N-Methylhemeanthidine chloride is an amaryllidaceae alkaloid isolated from Zephyranthes candida. N-Methylhemeanthidine chloride has antitumor activity and can inhibit cancer cell proliferation by down-regulating < a href=" " class="link-product" target="_blank">AKT activation, mediating cell cycle arrest and inducing < a href=" " class="link-product" target="_blank">apoptosis[1].
AKT-IN-7 (compound 1-P1) is a potent AKT inhibitor. AKT-IN-7 has the potential for cancer research[1].
(E)-Akt inhibitor-IV ((E)-AKTIV) is a PI3K-Akt inhibitor, with potent cytotoxic[1].
Albanol B is an arylbenzofuran derivative which can be isolated from mulberries. Albanol B exhibits anti-Alzheimer's disease, anti-bacterial and antioxidant activities. Albanol B inhibits cancer cells proliferation, down-regulates CDK1 expression. Albanol B also induces cell cycle arrest at G2/M and apoptosis. And Albanol B induces mitochondrial ROS production and increases the phosphorylation levels of AKT and ERK1/2[1].
Esculetin is an active ingredient extracted mainly from the bark of Fraxinus rhynchophylla. Esculetin inhibits platelet-derived growth factor (PDGF)-induced airway smooth muscle cells (ASMCs) phenotype switching through inhibition of PI3K/Akt pathway. Esculetin has antioxidant, antiinflammatory, and antitumor activities[1].
Z-guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, inhibits the growth of human prostate cancer cells by causing apoptosis. Z-guggulsterone inhibits angiogenesis by suppressing the VEGF–VEGF-R2–Akt signaling axis[1].
CHPG sodium salt is a selective mGluR5 agonist, and attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells[1]. CHPG sodium salt protects against traumatic brain injury (TBI) in vitro and in vivo by activation of the ERK and Akt signaling pathways.[2].
N-Feruloyloctopamine, isolated from Garlic skin, is an antioxidant constituent. N-Feruloyloctopamine significantly decreases the phosphorylation levels of Akt and p38 MAPK[1].
M2698 (MSC2363318A) is an orally active, ATP competitive, selective p70S6K and Akt dual-inhibitor with IC50s of 1 nM for p70S6K, Akt1 and Akt3. M2698 can cross the blood-brain barrier and has anti-cancer activity[1].
Theaflavin 3,3'-digallate (TF3), the typical pigment in black tea, is a good antitumor agent. Theaflavin 3,3'-digallate is generally regarded as the effective component for the inhibitory effects against carcinogenesis without adverse side effects by affecting multiple signal transduction pathways, such as upregulating p53 and p21, inhibiting phosphorylation of the cell survival protein Akt and MAPK pathway, downregulation of NF-κB, shifting the ratio between pro-/antiapoptotic proteins. Theaflavin 3,3'-digallate causes a rapid and sustained decrease in phospho-ERK1/2 and -MEK1/2 protein expression. Theaflavin 3,3'-digallate inhibits HCT116 cell growth with an IC50 of 17.26 μM[1].
AKT-IN-14 (Example 2) is a potent AKTinhibitor with the IC50 values of <0.01 nM, 1.06 nM and 0.66 nM for AKT1, AKT2, AKT3, respectively. AKT-IN-14 can be used in cancer research[1].
ALM301 is an orally active highly specific AKT inhibitor with IC50 values of 0.13 µM, 0.09 µM and 2.75 µM for AKT1, AKT2 and AKT3, respectively. ALM301 inhibits AKT phosphorylation and modulates downstream signalling in vitro. ALM301 can inhibit cancer cell proliferation and tumor growth[1].
DCZ3301 is a potent aryl-guanidino inhibitor. DCZ3301 inhibits cell proliferation, induces G2/M cell cycle arrest and apoptosis. DCZ3301 inhibits the activation of the PI3K/AKT pathway by downregulating the protein expression of PI3K and phosphorylation of AKT. DCZ3301 can be used in research of cancer[1].
Crebanine, an alkaloid from Stephania venosa, induces G1 arrest and apoptosis in human cancer cells. Crebanine exhibits anti-inflammatory activity via suppressing MAPKs and Akt signaling. Crebanine also possesses antiarrhythmic effect[1][2].
TCL1(10-24) is a encompassing the betaA strand of human TCL1. TCL1(10-24) is a Akt inhibitor. TCL1(10-24) interacts with the Akt PH domain prevented phosphoinositide binding and hence inhibits membrane translocation and activation of Akt. TCL1(10-24) inhibits cellular proliferation and anti-apoptosis. TCL1(10-24) has tumor growth in vivo[1].
Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. Paris saponin VII-induced apoptosis in K562/ADR cells is associated with Akt/MAPK and the inhibition of P-gp. Paris saponin VII attenuates mitochondrial membrane potential, increases the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decreases the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia[1].
CCT128930 hydrochloride is a potent and selective inhibitor of AKT (IC50=6 nM). CCT128930 hydrochloride has 28-fold selectivity over the closely related PKA kinase (IC50=168 nM) through the targeting of Met282 of AKT (Met173 of PKA-AKT chimera), as well as 20-fold selectivity over p70S6K (IC50=120 nM). CCT128930 hydrochloride induces cell cycle arrest, DNA damage, and autophagy. Antitumor activity[1][2].
Hematein is a oxidation product of hematoxylin acted as a dye[1]. Hematein is an allosteric casein kinase II inhibitor with an IC50 of 0.74 μM. Hematein inhibits Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increases apoptosis in lung cancer cells[2].
Coelonin is a dihydrophenanthrene with anti-inflammation activity. Coelonin inhibits LPS-induced PTEN phosphorylation. Coelonin inhibits NF-κB activation and p27Kip1 degradation by regulating the PI3K/AKT pathway negatively. Coelonin can inhibit IκBα phosphorylation and degradation and increases the expression of IκBα protein[1][2].
Licoricidin (LCD) is isolated from Glycyrrhiza uralensis Fisch, possesses anti-cancer activities.Licoricidin (LCD) inhibit SW480 cells (IC50=7.2 μM) by inducing cycle arrest, apoptosis and autophagy, and is a potential chemopreventive or chemotherapeutic agent against colorectal cancer[1].Licoricidin (LCD) inhibits Lung Metastasis by inhibition of tumor angiogenesis and lymphangiogenesis as well as changes in the local microenvironment of tumor tissues the anticarcinogenic effect[1].licoricidin enhanced gemcitabine-induced cytotoxicity in Osteosarcoma (OS) cells by inactivation of the Akt and NF-κB pathways in vitro and in vivo[3]. Licoricidin blocks UVA-induced photoaging via ROS scavenging, limits the activity of MMP-1, it can be considered as an active ingredient in new topically applied anti-ageing formulations[4].
MKC-1 (Ro-31-7453) is an orally active and potent cell cycle inhibitor with broad antitumor activity. MKC-1 inhibits the Akt/mTOR pathway. MKC-1 arrests cellular mitosis and induces cell apoptosis by binding to a number of different cellular proteins including tubulin and members of the importin β family[1][2][3].
PI3K/AKT-IN-2 (Compound 12c) is a PI3K and AKT inhibitor. PI3K/AKT-IN-2 blocks the epithelial-mesenchymal transition (EMT) and induces apoptosis. PI3K/AKT-IN-2 inhibits the polymerization of tubulin[1].
SY-LB-35 is a potent bone morphogenetic protein (BMP) receptor agonist. SY-LB-35 can stimulate significant increases in cell number and cell viability in the C2C12 myoblast cell line, and causes shifts towards the S and G2/M phases of the cell cycle. SY-LB-35 stimulates canonical Smad and non-canonical PI3K/Akt, ERK, p38 and JNK intracellular signaling pathways[1].
Yuanhuadin, extracted from Genkwa Flos Daphne genkwa, has antitumor activity through inhibiting Akt/mTOR and EGFR pathways, induce cell-cycle arrest and abortion[1].
TD52, an Erlotinib (HY-50896) derivative, is an orally active, potent cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibitor. TD52 mediates the apoptotic effect in triple-negative breast cancer (TNBC) cells via regulating the CIP2A/PP2A/p-Akt signalling pathway. TD52 indirectly reduced CIP2A by disturbing Elk1 binding to the CIP2A promoter. TD52 has less p-EGFR inhibition and has potent anti-cancer activity[1].
PI3Kδ-IN-10 is a highly potent and orally active PI3Kδ inhibitor with IC50 of 2 nM. PI3Kδ-IN-10 robustly suppresses the downstream AKT pathway to induce subsequent apoptosis in hepatocellular carcinoma models[1].
Cenisertib (AS-703569) is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5 and FLT3. Cenisertib induces major growth-inhibitory effects by blocking the activity of several different molecular targets in neoplastic mast cells (MC)[1]. Cenisertib inhibits tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia[2].
PI3K/Akt/CREB activator 1 (compound AE-18) is a potent, orally active PI3K/Akt/CREB activator. PI3K/Akt/CREB activator 1 promotes neuronal proliferation, induced differentiation of Neuro-2a cells into a neuron-like morphology, and accelerated the establishment of axon-dendrite polarization of primary hippocampal neurons through upregulating brain-derived neurotrophic factor via the PI3K/Akt/CREB pathway. PI3K/Akt/CREB activator 1 can be used in research of vascular dementia (VaD)[1].
PI3K/Akt/mTOR-IN-2 is a PI3K/AKT/mTOR pathway inhibitor. PI3K/Akt/mTOR-IN-2 possess anti-cancer effects and selectivity against MDA-MB-231 cells with IC50 value of 2.29 μM. PI3K/Akt/mTOR-IN-2 can induce cancer cell cycle arrest and apoptosis[1].
Rotundic acid, a triterpenoid obtained from I. rotunda, induces DNA damage and cell apoptosis in hepatocellular carcinoma through AKT/mTOR and MAPK Pathways. Rotundic acid possesses anti-inflammatory and cardio-protective abilities[1].