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].
6-O-Isobutyrylbritannilactone is a natural melanogenesis inhibitor. 6-O-Isobutyrylbritannilactone, a sesquiterpene, can be isolated from the flowers of Inula britannica. 6-O-Isobutyrylbritannilactone inhibits IBMX (HY-12318)-induced melanin production in B16F10 cells. 6-O-Isobutyrylbritannilactone also regulates ERK, PI3K/AKT, and CREB, shows antimelanogenic activity in zebrafish embryos models[1].
AKT-IN-12 (compound 3e) is a potent Akt kinase inhibitor with an IC50 value of 0.55 μM. AKT-IN-12 induces G0/G1 cell cycle arrest and apoptosis. AKT-IN-12 also inhibits p-AKT, p-ERK, and activates p-JNK, JNK. AKT-IN-12 can be used for researching leukemia[1].
3,4,5-Tricaffeoylquinic acid is isolated from barks of Ilex rotunda Thunb, used in the research of the pro-inflammatory mediator-induced skin disease[1].
Niloticin, tetracyclic triterpenoid compound, is a osteoclastogenesis inhibitor. Niloticin shows anti-viral, antioxidative, and mosquitocidal activities. Niloticin inhibits osteoclastogenesis by blocking RANKL-RANK interaction and suppressing the AKT, MAPK, and NF-κB signaling pathways[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].
Musk ketone (MK) is a widely used artificial fragrance. Musk ketone shows mutagenic and comutagenic effects in Hep G2 cells and induces neural stem cell proliferation and differentiation in cerebral ischemia via activation of the PI3K/Akt signaling pathway. In the brain, musk ketone is neuroprotective against stroke injury through inhibition of cell apoptosis[1][2][3].
Adropin (34-76) (human, mouse, rat) regulates fuel selection preferences in skeletal muscle. Adropin increases insulin-induced Akt phosphorylation and cell-surface expression of GLUT4, in diet-induced obesity (DIO) mouse.
Honokiol is a bioactive, biphenolic phytochemical that possesses potent antioxidative, anti-inflammatory, antiangiogenic, and anticancer activities by targeting a variety of signaling molecules. It inhibits the activation of Akt and enhances the phosphorylation of ERK1/ERK2.
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].
Communic acid ((+)-Communic acid) is a natural compound isolated from the branches of Platycladus orientalis. Communic acid displays minimum inhibitory concentration of 31 μM and IC50 of 15 μM against M. tuberculosis H37Ra.Communic acid exhibits protective effects against UVB-induced skin aging[1][2][3].
Phellodendrine, a isoquinoline alkaloid, is one of important characteristic ingredients in the Phellodendri chinensis cortex. phellodendrine is against AAPH-induced oxidative stress through regulating the AKT/NF-κB pathway. Phellodendrine has good antioxidant, and anti-inflammatory effect [1].
Actein is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida. Actein suppresses cell proliferation, induces autophagy and apoptosis through promoting ROS/JNK activation, and blunting AKT pathway in human bladder cancer. Actein has little toxicity in vivo[1][2].
Deferoxamine (Deferoxamine B) is an iron chelator (binds to Fe(III) and many other metal cations), is widely used to reduce iron accumulation and deposition in tissues. Deferoxamine upregulates HIF-1α levels with good antioxidant activity. Deferoxamine also shows anti-proliferative activity, can induce apoptosis and autophagy in cancer cells. Deferoxamine can be used in studies of diabetes, neurodegenerative diseases as well as anti-cancer and anti-COVID-19[1][2][3][4][5].
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].
MS5033 is a potent PROTAC-based AKT (protein kinase B) degrader, with a DC50 of 430 nM in PC3 cells[1].
IBL-302 (AMU302) is an orally available dual-signaling inhibitor of PIM and PI3K/AKT/mTOR with activity against breast cancer and neuroblastoma. IBL-302 demonstrated in vivo efficacy in a nude mouse xenograft model, inhibiting trastuzumab (HY-P9907) resistance challenges. IBL-302 also enhances the effects of common cytotoxic chemotherapy drugs cisplatin (HY-17394), doxorubicin (HY-15142A), and etoposide (HY-13629)[1][2][3].