akt-in-2

AKT-IN-2 is a selective, and orally bioavailable AKT inhibitor (IC50: 5 nM for AKT1).

VEGFR-2 AKT-IN-2 (Compound 5) is an inhibitor of VEGFR-2 AKT, with an IC50 of 0.061 μM for VEGFR in human liver cancer cells. It reduces total and phosphorylated AKT in cells, increases BAX and caspase-3 levels, and decreases Bcl-2, thereby inducing apoptosis. Additionally, VEGFR-2 AKT-IN-2 halts the cell cycle at the S phase and inhibits the growth of human liver cancer cells.

PI3K AKT-IN-2, a dual inhibitor of PI3K and AKT, prevents the epithelial-mesenchymal transition (EMT) and promotes apoptosis. Additionally, it impedes tubulin polymerization.

PI3K Akt mTOR-IN-2 is a potent PI3K AKT mTOR inhibitor with anticancer effects and selectivity for MDA-MB-231 cells (IC50 2.29 μM). It induces cell cycle arrest and apoptosis in cancer cells.

AKT-IN-25 (Compound 14a) is an inhibitor of Akt that prevents the phosphorylation of Akt, thereby hindering the PI3K Akt mTOR signaling pathway. It arrests the cell cycle at the G1 phase, inhibits the migration of PANC-1 cells, and suppresses the proliferation of cancer cells PANC-1, PATU-T, and SUIT-2, with IC50 values of 3.05, 1.32, and 3.85 μM, respectively.

VEGFR-2 AKT-IN-1 (compound 17) is a dual inhibitor of VEGFR-2 and AKT with IC50 values of 0.164 μM and 0.452 μM, respectively. It exhibits antitumor activity.

AKT-IN-24 (Compound M17) is an allosteric inhibitor of AKT exhibiting antitumor activity. In combination with Trametinib, it targets the AKT mTOR and MEK ERK signaling pathways while inhibiting epithelial-mesenchymal transition, resulting in a synergistic suppression effect on TNBC. This combination promotes apoptosis and inhibits cell proliferation and migration.

AKT-IN-26 (Compound 453) is an AKT inhibitor that binds to the Pleckstrin Homology (PH) domain of AKT. It is useful for research related to cell proliferation and cancer involving the AKT pathway.

AKT-IN-22 (compound 0R4) serves as a potent allosteric inhibitor of AKT, exhibiting anticancer properties [1].

Polyphyllin D induces apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C, and cleaved-caspase-3 levels. Polyphyllin D has an anti-angiogenic effect. Polyphyllin D has toxicity in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis erythroptosis. Polyphyllin D has strong anticancer activity, can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

6'-GNTI dihydrochloride is a κ-opioid receptor (KOR) agonist that favors activation of G-protein-mediated signaling over recruitment of β-aspirin 2. 6'-GNTI dihydrochloride only activates the Akt pathway in striatal neurons.

ZINC00640089 is a selective lipid carrier protein-2 (LCN2) inhibitor. ZINC00640089 inhibited cell proliferation and cell viability, and reduced AKT phosphorylation in SUM149 cells. ZINC00640089 can be used to study inflammatory breast cancer (IBC).

Beta-Sitosterol (SKF 14463) has recently been shown to induce G2 M arrest, endoreduplication, and apoptosis through the Bcl-2 and PI3K Akt signaling pathways. Beta-Sitosterol (SKF 14463) , a main dietary phytosterol found in plants, may have the potential for prevention and therapy for human cancer. Although the exact mechanism of action of Beta-Sitosterol (SKF 14463) is unknown, it may be related to cholesterol metabolism or anti-inflammatory effects (via interference with prostaglandin metabolism). Beta-Sitosterol (SKF 14463) induces apoptosis and activates key caspases in MDA-MB-231 human breast cancer cells.

Ethyl gallate (gallic acid ethyl ester) obviously decreases cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner, exhibits cytotoxicity in a dose-dependent manner. Ethyl gallate can inhibit the abilities of invasion of breast cancer in vitro by inhibiting the mRNA levels of MMP-9 MMP-2, phosphorylation of Akt and protein expression of NF-κB and inhibits hydrogen peroxide signaling, may represent an alternative class of vasopressors for use in septic shock. Also, Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K Akt pathway, which may contribute to inhibiting their downstream targets such as NF-κB p-65, Bcl-2 Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells, could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy.

5,6-Benzoflavone (β-Naphthoflavone) is an exogenous ligand for the aryl hydrocarbon receptor, which disrupts zinc homeostasis in human hepatocellular carcinoma HepG2 cells. 5,6-Benzoflavone (β-Naphthoflavone) possesses anti-inflammatory and antioxidant activities, inhibits LPS-induced inflammation through the AKT Nrf-2 HO-1-NF-kappaB signaling axis, inhibits TNF-α-induced ICAM-1 and VCAM-1 expression, which can be used to study neurodegenerative diseases.

Polygalasaponin F has anti-neuroinflammatory activity, can inhibit the release of inflammatory cytokines TNF-α and NO induced by lipopolysaccharides (LPS) and reduce the expression of inducible nitric oxide synthases. Polygalasaponin F can significantly i

Calycosin (Cyclosin) acts as a selective estrogen receptor modulator. Calycosin induces apoptosis in human ovarian cancer SKOV3 cells by activating caspases and Bcl-2 family proteins. Calycosin suppresses breast cancer cell growth via ERβ-dependent regulation of IGF-1R, p38 MAPK and PI3K Akt pathways. Calycosin has antineoplastic effects against osteosarcoma through inducing apoptosis showing in vitro and in vivo investigations. Calycosin was shown to induce angiogenesis in human umbilical vein endothelial cell cultures (HUVEC) in vitro. Calycosin may be an effective skin-lightening agent that regulates the expression of melanogenic enzymes. Calycosin exhibited tyrosinase inhibitory activity with an IC(50) value of 38.4 microM.

1. Glaucocalyxin A (Leukamenin F)-SBE-β-CD could be useful with a better solubility and sustained function in drug delivery. 2. Glaucocalyxin A activates caspase-3, decreases BAD phosphorylation, and reduces the expression of X-linked inhibitor of apoptosis protein. 3. Glaucocalyxin A inhibits Akt phosphorylation, suppresses proliferation, and promotes apoptosis in a dose-dependent manner, but not in normal glial cells. 4. Glaucocalyxin A inhibits collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. 5. Glaucocalyxin A could potentially be developed as an antiplatelet and antithrombotic agent, can inhibit platelet p-selectin secretion and integrin activation by convulxin, is a GPVI selective ligand.

1. ISOGINKGETIN (4',4'''-Dimethylamentoflavone), a compound derived from the leaves of Ginkgo biloba, to up-regulate adiponectin secretion with potency comparable to that of rosiglitazone, a known modulator of adiponectin production. 2. Isoginkgetin has anti-tumor activity, the mechanistic basis is splicing inhibition , thus, pre-mRNA splicing inhibitors may represent a novel avenue for development of new anti-cancer agents.3. Isoginkgetin can inhibit tumor cell invasion by regulating phosphatidylinositol 3-kinase Akt-dependent matrix metalloproteinase-9 expression. 4. Isoginkgetin (0.3mg kg ip for 3d) can reduce the level of O2·- in plasma and erythroeyte and sometimes increase the activity of SOD in anoxic rats, the action being stronger than aspirin.

1. Chelidonine (Stylophorin) isolated from Chelidonium majus efficiently induced apoptosis in HeLa cells through possible alteration of p38-p53 and AKT PI3 kinase signalling pathways. 2. Chelidonine is a promising model compound for overcoming MDR and for enhancing cytotoxicity of chemotherapeutics, especially against leukaemia cells, its efficacy needs to be confirmed in animal models. 3. Chelidonine may be a potential therapeutic agent against metastasis of invasive human cancer cells, exhibits antimigratory and antiinvasive effects in MDA-MB-231 cells, by suppressing COL-induced integrin signaling, through inhibiting the formation of the IPP complex and subsequent downregulation of IPP downstream signaling molecules, such as Akt and ERK1 2.

1. Linarin (Acacetin-7-O-rutinoside) (acacetin-7-O-β-d-rutinoside) shows selective dose dependent inhibitory effect on acetylcholinesterase. 2. Linarin alleviates GalN LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways. 3. Linarin prevents A beta-induced neurotoxicity through the activation of PI3K Akt, which subsequently inhibits GSK-3b and up-regulates Bcl-2. 4. The piperine significantly enhanced the oral absorption of Linarin in rats by inhibiting P-glycoprotein mediated cellular efflux during the intestinal absorption and likely simultaneously by inhibiting the metabolism of Linarin.

1. Oroxylin A (Baicalein 6-methyl ether) has various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion. 2. Oroxylin A possesses abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP LIP CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. 3. Oroxylin A inhibits UCP2s triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells; uncoupling protein 2 plays a key role in mitochondrial apoptotic pathway. 4. Oroxylin A inhibits N1ICD translocating to the nucleus and binding to epithelial-mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. 5. Oroxylin A improves the sensitivity of K562 ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K Akt NF-κB pathway, and probably served as a most promising agent for CML treatment.

1. 6-Shogaol (6-Shogaol) has antipyretic and analgesic effects in addition to inhibitory effect on lipoxygenase activity. 2. 6-shogaol has anti-inflammatory property, reduces the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats. 3. 6-Shogaol inhibits the growth of human cancer cells and induces apoptosis in COLO 25 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). 4. 6-Shogaol effectively inhibit invasion and metastasis of hepatocellular carcinoma through diverse molecular mechanisms, including inhibition of the MAPK and PI3k Akt pathways and NF-κB and STAT3 activities to suppress expression of MMP-2 -9 and uPA and block angiogenesis, could further regulate urokinase-type plasminogen activity.

ethyl 2-[3,5-bis(trifluoromethyl)phenyl]-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxylate is a synthetic compound belonging to the curcumin family. It is involved in the regulation of immune response and inflammation through inhibition of the NF-κB signaling pathway, in the regulation of antioxidant response through activation of the Nrf2 signaling pathway, and in the regulation of cell survival and proliferation through inhibition of the Akt signaling pathway.