PI3K Inhibitor

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.

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.

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.

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).

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.

Fusaric acid is an orally active multi-pathway inhibitor with the activity of inducing oxidative stress and apoptosis. Fusaric acid can chelate divalent metal cations, damage mitochondrial membrane structure, and activate apoptosis-related proteases such as Caspase-3/7, -8, and -9. Fusaric acid also regulates Bax/Bcl-2 protein, inhibits fibrosis-related signaling pathways such as NF-κB, TGF-β₁/SMADs, and PI3K/AKT/mTOR, and reduces collagen deposition. Fusaric acid is also a dopamine β-hydroxylase inhibitor, which reduces endogenous levels of norepinephrine and epinephrine in the brain, heart, spleen, and adrenal glands. Fusaric acid can play a role in myocardial fibrosis and improve cardiac hypertrophy in heart disease, and can also be used in the study of esophageal cancer and liver cancer.

Disitertide (P144) diammonium is a peptidic transforming growth factor-beta 1 (TGF-β1) inhibitor specifically designed to block the interaction with its receptor. Disitertide diammonium is also a PI3K inhibitor and an apoptosis inducer.

PI3K-IN-1 (XL-147 derivative 1) is a potent inhibitor of PI3K. PI3K-IN-1 (25 μM) blocks PI3K/Akt signaling pathways.

Methyl Eugenol is a bait that has oral activity against oriental fruit fly (Hendel).Methyl Eugenol has anti-cancer and anti-inflammatory activities. Methyl Eugenol can induce Autophagy in cells. Methyl Eugenol can be used in the study of intestinal ischemia/reperfusion injury.

SQLE-IN-1 (compound 19) is a squalene epoxidase (SQLE) inhibitor. SQLE-IN-1 inhibits the proliferation and migration of Huh7 cells. SQLE-IN-1 inhibits the cell cholesterol generation. SQLE-IN-1 increases the expression of PTEN and inhibits PI3K and AKT.

Raddeanin A is an oleanane-type triterpenoid saponin with oral activity. Raddeanin A inhibits SRC, mTOR, JNK, VEGFR2, NLRP3 inflammasome, Wnt/β-catenin, Wee1, PI3K/AKT signaling pathway, MAPK/ERK signaling pathway, AR-FL, AR-Vs, and downregulates the expression of p-PI3K and p-AKT. Raddeanin A inhibits osteoclast formation, bone resorption, osteolysis, cancer cell invasion, migration, proliferation, angiogenesis and epithelial-mesenchymal transition, while induces apoptosis, cell cycle arrest, ROS production, immunogenic cell death and dendritic cell maturation. Raddeanin A improves blood-retinal barrier function, alleviates inflammation, regulates the tumor microenvironment, and enhances the activity of anti-PD-1 antibody. Raddeanin A is applicable to the research of breast cancer-associated osteolysis, human osteosarcoma, colorectal cancer, glioblastoma, Alzheimer's disease, cholangiocarcinoma, melanoma, non-small cell lung cancer, castration-resistant prostate cancer and multiple myeloma.

Kukoamine B, a spermine alkaloid, is a potent dual LPS and CpG DNA inhibitor with K_d values of 1.23 µM and 0.66 µM, respectively. Kukoamine B exerts anti-inflammatory, anti-diabetic, anti-oxidant, anti-osteoporotic and neuroprotective effects. Kukoamine B has the potential for the study of sepsis.

PITCOIN4 is a highly selective Class II Alpha PI3K-C2α inhibitor. PITCOIN4 shows nanomolar inhibition of PI3K-C2α and >100-fold selectivity in a general kinase panel.

CAY10526 is an inhibitor of Y-box binding protein 1 (YB-1) and microsomal prostaglandin E2 synthase 1 (mPGES1). CAY10526 inhibits the production of PGE₂ by suppressing YB-1 and mPGES1. CAY10526 induces cell apoptosis (apoptosis) and inhibits the JAK/STAT, TGF-β/Smad3 and PI3K/AKT signaling pathways. CAY10526 can be used in research related to melanoma, prostate cancer, esophageal adenocarcinoma, T-cell lymphoma, etc.

Neoandrographolide is a diterpenoid compound isolated from Andrographis paniculata. Neoandrographolide inhibits osteoclasts differentiation and bone resorption through inhibition of MAPK/NF-κB/PI3K/AKT/GSK3β/PPAR/CAMK signaling pathway. Neoandrographolide inhibits apoptosis in rat embryonic ventricular cardiomyocytes. Neoandrographolide inhibits iNOS and the generation of ROS, activates eNOS, exhibiting anti-inflammatory and hypolipidemic activity.

GNE-317 is a PI3K/mTOR inhibitor, is able to cross the blood-brain barrier (BBB).

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

Naphthazarin (DHNQ) is a microtubule depolymerizing agent. Naphthazarin can improve motor function and reduce neuroinflammation in mouse models of Parkinson's disease. Naphthazarin can induce tumor cell apoptosis, autophagy, and cell cycle arrest. Naphthazarin can also induce erythrocyte apoptosis. Naphthazarin can be used in the research of tumors and neurodegenerative diseases.

Jujuboside B is a bioactive saponin component isolated from Ziziphi Spinosae Semen (sour jujube seed), with oral efficacy and blood-brain barrier permeability. Jujuboside B induces acute leukemia cell death and drives necroptosis apoptosis by activating the RIPK1/RIPK3/MLKL pathway. Jujuboside B upregulates the expression of NOXA, PARP and caspase-3, activates AMPK, inhibits the proliferation of breast cancer cells, and induces cell apoptosis and autophagy. Jujuboside B inhibits angiogenesis and tumor growth by blocking the VEGFR-2 signaling pathway. Jujuboside B alleviates liver injury in mice by regulating the Nrf2-STING signaling pathway. Jujuboside B alleviates liver injury by regulating anti-inflammatory responses and downregulating the expression of 11β-HSD2. Jujuboside B induces ferroptosis and overcomes radioresistance in non-small cell lung cancer via the PPARγ-ATF3-Gpx4 signaling pathway. Jujuboside B exerts inhibitory effects on platelet aggregation. Jujuboside B inhibits febrile seizures by suppressing the activity of AMPA receptors. Jujuboside B reverses chronic unpredictable mild stress-promoted tumor progression by blocking the PI3K/Akt and MAPK/ERK pathways and dephosphorylating CREB signaling. Jujuboside B is applicable to related studies on acute leukemia, breast cancer, PM_2.5-induced lung injury, hepatotoxicity, liver injury, colorectal cancer, non-small cell lung cancer, thromboembolic diseases, cardiovascular diseases associated with high platelet aggregation, febrile seizures, and depressive-like phenotypes.

Glaucocalyxin A, an ent-kauranoid diterpene from Rabdosia japonica var., induces apoptosis in osteosarcoma by inhibiting nuclear translocation of Five-zinc finger Glis 1 (GLI1) via regulating PI3K/Akt signaling pathway. Glaucocalyxin A has antitumor effect.