pi3k-in-6

PI3K-IN-6 is an oral active and highly selective inhibitor of phosphoinositide 3-kinase (PI3K) β δ(IC50 values of 7.8 nM 5.3 nM , respectively).

PI3Kα-IN-6 (Compound 5b) is a PI3Kα inhibitor that demonstrates anticancer properties without harming normal cells, by increasing ROS production, decreasing mitochondrial membrane potential, and inducing apoptosis.

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.

Rhodiolin, a natural product from Rhodiola rosea, blocks glycolysis of glucose 6-phosphate isomerase (GPI) in human papillary thyroid cancer (PTC), inhibits phosphorylation of the PI3K AKT mTOR signaling pathway and induces apoptosis of PTC cells.

AMG 511 is a potent and orally available pan inhibitor of class I PI3Ks (Kis of 4 nM, 6 nM, 2 nM, and 1 nM for PI3Kα, β, δ, and γ, respectively), exhibiting anti-tumor activity in a mouse glioblastoma xenograft model[1]. AMG 511 significantly suppresses PI3K signaling as indicated by a decrease in p-Akt (Ser473).

Aflatoxin B2-13C17(AFB2-13C17) is intended for use as an internal standard for the quantification of AFB2by GC- or LC-MS. AFB2is a mycotoxin that has been found inA. terricola.1It induces hepatic autophagy and apoptosis in broiler chickens when administered at doses of 0.2, 0.4, and 0.8 mg/kg.2AFB2(0.5 and 1 mg/animal) also induces parenchymal cell hyperplasia in rats.3 1.Moubasher, A.H., el-Kady, I.A., and Shoriet, A.Toxigenic Aspergilli isolated from different sources in EgyptAnn. Nutr. Aliment.31(4-6)607-615(1977) 2.Chen, B., Li, D., Li, M., et al.Induction of mitochondria-mediated apoptosis and PI3K/Akt/mTOR-mediated autophagy by aflatoxin B2 in hepatocytes of broilersOncotarget7(51)84989-84998(2016) 3.Wogan, G.N., Edwards, G.S., and Newberne, P.M.Structure-activity relationships in toxicity and carcinogenicity of aflatoxins and analogsCancer Res.31(12)1936-1942(1971)

TBK1 IKKε-IN-4, a 6-aminopyrazolopyrimidine derivative, serves as a potent, selective inhibitor for TBK1 and IKKε, demonstrating IC50 values of 13 nM and 59 nM, respectively. This compound exhibits significantly reduced activity, by 100- to 1000-fold, against other protein kinases, such as PDK1, PI3K family members, and mTOR[1].

PI3K-IN-26 is an effective PI3K inhibitor. PI3K-IN-26 inhibits the proliferation of SU-DHL-6 cells, IC50= 36 nM.

HDAC-IN-43 is a potent HDAC 1 3 6 inhibitor with IC50 values of 82 nM for HDAC 1, 45 nM for HDAC 3, and 24 nM for HDAC 6, and a weak PI3K mTOR inhibitor with IC50 values of 3.6 μM for PI3K and 3.7 μM for mTOR, exhibiting a broad-spectrum anti-proliferative effect.

PI3K-IN-37 (Example 84.1) is an inhibitor of PI3K α (IC50: 6 nM), PI3K β (IC50: 8 nM), and PI3K δ (IC50: 4 nM), and also inhibits mTOR with an IC50 of 4 nM.

PI3K mTOR Inhibitor-6 (Compound 19c) is a potent dual PI3K mTOR inhibitor, exhibiting greater stability than gedatolisib in artificial gastric fluid. At 10 μM, PI3K mTOR Inhibitor-6 significantly inhibits the PI3K Akt mTOR signaling pathway and has shown potential for cancer research.

6-O-Isobutyrylbritannilactone, a sesquiterpene natural melanogenesis inhibitor, can be extracted from Inula britannica flowers. It effectively suppresses IBMX-induced melanin production in B16F10 cells and exerts antimelanogenic effects in zebrafish embryo models by modulating ERK, PI3K AKT, and CREB pathways [1].

PI3Kδ-IN-17 (Compound S5) is a potent PI3K δ inhibitor with an IC50 value of 2.82 nM, significantly inhibiting SU-DHL-6 cell proliferation with an IC50 of 0.035 μM [1].

Anticancer agent 109 (compound 6-15) acts as an inhibitor targeting the Gas6-Axl axis, demonstrating significant anti-cancer properties. This compound suppresses the expression of Gas6, Axl, p-PI3K, and p-AKT in cancer cells, thereby inducing G1 phase arrest and promoting apoptosis of cancer cells. Additionally, Anticancer agent 109 effectively inhibits tumor growth in nude mouse tumor-bearing models [1].

Compound 19, also known as Antidiabetic agent 6, is an antidiabetic compound. It stimulates the translocation of GLUT4 by activating the PI3K AKT-dependent signaling pathway. Furthermore, this compound reduces blood glucose levels in diabetic rats induced by streptozotocin.