akt-in-6

AKT-IN-6 (INCB-047775) has an inhibitory effect on ATK. Akt is an important component of cellular signaling for growth factors, cytokines, and other cell stimuli. Abnormal Akt activation has been associated with the development of type 2 diabetes mellitus and cancer.

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.

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)

c-MET degrader. Comprises MET inhibitor foretinib (GSK 1363089; Cat. No. 6056) joined by a linker to a von Hippel-Lindau (VHL) recruiting ligand. Degrades c-MET within 6 hours in vitro. Inhibits agonist-driven AKT phosphorylation and GTL16 cell proliferation (IC50 = 66.7 nM). Also degrades exon-14-deleted c-MET in Hs746T cells.

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.

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].

CHMFL-PI3KD-317 is a highly potent, selective and orally active PI3Kδ inhibitor, with an IC50 of 6 nM, and exhibits over 10-1500 fold selectivity over other class I, II and III PIKK family isoforms, such as PI3Kα (IC50, 62.6 nM), PI3Kβ (IC50, 284 nM), PI3Kγ (IC50, 202.7 nM), PIK3C2A (IC50, >10000 nM), PIK3C2B (IC50, 882.3 nM), VPS34 (IC50, 1801.7 nM), PI4KIIIA (IC50, 574.1 nM) and PI4KIIIB (IC50, 300.2 nM). CHMFL-PI3KD-317 inhibits PI3Kδ-mediated Akt T308 phosphorylation in Raji cells, with an EC50 of 4.3 nM. CHMFL-PI3KD-317 has antiproliferative effects on cancer 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). It exhibits anti-tumor activity in mouse glioblastoma xenograft model[1]. AMG 511 significantly suppresses PI3K

BX795 is an effective and selective PDK1 inhibitor (IC50: 6 nM), and its selectivity is 140- and 1600-fold for PDK1 over PKA and PKC in cell-free assays, respectively. Meanwhile, the selectivity for PDK1 is 100-fold than GSK3β.

PI3K/mTOR Inhibitor-6 (Compound 19c) is a potent dual PI3K/mTOR inhibitor that is more stable than gedatolisib in artificial gastric fluid. 10 μM of PI3K/mTOR Inhibitor-6 significantly inhibits the PI3K/Akt/mTOR signalling pathway. PI3K/mTOR Inhibitor-6 has shown potential for research in cancer diseases.

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].

6-Hydroxyflavone (6-HF) is a noncompetitive inhibitors of cytochrome P450 2C9. It is a flavone, a type of chemical compound. It is reported in leaves of Barleria prionitis Linn. (a common Acanthaceae from India). 6-Hydroxyflavone may have a potential as a therapeutic drug capable for the treatment of anxiety-like disorders.

Tricetin is a flavonoid isolated from pomegranate.Tricetin is a potent competitive inhibitor of Keap1-Nrf2 protein-protein interaction (PPI) and protects Parkinson's disease patients from 6-OHDA-induced neurotoxicity by activating the Nrf2/HO-1 signaling pathway and blocking mitochondria-dependent apoptotic pathways.Tricetin Inhibits migration and expression of the indicator protease progerin-1 (PS-1) in nasopharyngeal carcinoma through the Akt/GSK-1β pathway.Tricetin inhibits endothelial inflammation induced by oxidized LDL mediated by Egr-1, and protects rat chondrocytes from IL-1β-induced inflammation and apoptosis.Tricetin is an inhibitor of endothelial inflammation induced by oxidized LDL mediated by Egr-1 and protects against IL-1β-induced inflammation and apoptosis.

2-Amino-5-bromo-6-chloropyrazine is a heterocyclic building block.1,2It has been used in the synthesis of Akt inhibitors. 1.Kettle, J.G., Brown, S., Crafter, C., et al.Diverse heterocyclic scaffolds as allosteric inhibitors of AKTJ. Med. Chem.55(3)1261-1273(2012) 2.Goel, R., Luxami, V., and Paul, K.Recent advances in development of imidazo[1,2-a]pyrazines: Synthesis, reactivity and their biological applicationsOrg. Biomol. Chem.13(12)3525-3555(2015)

ASK120067 is a potent and orally active inhibitor of EGFRT790M (IC50:0.3 nM) with selectivity over EGFRWT (IC50:6.0 nM). ASK120067 is a third-generation EGFR-TKI for the research of non-small cell lung cancer (NSCLC)[1]. In the in vitro kinase assay ASK120067 potently inhibits the EGFR L858R/T790M and EGFR T790M resistant mutants with IC50 values of 0.3 nM and 0.5 nM, respectively, as well as the EGFRexon19del sensitizing mutant (IC50= 0.5 nM). The 50 of ASK120067 against wild-type EGFR (EGFRWT) is 6 nM[1].ASK120067 selectively inhibits the growth of EGFR-mutant cell lines and exhibits potent antiproliferative activity in the mutant EGFR NSCLC cells, with IC50 values of 12 nM, 6 nM and 2 nM against NCI-H1975 (T790M mutation), PC-9, and HCC827 cells (sensitizing mutations), respectively. However, it shows moderate or weak anti-growth activities in A431, LoVo and A549 cells (EGFRWT), with IC50 values ranging from 338 nM to 1541 nM[1].ASK120067 (0.1-100 nM) inhibits the phosphorylation of EGFR at Tyrosine residue 1068 and its downstream signaling proteins AKT and ERK in NCI-H1975 cells (EGFRL858R/T790M) even at low dosage (0.1-1 nM). Additionally, ASK120067 inhibits p-EGFR and p-Akt and p-erk in EGFR WT A431 cell until the concentration reaches 10 to 100 nM[1]. ASK120067 (oral gavage; 5-20 mg/kg; once daily; 21 days) results in significantly regressed tumor growth, with a tumor growth inhibition (TGI) rate of 85.7%, and administration of 10 mg/kg ASK120067 causes dramatic tumor shrinkage with a TGI rate of 99.3%, exhibiting a similar potency with Osimertinib[1]. [1]. Tao Zhang, et al. Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance. Mol Cancer. 2020 May 13;19(1):90.

Teprotumumab is a human monoclonal antibody that blocks the IGF-1 receptor (IGF-1R). Teprotumumab binds to the extracellular α-subunit domain ligand of IGF-1R. Teprotumumab inhibits TSH and IGF-1 action in fibrocytes. Teprotumumab reduces TSH-dependent IL-6 and IL-8 expression and Akt phosphorylation. Teprotumumab can be used in the study of thyroid-associated eye diseases.

PDMP is a ceramide analog first prepared in a search for inhibitors of glucosylceramide synthase. PDMP has two adjacent chiral centers (C1 and C2) allowing for the formation of four possible isomers. PDMP contains all four of these stereoisomers. PDMP inhibits glucosylceramide synthase by 90% when used at a concentration of 0.8 μM in MDCK cell homogenates, however, the ability to inhibit glucosylceramide synthase has been found to reside in the D-threo (1R,2R) enantiomer. The D-threo PDMP enantiomer is also responsible for inhibition of β-1,4-galactosyltransferase 6 and prevention of lactosylceramide synthesis, which is a promotor of neuroinflammation in mice during chronic experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. PDMP enhances curcumin-induced inhibition of proliferation, JNK activation, and Akt inhibition, as well as induction of apoptosis in WM-115 melanoma cells in vitro.

1. Crebanine iv 5mg/kg can eonvert BaCl_2-induced arrhythmia into sinus rhythm in rats, and can significantly increase the tolerant dose of aconitine to produce ventrieular fibrillation(VF) and cardiac arrest (CA) in rata. 2. Crebanine can also decrease t

Nephrin is a cell surface signaling receptor protein that regulates podocyte function and plays a role in β-cell survival signaling; it is a protein necessary for the proper functioning of the renal filtration barrier. Nephrin belongs to a family of highl