pi3k/akt

PI3K Akt mTOR-IN-2 is a potent PI3K AKT mTOR inhibitor.PI3K Akt mTOR-IN-2 has anticancer effects and is selective for MDA-MB-231 cells with an IC50 of 2.29 μM.PI3K Akt mTOR-IN-2 exhibits anticancer activity and induces cycle arrest and apoptosis in cancer cells. PI3K Akt mTOR-IN-2 has anticancer activity and can induce cycle arrest and apoptosis in 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-IN-C89 is a novel Inhibitor of the PI3K-Akt Pathway, Inducing Autophagy of Female Germline Stem Cells.

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.

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.

PI3K/Akt/mTOR-IN-3 is a potent inhibitor of PI3K/Akt/mTOR. PI3K/Akt/mTOR-IN-3 inhibits the migration of MCF-7 cells (IC50: 0.77 μM), HeLa cells (IC50: 1.23 μM) and HepG2 cells (IC50: 4.57 μM). PI3K/Akt/mTOR-IN-3 inhibited the migration of MCF-7 and HeLa cells at a concentration of 4 μM. PI3K/Akt/mTOR-IN-3 blocked the cell cycle in S phase and induced apoptosis.

PI3K/mTOR Inhibitor-3 (compound 12) is an imidazoline compound with potent dual inhibitory effects on PI3K and mTOR. This compound exhibits notable anti-cancer activity [1].

Heterocyclic compounds as covalent inhibitors of G12C mutant K-Ras protein useful for treating cancers.K-Ras G12C-IN-3 is a novel and irreversible inhibitor of mutant K-ras G12C.

K 259-3, a methyl ester of K 259-2, is an inhibitor of calmodulin-dependent cyclic nucleotide phosphodiesterase.

Cathepsin K Inhibitor 3, exhibiting an IC50 value of 0.5 nM, is a highly selective inhibitor of cathepsin K, featuring a favorable pharmacokinetic profile. It holds potential for use in studies of osteoarthritis (OA).

K-Ras ligand-Linker Conjugate 3 (Compound 001371) is a chemical compound that consists of a ligand for K-Ras recruiting moiety and a PROTAC linker, responsible for recruiting E3 ligases (e.g., VHL, CRBN, MDM2, and IAP). This compound is essential in the synthesis of PROTAC K-Ras Degrader-1, a potent PROTAC K-Ras degrader that demonstrates a degradation efficacy of ≥70% in SW1573 cells[1].

AKT-IN-3 is a potent, orally active low hERG blocking Akt inhibitor (IC50: 1.4 nM, 1.2 nM, and 1.7 nM for Akt1, Akt2, and Akt3). AKT-IN-3 (compound E22) also exhibits good inhibitory activity against other AGC family kinases, such as PKA, PKC, ROCK1, RSK1

Alpelisib (BYL-719) is a PI3Kα inhibitor (IC50=5 nM) with selective, potent, and oral activity. Alpelisib inhibits PI3Kβ/γ/δ with low activity (IC50=250/290/1200 nM). Alpelisib has antitumor activity and is targeted to PIK3CA mutant tumors.

Bilobalide ((-)-Bilobalide), a bioactive from Gingko Biloba, is active on hypoxia-induced alterations.

Sophocarpine monohydrate, a major ingredient of Sophora alopecuroides, has a wide range of pharmacological effects.

4-Hydroxybenzyl alcohol (P-Methylolphenol) exhibits beneficial effects in cerebral ischemic injury, has neuroprotective effect through upregulation of Nrf2, Prdx6, and PDI expression via the PI3K/Akt pathway. 4-Hydroxybenzyl alcohol inhibit the development of new blood vessels by targeting multiple mechanisms of the angiogenic process, may as a promising candidate for the establishment of anti-angiogenic treatment strategies in cancer therapy.

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.

3'-Hydroxypterostilbene (3'-HPT), a natural pterostilbene analogue, effectively inhibits the growth of human colon cancer cells with IC50s of 9.0, 40.2, and 70.9 μM for COLO 205, HCT-116, and HT-29 cells, respectively, by inducing apoptosis and autophagy. 3'-Hydroxypterostilbene inhibits the p38MAPK , and PI3K/Akt/mTOR/p70S6K pathways and activates the ERK1/2, JNK1/2 MAPK pathways[1].

Musk ketone can induce the growth repression and the apoptosis of cancer cells. Musk ketone increases activity of glutathione S-transferase and thus may prove to be useful cancer chemoprotectant.

Torbafylline, a xanthine derivative, is a phosphodiesterase (PDE) inhibitor that attenuates burn-induced protein hydrolysis in rat skeletal muscle through activation of the PDE4 cAMP EPAC PI3K Akt pathway, and inhibits the enhanced ubiquitin-proteasome-dependent protein hydrolysis in skeletal muscle of cancer- and sepsis-prone rats.

Phellamurin inhibits intestinal P-glycoprotein in a dose-dependent manner, there is a serious interaction occurred between Phellamurin with cyclosporin, to ensure the efficacy of cyclosporin, we suggest that the coadministration of Phellamurin or Phellode

Protectin D1 (Neuroprotectin D1) is a neuroprotectin produced by neuronal cells and is a potential cardioprotective agent.Protectin D1 attenuates myocardial ischemia/reperfusion injury and inhibits imiquimod-induced psoriasis-like skin inflammation by modulating the PI3K/AKT signaling pathway.

RTC-5 (TRC-382) is a phenothiazine compound that has been specifically enhanced for its potent anti-cancer properties. It exhibits considerable effectiveness against an EGFR-driven cancer xenograft model. The mechanism behind its efficacy can be attributed to the simultaneous inhibition of PI3K-AKT and RAS-ERK signaling pathways.

Cichoric Acid (Dicaffeoyltartaric acid) is a potent inhibitor of human immunodeficiency virus type-1 (HIV-1) integrase and the replication in tissues. It also a class of cannabinomimetics with CB2 receptor-dependent and independent.

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.

Sincalide (CCK-8) is a cholecystokinetic drug administered by injection to aid in diagnosing disorders of the gallbladder and pancreas. It is the 8-amino acid C-terminal fragment of cholecystokinin.

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

Oroxin B (Hypocretin-2) has antioxidant activity.

Amarogentin is mainly extracted from Swertia and Gentiana roots. It plays cemopreventive therapeutic role during liver carcinogenesis through modulation of cell cycle and apoptosis

Miransertib (ARQ-092) is an orally bioavailable, selective, and potent allosteric Akt inhibitor.

Fimepinostat (CUDC 907) is an orally bioavailable inhibitor of both phosphoinositide 3-kinase (PI3K) class I and pan-histone deacetylase (HDAC) enzymes, with potential antineoplastic activity. Upon oral administration, CUDC-907 inhibits the activity of both PI3K class I isoforms and HDAC, thereby preventing the activation of the PI3K-AKT-mTOR signal transduction pathway that is often overactivated in many cancer cell types.

α-Linolenic acid (Alpha-Linolenic Acid) is an essential fatty acid belonging to the omega-3 fatty acids group. It is highly concentrated in certain plant oils and has been reported to inhibit the synthesis of prostaglandin resulting in reduced inflammation and prevention of certain chronic diseases.

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.

Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) is an ATP-competitive pan-class I PI3K inhibitor (IC50s: 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ). Copanlisib dihydrochloride has superior antitumor activity and it also has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR.

Deguelin ((-)-Deguelin) is a PI3K AKT Inhibitor, which is a natural product isolated from plants in the Mundulea sericea family.

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.

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.

Isolongifolene ((-)-Isolongifolene), a tricyclic sesquiterpene isolated from Murraya koenigii, exhibits antioxidant, anti-inflammatory, anticancer, and neuroprotective properties. It mitigates Rotenone-induced oxidative stress, mitochondrial dysfunction, and apoptosis by modulating the PI3K/AKT/GSK-3β signaling pathways.

Polygalacin D shows anti- proliferation, anti-inflammary, and hepatoprotective activities, it can inhibit the expression of lipopolysaccharide (LPS)-induced iNOS and COX-2 protein and mRNA without an appreciable cytotoxic effect on RAW 264.7 macrophages, and can suppress induction by LPS of pro-inflammatory cytokines such as prostaglandin E2 (PGE2).

Copanlisib (BAY 80-6946) is a phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. Copanlisib inhibits the activation of the PI3K signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.

Ridaforolimus (AP23573) is a small molecule and non-prodrug analogue of the lipophilic macrolide antibiotic rapamycin with potential antitumor activity. Ridaforolimus binds to and inhibits the mammalian target of rapamycin (mTOR), which may result in cell cycle arrest and, consequently, the inhibition of tumor cell growth and proliferation. Upregulated in some tumors, mTOR is a serine/threonine kinase involved in regulating cellular proliferation, motility, and survival that is located downstream of the PI3K/Akt signaling pathway.

Nimbolide suppresses CDK4/CDK6 kinase activity. Nimbolide inhibits the NF-κB, Wnt, PI3K-Akt, MAPK, and JAK-STAT signaling pathways. Nimbolide causes apoptosis through the inactivation of NF-κB. Nimbolide is a triterpene derived from the leaves and flowers

Esculetin (Cichorigenin) is a coumarin derivative from various natural plant products with various biological and pharmaceutical properties including anti-edema, anti-inflammatory and anti-tumour effects. It inhibits lipoxygenases (LOs).

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.

Minocycline hydrochloride (Minocycline HCl) is a tetracycline antibiotic with excellent absorption and tissue penetration that is used for several bacterial infections as well as treatment of acne. Minocycline hydrochloride can cause both an acute hepatitis-like syndrome occurring within 1 to 3 months of starting therapy or a more insidious chronic hepatitis with autoimmune features typically after long-term 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.

P7C3-A20 is a derivative of P7C3 that has proneurogenic and neuroprotective activity.

Biatractylolide has a neuroprotective effect on glutamate-induced injury in PC12 and SH-SY5Y cells through a mechanism of the PI3K-Akt-GSK3β-dependent pathways. The molecular mechanisms of inhibitory activities of biatractylolide on AChE are not only thro

Clematichinenoside AR exerts anti-inflammatory and immunosuppressive properties, it has anti-arthritic effects on PI3K Akt signaling pathway and TNF-α± associated with collagen-induced arthritis.

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)