akt in 1

AKT-IN-1 (AZD-26) is an allosteric AKT inhibitor (IC50: 1.04 μM).

AKT-I-1 is a selective and reversible inhibitor of Akt1.

Akt NF-κB MAPK-IN-1 (compound 2m) is a potent, orally active inhibitor of NO with an IC50 of 7.70 μM and low toxicity, exhibiting anti-inflammatory effects by blocking the Akt NF-κB and MAPK signaling pathways [1].

Akt ROCK-IN-1 (B12) is a dual inhibitor of Akt and ROCK with IC50 values of 0.023 nM and 1.47 nM, respectively, and demonstrates antitumor efficacy against neuroblastoma [1].

PI3K/Akt/CREB Activator 1 is a potent, orally active compound that acts as an activator for the PI3K/Akt/CREB pathway. It enhances neuronal proliferation, induces differentiation of Neuro-2a cells into neuron-like morphology, and accelerates axon-dendrite polarization in primary hippocampal neurons by upregulating brain-derived neurotrophic factor. This compound is utilized in vascular dementia (VaD) research.

Akt mTOR-IN-1 (Compound 8r) is an inhibitor of the AKT mTOR signaling pathway, exhibiting an IC50 of 0.8 µM and possessing anticancer activity. This compound decreases the expression of Caspase 3 while enhancing the expression of the autophagic protein Cyclin B1, thereby inducing autophagy and apoptosis. Akt mTOR-IN-1 is applicable for research in the field of non-small cell lung cancer (NSCLC).

PI3K/AKT-IN-1 is a potent, dual PI3K/AKT inhibitor that acts on PI3Kγ (IC50: 6.99 μM), PI3Kδ (IC50: 4.01 μM) and AKT (IC50: 3.36 μM). PI3K/AKT-IN-1 induces caspase 3-dependent apoptosis by inhibiting the PI3K/AKT pathway. caspase 3-dependent apoptosis and exhibited anticancer effects.

EGFR Akt-IN-1 (compound 17) serves as an effective inhibitor of EGFR Akt, exhibiting IC50 values of 12.89 μM and 10.88 μM in A549 cells, respectively. This compound induces cell cycle arrest at the S phase.

APN AKT-IN-1 is a potent dual inhibitor of aminopeptidase N (APN) and protein kinase B (AKT), with IC50 values of 0.21 μM for APN and 0.27 μM for AKT inhibition. The compound effectively suppresses the phosphorylation of glycogen synthase kinase 3 beta (GSK3β), an intracellular substrate of AKT [1].

Akt NF-κB JNK-IN-1 (Compound 2i) is an inhibitor of the Akt, NF-κB, and JNK signaling pathways, demonstrating inhibition of nitric oxide production (IC50: 3.15 μM) and exhibiting anti-inflammatory effects.

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.

Akt3 degrader 1 is a specific Akt3 degrader with anticancer and antiproliferative activity that inhibits tumor growth in mice.Akt3 degrader 1 is used in the study of non-small cell lung cancer and pancreatic cancer.

Akt1 and Akt2-IN-1 is an allosteric inhibitor of Akt1 (IC50=3.5 nM) and Akt2 (IC50=42 nM). It has potent and balanced activity.

Tubulin AKT1-IN-1 (Compound D1-1) is an inhibitor of tubulin polymerization and AKT pathway activation, suppressing proliferation and metastasis of H1975 cells while modestly inducing apoptosis. The compound is used in studying non-small-cell lung cancer (NSCLC) [1].

TAT-TCL1-Akt-in functions as an Akt inhibitor [1].

Akt1&PKA-IN-1 is a potent dual inhibitor of Akt and PKA, with IC50 values of 0.11 μM for Akt, 0.03 μM for PKAα, and 9.8 μM for CDK2, demonstrating selective inhibition of cyclin-dependent kinase 2 (CDK2).

Akt1-IN-1 is a potent and selective inhibitor of Akt1, demonstrating an IC50 of 18.79 nM in MIA PaCa-2 cells, indicating its high efficacy in inhibiting this specific kinase. Notably, it shows no significant teratogenicity, hepatotoxicity, or cardiotoxicity (No Observed Adverse Effect Level > 100 µM), making it a viable candidate for anticancer research.

Akt1&PKA-IN-2 ((R)-29), a compound specific to PKB AKT and selective for cyclin-dependent kinase 2 (CDK2), effectively inhibits AKT1, PKAa, and CDK2a with IC50 values of 0.007 µM, 0.01 µM, and 0.69 µM, respectively.

Akt1-IN-4 (Compound 62) serves as an inhibitor of AKT1-E17K, exhibiting potent activity with an IC50 value below 15 nM [1].

Akt1-IN-3 (Compd 7) serves as an AKT1 inhibitor, specifically targeting AKT1-E17K with an IC50 of less than 15 nM [1].

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.

Caffeic Acid Phenethyl Ester (Phenylethyl Caffeate) (CAPE) inhibits the activation of nuclear transcription factor NF-kappa B and may suppress p70S6K and Akt-driven signaling pathways, with antineoplastic, cytoprotective and immunomodulating activities. CAPE is the phenethyl alcohol ester of caffeic acid and a bioactive component of honeybee hive propolis. In addition, CAPE inhibits PDGF-induced proliferation of vascular smooth muscle cells through the activation of p38 mitogen-activated protein kinase (MAPK) and hypoxia-inducible factor (HIF)-1alpha and subsequent induction of heme oxygenase-1 (HO-1).

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.

A-674563 is an orally available, ATP-competitive, and reversible inhibitor of Akt (Ki: 11 nM for Akt1) [1]. It exhibits inhibitory activity against PKA and Cdk2 (IC50: 16 46 nM) but is 10- to >1, 800-fold selective for Akt1 versus additional kinases in th

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.

Cucurbitacin B (Cuc B) has profound in vitro and in vivo antiproliferative effects against human pancreatic Y cells. It inhibited AKT signaling activation through up-regulation of PTEN. Cucurbitacin B is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity. Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung Y cells.

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.

Dihydrocapsaicin (CCRIS1589) is isolated from Capsicum fruit. Capsaicin is the primary active component of the heat and pain-eliciting lipid soluble fraction of the Capsicum pepper. Like capsaicin, dihydrocapsaicin is an irritant. Capsaicin is found in natural hot pepper extracts along with a number of impurities, including dihydrocapsaicin and several lesser impurities. Separation by HPLC is required in order to obtain pure dihydrocapsaicin. Dihydrocapsaicin represents about 10% of the compound present in commercial preparations purporting to be pure capsaicin, but it has about the same pungency as capsaicin. VR1 (vanilloid receptor 1) is a heat activated calcium ion channel which functions as a part of the normal nociceptive pain pathway. Capsaicin elicits a sensation of burning pain by activation of VR1 on small, non-myelinated polymodal C-type nociceptive nerve fibers. The potency of dihydrocapsaicin at VR1 appears equivalent to capsaicin. Antioxidant. Reduces oxidation of serum lipids. Mutagenic. Dihydrocapsaicin is an activator of VR1.

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. 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.

API-1 (NSC-177223) is a potent inhibitor of Akt. It induces GSK3-dependent, β-TrCP- and FBXW7-mediated Mcl-1 degradation, resulting in induction of apoptosis .

CAY10404 (3-(4-METHYLSULPHONYLPHENYL)-4-PHENYL-5-T) is a potent and highly selective inhibitor of COX-2 and COX-1. It is also a potent inhibitor of PKB Akt and MAPK signalling pathways and induces apoptosis in NSC-LC cells, with analgesic, anti-inflammatory and anti-cancer activities.

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.

Phellopterin is a partial agonist of the central benzodiazepine receptors in vitro. Phellopterin shows a cytotoxic effect on RAW264.7 cell at the concentration from 40 to 400 μM. Phellopterin reduce TNF-alpha-induced VCAM-1 expression through regulation o

Cyclo(L-Phe-L-Val) is a metabolite of the sponge bacterium Pseudoalteromonas sp. NJ6-3-1, capable of autoinducing the production of antibacterial substances active against S. aureus at low cell density. It induces neurite outgrowth and branching of chick cortical neurons in vitro at concentrations of 16 and 32 μM, increases phosphorylation of the PI3K substrate Akt, and this induction can be blocked by the PI3K inhibitor LY294002. Additionally, it enhances axon sprouting of calcitonin gene-related protein positive (CGRP+) primary afferents in the spinal cord post-crush injury and of serotonin neurons in the uninjured spinal cord. Cyclo(L-Phe-L-Val) is also a bitter taste component of cocoa and roasted coffee.

PtdIns-(3,4,5)-P3 (PIP3) serves as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains such as phosphatidylinositol 3-kinase (PI3K) or PTEN. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking and initiates an intricate signaling cascade that has been implicated in cancer. 3,5-dimethyl PIT-1 is a dimethyl analog of PIT-1, the selective inhibitor of PIP3/Akt PH domain binding, that is designed for more favorable solubility in vivo. 3,5-dimethyl PIT-1 inhibits PI3K/Akt signaling (IC50 = 27 μM), suppressing PI3K-PDK1-Akt-dependent phosphorylation, which has been shown to reduce cell viability and induce apoptosis in PTEN-deficient U87MG glioblastoma cells (IC50 = 36 μM). 4T1 breast cancer growth is significantly attenuated in BALB/c mice with a dose of 1 mg/kg of 3,5-dimethyl PIT-1 per day.

YF704 (compound 4w), a selective allosteric inhibitor of SHP2, exhibits antiproliferative effects and induces apoptosis in cancer cells with an IC50 of 0.25 μM. Furthermore, it downregulates Erk1/2 and Akt phosphorylation levels in cancer cells [1].

Ganglioside GM3 is a monosialoganglioside that demonstrates antiproliferative and proapoptotic effects in tumor cells by modulating cell adhesion, proliferation, and differentiation. It suppresses angiogenesis and reduces proliferation and migration of human umbilical vein endothelial cells (HUVECs) when used at a concentration of 20 μM via inhibition of VEGFR2 and Akt phosphorylation. Ganglioside GM3 induces dissociation of the insulin receptor-caveolin-1 complex from lipid microdomains, functioning as an inhibitor of insulin signaling and contributing to insulin resistance in adipocytes. Ganglioside GM3 mixture contains ganglioside GM3 molecular species with C18:1 and C20:1 fatty acyl chains.

Lenalidomide-C9-aldehyde is a synthesized E3 ligase ligand-linker conjugate that incorporates the Lenalidomide based cereblon ligand and a linker. Lenalidomide-C9-aldehyde can be used in the synthesis of a series of PROTACs, such as INY-03-041. INY-03-041

KP372-1 is an Akt inhibitor that blocks signaling through the PI3K pathway, inhibiting cell proliferation while inducing apoptosis and anoikis in squamous cell carcinoma of the head and neck.

22-(4′-py)-JA, a semisynthetic derivative of junamycin A isolated from the Thai blue sponge (Xestospongia sp.), exhibits antimetastatic properties by inhibiting the AKT/mTOR/p70S6K signaling pathway. It also impedes tumor cell invasion and angiogenesis in human umbilical vein endothelial cells (HUVEC), while suppressing the expression of metalloproteinases (MMP-2 and MMP-9), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF). Its potent anticancer activity is particularly noted against non-small cell lung cancer (NSCLC) [1].

AKT-IN-7 (compound 1-P1) is a potent AKT inhibitor with potential applications in cancer research.

1-O-Octadecyl-2-O-methyl-sn-glycerol is a metabolite of a phosphotidylinositol ether lipid analog (PIA). PIAs are known to target the pleckstrin homology domain of the serine/threonine kinase Akt and to induce apoptosis in cancer cell lines with high levels of endogenous Akt activity.

Monascuspiloin is a fungal metabolite that has been found inM. pilosusM93-fermented rice.1It induces endoplasmic reticulum stress and autophagy in PC3 prostate cancer cells. Monascuspiloin (15-45 μM) decreases viability of PC3 cells and has an additive effect on the reduction in viability of PC3 cells induced by irradiation when used at a concentration of 25 μM. It induces intratumor apoptosis and autophagy and reduces tumor growth in a PC3 mouse xenograft model when administered at doses of 40 and 120 mg/kg.2 1.Chiu, H.-W., Fang, W.-H., Chen, Y.-L., et al.Monascuspiloin enhances the radiation sensitivity of human prostate cancer cells by stimulating endoplasmic reticulum stress and inducing autophagyPLoS One7(7)e40462(2012) 2.Chen, R.-J., Hung, C.-M., Chen, Y.-L., et al.Monascuspiloin induces apoptosis and autophagic cell death in human prostate cancer cells via the Akt and AMPK signaling pathwaysJ. Agric. Food Chem.60(29)7185-7193(2012)