuclei, and inhibits the PI3K/AKT pathway to induce apoptosis, thereby inhibiting the growth of HCC. In addition, Beauvericin affects immune function by inhibiting lymphocyte proliferation and interfering with the differentiation process of human monocytes into macrophages.

Micheliolide is a sesquiterpene lactone with anti-cancer and anti-inflammatory effects, which is derived from Michelia compressa and Michelia champaca. Micheliolide can attenuate high glucose-stimulated NF-κB activation, IκBα degradation, and the expression of MCP-1, TGF-β1, and FN in mouse mesangial cells. Micheliolide inhibits LPS (HY-D1056)-induced activation of NF-κB and PI3K/Akt/p70S6K pathways to play an anti-inflammatory role. Micheliolide inhibits dextran sodium sulphate (DSS) (HY-116282)-induced inflammatory intestinal disease, colitis-associated cancer and rheumatic arthritis.

Quercetin dihydrate, a natural flavonoid, is a stimulator of recombinant SIRT1 and a PI3K inhibitor with IC₅₀s of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively.