Dipentyl phthalate is an endocrine-disrupting phthalate plasticizer. Dipentyl phthalate increases AMPK phosphorylation and decreases AKT1 phosphorylation and SIRT1 levels. Dipentyl phthalate reduces adrenocorticotropic hormone levels. Dipentyl phthalate is a testicular toxicant[1].
Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. Cyclovirobuxine D induces autophagy and attenuates the phosphorylation of Akt and mTOR[1]. Cyclovirobuxine D inhibits cell proliferation of gastric cancer cells through suppression of cell cycle progression and inducement of mitochondria-mediated apoptosis[2]. Cyclovirobuxine D is beneficial for heart failure induced by myocardial infarction[3].
Chromeceptin is an IGF signaling pathway inhibitor. Chromeceptin suppresses IGF2 at mRNA and protein levels in hepatocyte and HCC cells. Chromeceptin inhibits the Phosphorylation levels of AKT and mTOR[1].
N-Oleoyl glycine is a lipoamino acid, which stimulates adipogenesis associated with activation of CB1 receptor and Akt signaling pathway in 3T3-L1 adipocyte.
Acetyl-Exenatideyes is an acetylated derivative of Exenatide. Exenatide has the function similar to insulin, which can be used for research of type 2 diabetes. Exenatide can promote Th17 differentiation, inhibits Tregs differentiation, downregulates PI3K/Akt/FoxO1 phosphorylation[1].
24-Methylenecycloartanyl ferulate is a γ-oryzanol compound. 24-Methylenecycloartanyl ferulate promotes parvin-beta expression in human breast cancer cells. 24-Methylenecycloartanyl ferulate is a potential ATP-competitive Akt1 inhibitor (EC50= 33.3μM)[1].
Akt3 degrader 1 (compound 12l) is a selective Akt3 degrader that overcomes Osimertinib (HY-15772)-induced resistance in H1975OR NSCLC cells. Akt3 degrader 1 also has anti-proliferative activity and significantly inhibits tumour growth in mice. Akt3 degrader 1 can be used in the study of drug-resistant non-small cell lung cancer[1].
Isoprocurcumenol is a guaiane type sesquiterpene, that can be isolated from Curcuma comosa. Isoprocurcumenol can activate EGFR signaling. Isoprocurcumenol increases the phosphorylation of ERK and Akt. Isoprocurcumenol promotes the proliferation of keratinocytes[1][2][3].
Apoptin-derived peptide is an antitumor polypeptide with cytotoxicity. Apoptin-derived peptide promotes apoptosis and necrosis of gastric cancer (GC) cells by regulating PI3K/AKT/ARNT signaling. Apoptin-derived peptide inhibited the invasion and migration of cancer cells, and inhibited the expression and phosphorylation of the subunit p85 of PI3K, which further inhibited the PI3K/AKT pathway involved in the development of gastric cancer[1].
Sennidin A, isolated from the leaves of Cassia angustifolia, inhibits HCV NS3 helicase, with an IC50 of 0.8 μM. Sennidin A induces phosphorylation of Akt and glucose transporter 4 (GLUT4) translocation. Sennidin A stimulates the glucose incorporation[1][2].
AKT-IN-13 (compound 4b) is a potent Akt inhibitor with IC50s of 1.6 nM, 2.4 nM and 0.3 nM for Akt1, Akt2 and Akt3, respectively. AKT-IN-13 can be used for researching anticancer[1].
Recilisib sodium (ON 01210) is a radioprotectant, which can activate AKT, PI3K activities in cells[1].
API-1, a potent Akt/PKB inhibitor, binds to the PH domain and inhibits Akt membrane translocation. API-1 efficiently reduces the phosphorylation levels of Akt with an IC50 of ∼0.8 μM. API-1 is selective for PKB and does not inhibit the activation of PKC, and PKA. API-1 also induces apoptosis by synergizing with TNF-related apoptosis-inducing ligand (TRAIL)[1][2].
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].
DB07107 is a potent drug resistant T315I mutant Bcr-Abl tyrosine kinase inhibitor. DB07107 is also a potent Akt1 inhibitor with an IC50 value of 360 nM[1][2].
H-Ile-Lys-Val-Ala-Val-OH is one of the most potent active sites of laminin-1. H-Ile-Lys-Val-Ala-Val-OH promotes cell adhesion, neurite outgrowth, and tumor growth. H-Ile-Lys-Val-Ala-Val-OH stimulates BMMSC population growth and proliferation by activating MAPK/ERK1/2 and PI3K/Akt signalling pathways[1][2].
AKT-IN-14 (Example 2) free baseis 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 free basecan be used in cancer research[1].
(E/Z)-Afatinib ((E/Z)-BIBW 2992) is the mixture of (E)-Afatinib and (Z)-Afatinib. Afatinib (HY-10261) is an irreversible inhibitor of EGFR, by irreversibly binding to their ATP binding site to block activation of EGFR, HER2, HER4, and EGFRvIII. Afatinib used in co-administration with Temozolomide (HY-17364), potently targeting to EGFRvIII-cMet signaling in glioblastoma cells[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].
Eudebeiolide B is a compound that can be isolated from Salvia plebeia R. Br. Eudebeiolide B inhibits osteoclastogenesis by regulating RANKL-induced NF-κB, c-Fos and calcium signaling. Eudebeiolide B can be used for osteoclast-related diseases research[1].
Larixol is an fMLP inhibitor and also inhibits Src kinase, ERK1/2, p38 and AKT phosphorylation signals in immune regulation. Larixol can interfere with the interaction between the βγ subunit of the fMLP receptor Gi protein and its downstream molecules, thereby inhibiting fMLP-induced respiratory burst. Larixol inhibits fMLP (0.1 μM)-induced superoxide anion production (IC50: 1.98 μM), cathepsin G release (IC50: 2.76 μM), and chemotaxis. Larixol improves neutrophil hyperactivation and reduces inflammation or tissue damage. A series of Larixol derivatives were found to have inhibitory effects on FSGS-related TRPC6 functional mutants[1][2].
Artemisiane E (Compound 8) is a potent PI3K/AKT pathway inhibitor with an IC50 of 8.9 μM[1].
NTQ1062 (compound 22b) is a potent and orally active Akt inhibitor with IC50s of 0.4 nM, 6.3 nM and 0.1 nM for Akt1, Akt2 and Akt3, respectively. NTQ1062 induces cell apoptosis and arrests the cell cycle at G0/G1 phase. NTQ1062 exhibits antiproliferation activity against various cancer cells. NTQ1062 exhibits potent antitumor efficacy in LNCap xenograft mouse model[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].