PI3K

Rafutrombopag (tautomerism) (Hetrombopag) is an orally active nonpeptide thrombopoietin receptor (TPOR/MPL) agonist. Rafutrombopag can chelate iron and alleviate iron overload while promoting haematopoiesis. Rafutrombopag specifically stimulates proliferation and differentiation of human TPOR‐expressing cells, including 32D‐ MPL and human hematopoietic stem cells through stimulation of STAT, PI3K and ERK signalling pathways. Rafutrombopag effectively up-regulates G1-phase-related proteins, including p-RB, Cyclin D1 and CDK4/6, normalizes progression of the cell cycle, and prevents apoptosis by modulating BCL-XL/BAK expression in 32D-MPL cells. Rafutrombopag protects cardiomyocyte survival from oxidative stress damage as an enhancer of stem cells. Rafutrombopag can be used for the study of immune thrombocytopenia and oxidative stress-related cardiovascular disease.

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.

Ginsenoside F2 is an orally active bioactive compound that participates in the regulation of metabolism and inflammation. Ginsenoside F2 promotes the phosphorylation of AMPK and ACC, binds to PPARγ, inhibits the phosphorylation of MAPK, activates the PI3K/AKT/GSK-3β pathway, reduces GLRX expression, and regulates lipid metabolism. Ginsenoside F2 reduces ROS production and MDA levels, restores SOD activity in cells, and alleviates oxidative stress. Ginsenoside F2 induces cell apoptosis (Apoptosis) and increases the number of cleaved caspase-3-positive cells. Ginsenoside F2 reduces body weight gain, adipose tissue weight and serum lipid levels in obese mice, and activates the hepatic AMPK signaling pathway and the expression of antioxidant enzymes. Ginsenoside F2 alleviates atopic dermatitis in mice by inhibiting inflammation and reshaping the gut microbiota. Ginsenoside F2 is applicable to research related to insulin resistance, obesity, atopic dermatitis, liver cancer, glioblastoma and glioma.

1,3-Dicaffeoylquinic acid is a caffeoylquinic acid derivative that exhibits antioxidant activity and radical scavenging activity.

Ponicidin (Rubescensine B) is an orally active RIPK1 inhibitor with a K_d value of 135 nM. Ponicidin inhibits the JAK2/STAT3 pathway to induce apoptosis, activates the PI3K/Akt pathway, upregulates SIRT1 expression, alleviates oxidative stress, suppresses inflammatory responses and necroptosis, and blocks cell cycle progression. Ponicidin induces ROS production to exert antiproliferative and antiviral effects, while also improving cognitive function and reducing Aβ plaque deposition. Ponicidin can be used in studies related to hepatocellular carcinoma, Alzheimer's disease, and gastric cancer.

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.

Pinoresinol Diglucoside is an orally active lignan with multifunctional bioactivity. Pinoresinol Diglucoside interacts with targets including ALB, HIF1A, GSK3B, BCL2, MARK3, IL6, NF-κB p65, Nrf2, HO-1, and TLR4, and modulates pathways including PI3K-Akt, estrogen, MAPK, Rap1, AKT/mTOR/NF-κB, and TGF-β1/Smads. Pinoresinol Diglucoside regulates osteogenesis, bone resorption, oxidative stress, inflammation, apoptosis, ferroptosis, ferritinophagy, cardiac fibrosis, and vasorelaxation. Pinoresinol Diglucoside can be used for the research of osteoporosis, ischemia/reperfusion-induced brain injury, Alzheimer’s disease, myocardial ischemia-reperfusion injury, chondrodysplasia, diabetic cardiomyopathy, cardiac hypertrophy, hypertension, cisplatin-induced hearing loss, atherosclerotic cardiovascular diseases, and disuse osteoporosis.

Heterophyllin B is an active cyclic peptide isolated from Pseudostellaria heterophylla. Heterophyllin B provides a novel strategy for the treatment of esophageal cancer.

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.

Vasculotide is a blood-brain barrier (BBB)-penetrant Tie2 agonist. Vasculotide binds to a unique domain of Tie2, induces receptor clustering to drive phosphorylation, activates downstream PI3K/Akt and eNOS pathways, enhances inter-endothelial cell junctions (such as VE-cadherin and claudin-5), and inhibits inflammatory adhesion molecules, ultimately stabilizing the vascular endothelial barrier and reducing its permeability. Vasculotide alleviates pulmonary microvascular leakage and microcirculatory dysfunction caused by cardiopulmonary bypass, acts as an adjuvant radioprotective agent to reduce acute radiation dermatitis, and promotes BBB recovery after focused ultrasound (FUS). Combination of Vasculotide with antibiotics reduces lung injury.

Hederacolchiside A1, isolated from Pulsatilla chinensis, suppresses proliferation of tumor cells by inducing apoptosis through modulating PI3K/Akt/mTOR signaling pathway. Hederacolchiside A1 has antischistosomal activity, affecting parasite viability both in vivo and in vitro.

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.

EGCG Octaacetate (AcEGCG) is a proagent of Green tea epigallocatechin-3-gallate (EGCG). EGCG Octaacetate decreases the proinflammatory mediator levels by down-regulating of PI3K/Akt/NFκB phosphorylation and p65 acetylation. EGCG octaacetate is the potential antibacterial compound for gram-positive bacteria (GPB) and gram-negative bacteria (GNB). EGCG Octaacetate exhibits antioxidant, anti-angiogenesis, anti-inflammatory and antitumor activities.

Telocinobufagin (Telobufotoxin; Telocinobufogenin) is an orally active bufadienolide with potential anti-tumor effects. Telocinobufagin exerts its anti-cancer effects on non-small cell carcinoma, osteosarcoma, thyroid cancer, breast cancer and head and neck squamous cell carcinoma by inhibiting the STAT3, JAK2/STAT3, LARP1-mTOR, PI3K/Akt/Snail and PLK1 pathways, and can also induce tumor cell apoptosis. Telocinobufagin enhances the Th1 immune response and protects against Salmonella typhimurium infection. Telocinobufagin has a strong cardiac-stimulating effect by inhibiting the activity of Na⁺/K⁺-ATPase, and it can promote renal fibrosis. Telocinobufagin demonstrates non-opioid analgesic effects in various acute pain models.

Typhaneoside is an orally active activator of PI3K/Akt/mTOR and farnesoid X receptor. Typhaneoside promotes the activation of AMPK and Caspase-3, induces apoptosis, ferroptosis, autophagy, ROS accumulation, cell cycle arrest at the G₂/M phase, and reduces cancer cell viability. Typhaneoside improves glucose and lipid metabolism, alleviates inflammatory responses, oxidative stress and hepatic lipid accumulation, and exerts hepatoprotective effects. Typhaneoside can be used in research related to heart failure after myocardial infarction, acute myeloid leukemia, non-alcoholic fatty liver disease and neurological disorders.

Isorhamnetin-3-O-glucoside is an orally active natural compound. Isorhamnetin 3-O-glucoside increases P-ERK, ERK, P-Akt (Ser473), P-PI3K, and PDX-1. Isorhamnetin 3-O-glucoside downregulates C/EBPα and inhibits lipase. Isorhamnetin 3-O-glucoside reduces lipids and inhibits obesity.

20-5,14-HEDE (WIT003) is an analog of 20-HETE. 20-5,14-HEDE activates PI3K/Akt signaling pathway, thereby exhibiting anti-apoptotic and cell survival promoting effects. 20-5,14-HEDE is the agonist for 20-HETE that increases intracellular Ca²⁺ concentrations, thereby enhancing vasoconstriction.

Phellopterin, an orally active furocoumarin with multiple biological activities. Phellopterin is a partial agonist of the central benzodiazepine receptors. Phellopterin exerts anti-inflammatory effects by upregulating SIRT1, downregulating ICAM-1 (reducing chronic inflammation, aiding diabetic ulcer healing), inhibiting STAT3 phosphorylation (easing atopic dermatitis inflammation), regulating Akt/PKC pathways (lowering TNF-α-induced VCAM-1 to block monocyte adhesion), and inhibiting TLR4/NF-κB pathway and macrophage M2 polarization (alleviating colitis-related cancers). Phellopterin suppresses ovarian cancer progression via inhibiting the PU.1/CLEC5A/PI3K-AKT loop (inducing cell cycle arrest, apoptosis, DNA damage). Phellopterin alleviates murine diabetes by promoting adipocyte differentiation and increasing PPARγ. Phellopterin also has anti-HSV-1 activity. Phellopterin can be used for studying anti-inflammation, anti-cancer (e.g., ovarian cancer, colitis cancer), blood glucose lowering, anti-diabetes, and anti-virus.