MK-2206 is an orally active, highly potent and selective allosteric Akt inhibitor, with IC50s of 8, 12, and 65 nM for Akt1, Akt2, and Akt3, respectively. Many breast cancer cell lines, and PIK3CA-mutant and cell lines with PTEN loss are sensitive to MK-2206. Anticancer activities[1][2].
2-Chlorophenoxazine is a Akt inhibitor with an IC50 value of 2-5 μM for in vitro. 2-Chlorophenoxazine can induce apoptosis.2-Chlorophenoxazine can be used for cancer diseases research[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].
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].
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].
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].
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].
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].
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].
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].
AKT-IN-2 is a potent, selective and orally bioavailable AKT inhibitor with an IC50 of 5 nM for AKT1[1].
MMP-9-IN-5 is a MMP-9 inhibitor (IC50: 4.49 nM) that forms hydrogen bond with MMP-9. MMP-9-IN-5 also inhibits AKT activity (IC50: 1.34 nM). MMP-9-IN-5 shows cell cytotoxicity and induces cell apoptosis. MMP-9-IN-5 can be used in the research of cancers[1].
MS170 is a potent and selective PROTAC AKT degrader. MS170 depletes cellular total AKT (T-AKT) with the DC50 value of 32 nM. MS170 binds to AKT1, AKT2, and AKT3 with Kds of 1.3 nM, 77 nM, and 6.5 nM, respectively[1].
Sophocarpine is one of the significant alkaloid extracted from the traditional herb medicine Sophora flavescens which has many pharmacological properties such as anti-virus, anti-tumor, anti-inflammatory. Sophocarpine significantly inhibits the growth of gastric cancer (GC) cells through multiple mechanisms such as induction of autophagy, activation of cell apoptosis and down-regulation of cell survival PI3K/AKT signaling pathway. Sophocarpine has been demonstrated to have anti-tumor activity in various cancer cells, including hepatocellular carcinoma, prostate cancer and colorectal cancer[1].
SB 203580 hydrochloride is a widely used p38 MAPK inhibitor with an IC50 of 0.3-0.5 μM. It shows more than 100-fold selectivity over PKB, LCK, and GSK-3β.
AKTide-2T is an excellent in vitro substrate for AKT and shows competitive inhibition of histone H2B phosphorylation with a Ki of 12 nM. AKTide-2T mimics the optimal phosphorylation sequence of Akt and is an inhibitory peptide with the wildtype AKTide lacking Thr in the S22 position[1].
Kihadanin B is a citrus limonoid that can be purified from the peels of immature Citrus unshiu. Kihadanin B suppresses adipogenesis through repression of the Akt-FOXO1-PPARγ axis in 3T3-L1 adipocytes[1].
FPA-124, a cell-permeable copper complex, is a selective Akt inhibitor with an IC50 of 0.1 μM. FPA-124 interacts with both the pleckstrin homology (PH) and the kinase domains of Akt. FPA-124 induces apoptosis[1][2].
MPT0E028 is an orally active and selective HDAC inhibitor with IC50s of 53.0 nM, 106.2 nM, 29.5 nM for HDAC1, HDAC2 and HDAC6, respectively[1]. MPT0E028 reduces the viability of B-cell lymphomas by inducing apoptosis and possesses potent direct Akt targeting ability and reduces Akt phosphorylation in B-cell lymphoma. MPT0E028 has good anticancer activity[2].
Perifosine is an oral Akt inhibitor. All cells are sensitive to the antiproliferative properties of Perifosine with an IC50 of ~0.6-8.9 μM.
MK 2206 is an orally active allosteric Akt inhibitor with IC50s of 5, 12 and 65 nM for Akt1, Akt2 and Akt3, respectively.
Kazinol B, a prenylated flavan with a dimethyl pyrane ring, is an inhibitor of nitric oxide (NO) production. Kazinol B improves insulin sensitivity by enhancing glucose uptake via the insulin-Akt signaling pathway and AMPK activation. Kazinol B has the potential for diabetes mellitus research[1][2].
MS143 is a potent AKT degrader (DC50=46 nM and GI50=0.8 µM in PC3 cells). MS143 induces rapid and robust AKT degradation in a concentration- and time-dependent manner via hijacking the ubiquitin-proteasome system. MS143 can suppress cancer cell growth[1].
SC79 is a selective and cell-permeable Akt activator which activates Akt phosphorylation and inhibits Akt membrane translocation.
CAY10404 is a potent and highly selective cyclooxygenase-2 (COX-2) inhibitor with an IC50 of 1 nM. CAY10404 exhibits no inhibition of COX-1 (IC50>500 µM)[1]. CAY10404 is a potent inhibitor of PKB/Akt and MAPK signaling pathways and induces apoptosis in NSCLC cells. CAY10404, a diarylisoxazole, has good analgesic, anti-inflammatory, and anti-cancer activities[2][3].
MMP-9-IN-3 is a MMP-9 inhibitor (IC50: 5.56 nM) that forms hydrogen bond with MMP-9. MMP-9-IN-3 also inhibits AKT activity (IC50: 2.11 nM). MMP-9-IN-3 shows cell cytotoxicity and induces cell apoptosis. MMP-9-IN-3 can be used in the research of cancers[1].
AKT-I-1 is a selective inhibitor of Akt1, with an IC50 of 4.6 µM[1].
AKT inhibitor VIII is a cell-permeable quinoxaline compound that has been shown to potently, selectively, allosterically, and reversibly inhibit Akt1, Akt2, and Akt3 activity with IC50s of 58 nM, 210 nM, and 2119 nM, respectively.