akt-in-3

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

Polyphyllin D induces apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C, and cleaved-caspase-3 levels. Polyphyllin D has an anti-angiogenic effect. Polyphyllin D has toxicity in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis. Polyphyllin D has strong anticancer activity, can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

4-Vinylcyclohexene Dioxide (VCD) is an industrial epoxy resin intermediate and metabolite that exhibits a highly selective destructive effect on oocytes in primordial and primary follicles; it is used as a key inducer for establishing animal models of premature ovarian failure and premenopause. 4-Vinylcyclohexene Dioxide exerts its ovarian toxicity by activating caspase-dependent apoptotic pathways and can induce apoptosis in ovarian granulosa cells by upregulating reactive oxygen species and activating the PI3K/Akt/mTOR signaling pathway. It is used in reproductive toxicology and endocrine regulation research.

The combination of Valproic acid with Coumarin-3-carboxylic acid (3-Carboxycoumarin) suppresses the proliferation and migration of lung cancer cells via EGFR/VEGFR2/c-Met-Akt-NF-κB signaling pathways; this combination may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of lung cancer.

ethyl 2-[3,5-bis(trifluoromethyl)phenyl]-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxylate is a synthetic compound belonging to the curcumin family. It is involved in the regulation of immune response and inflammation through inhibition of the NF-κB signaling pathway, in the regulation of antioxidant response through activation of the Nrf2 signaling pathway, and in the regulation of cell survival and proliferation through inhibition of the Akt signaling pathway.

CAY10404 (3-(4-METHYLSULPHONYLPHENYL)-4-PHENYL-5-T) is a potent and highly selective inhibitor of COX-2 and COX-1. It is also a potent inhibitor of PKB/Akt and MAPK signalling pathways and induces apoptosis in NSC-LC cells, with analgesic, anti-inflammatory and anti-cancer activities.

Fusaric acid is an orally active multi-target inhibitor capable of inhibiting fibrosis-related signaling pathways such as NF-κB, TGF-β1/SMADs, and PI3K/AKT/mTOR. It also inhibits dopamine β-hydroxylase and reduces endogenous levels of norepinephrine and epinephrine. Fusaric acid activates apoptosis-related proteases such as Caspase-3/7, Caspase-8, and Caspase-9, thereby inducing oxidative stress and apoptosis. It chelates divalent metal cations, damages mitochondrial membrane structure, and exerts effects in improving myocardial fibrosis and alleviating cardiac hypertrophy. Additionally, it is applicable in research on esophageal cancer, liver cancer, and other conditions.

PDK4-IN-1 hydrochloride, an anthraquinone derivative, is a potent and orally active inhibitor of pyruvate dehydrogenase kinase 4 (PDK4) with an IC50 value of 84 nM.

PS210 is a potent and selective activator of PDK1 (Kd: 3 μM), specifically targeting the PIF-binding pocket of PDK1 without affecting other protein kinases such as S6K, PKB/Akt, or GSK3. Its prodrug, PS423, serves as a substrate-selective inhibitor of PDK1 in cells, inhibiting the phosphorylation and activation of S6K.

VEGFR-2/AKT-IN-2 (Compound 5) is an inhibitor of VEGFR-2/AKT, with an IC50 of 0.061 μM for VEGFR in human liver cancer cells. It reduces total and phosphorylated AKT in cells, increases BAX and caspase-3 levels, and decreases Bcl-2, thereby inducing apoptosis. Additionally, VEGFR-2/AKT-IN-2 halts the cell cycle at the S phase and inhibits the growth of human liver cancer cells.

NF-κB-IN-19 (Compound 8) is an NF-κB inhibitor. It effectively induces DNA damage in tumor cells through the NF-κB signaling pathway and promotes the production of reactive oxygen species (ROS), as well as induces autophagy and apoptosis. Additionally, NF-κB-IN-19 inhibits levels of VEGF and HIF-1α, exerting antiproliferative effects in tumor cells through the PI3K/AKT and STAT-3 pathways. It is also effective in overcoming cisplatin resistance and exhibits antitumor activity.

Clifutinib (Compound 9e) is an orally active, selective inhibitor of FMS-like tyrosine kinase 3 (FLT3-ITD) with an IC50 of 15.1 nM. It inhibits FLT3-ITD kinase activity and blocks downstream signaling pathways, including RAS/MAPK, PI3K/AKT, and JAK/STAT5. Clifutinib induces apoptosis in FLT3-ITD mutated acute myeloid leukemia (AML) cells and is a potential candidate for research in relapsed/refractory FLT3-ITD positive AML.

PI3K-IN-56 (Compound 1) is an orally active, potent, and selective irreversible inhibitor of phosphoinositide 3-kinase (PI3K). It irreversibly blocks the production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) and the downstream AKT signaling pathway. PI3K-IN-56 holds promise for research in PI3Kα-driven cancers, such as breast and ovarian cancer.

BMX-IN-3 (B6a) is an irreversible and selective inhibitor of BMX with an IC50 value of 12 nM. It induces cell cycle arrest and apoptosis, triggers protective autophagy, and inhibits the BMX/AKT/mTOR pathway. BMX-IN-3 (B6a) is applicable for research in gastric cancer.

AKT-IN-27 (4a) is a potential anticancer drug that functions by selectively targeting Akt-driven signaling pathways. It induces apoptosis by activating caspase-3, causing G2/M phase cell cycle arrest, and disrupting mitochondrial membrane potential. AKT-IN-27 (4a) is applicable in research on triple-negative breast cancer (TNBC).

PI3K/HDAC-IN-4 (Compound 31f) is a dual inhibitor targeting PI3K and HDAC, with an IC50 of 0.2μM. It demonstrates high selectivity for HDAC1-3, with IC50 values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively. As a potent pan-PI3K inhibitor, PI3K/HDAC-IN-4 has IC50 values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. This compound effectively induces apoptosis in tumor cells by concurrently inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. It shows significant antiproliferative activity across various tumor cell lines, such as MV4-11, Jeko-1, HL60, and MCF-7, with IC50 values of 0.2, 0.9, 0.8, and 1.5 μM, respectively. PI3K/HDAC-IN-4 is applicable in the study of lymphoma and leukemia.

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.

STAT3/AKT-IN-1 is a dual inhibitor of the signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) signaling pathways, demonstrating anti-tumor activity and inducing apoptosis in SGC-7901 cells.

KDM5B-IN-4 (compound 11ad) is a novel inhibitor of lysine demethylase 5B (KDM5B), with an IC50 of 0.025 μM for KDM5B. It increases the levels of the substrate H3K4me1/2/3 in PC-3 cells by inhibiting KDM5B. Furthermore, KDM5B-IN-4 induces G2/M phase arrest in PC-3 cells and downregulates proteins in the PI3K/AKT signaling pathway. Additionally, KDM5B-IN-4 reduces tumor volume in mice with minimal organ toxicity.

TYM-3-98 is a novel, selective PI3Kδ inhibitor (IC50=7.1 nM). It induces apoptosis by blocking PI3K/AKT/mTOR signaling in B-cell lymphoma models.

PI3Kδ-IN-21 (Compound 31) is a selective inhibitor of phosphoinositide 3-kinase δ (PI3Kδ), with an IC50 of 13.6 nM. It impedes the proliferation and differentiation of T cells through the PI3K/AKT/mTOR signaling pathway. In rat models, PI3Kδ-IN-21 exhibits favorable pharmacokinetic properties and demonstrates activity in improving experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein (MOG) in EAE models.

7,4'-Dimethoxy-3-hydroxyflavone is an orally active PAR4 antagonist. This compound inhibits PAR4-mediated human platelet aggregation with an IC50 of 1.4 μM. It disrupts PAR4-mediated aggregation and related signaling pathways, including NF-κB, Ca2+/protein kinase C (PKC), Akt, ERK, and p38. In a streptozotocin (STZ)-induced diabetic mouse model, 7,4'-Dimethoxy-3-hydroxyflavone inhibits vascular PAR4 expression, improves endothelial dysfunction, and reduces oxidative stress. Additionally, it prevents thrombosis in mice without affecting bleeding time.

ROR1-IN-3 (Compound 24d) is a potent and highly selective inhibitor of the ROR1 kinase, with an IC50 of 17.6 nM. It demonstrates significant antitumor activity and ROR1 inhibition both in vitro and in vivo, exhibiting strong antiproliferative effects. ROR1-IN-3 induces apoptosis in cancer cell lines and inhibits downstream AKT/mTOR and NF-κB signaling pathways. This compound is applicable for antitumor research.

PDGFRA/CAIX/XII-IN-1 is a multi-target inhibitor targeting PDGFRA, CA IX and CA XII, with an IC50 of 20 nM against PDGFRA and Ki values of 93.3 nM and 80.0 nM against CA IX and CA XII respectively. It targets and binds to the ATP-binding pocket of PDGFRA, thereby blocking the activation of downstream signaling pathways such as STAT3, AKT and ERK1/2. It induces G0/G1 phase cell cycle arrest and initiates endogenous apoptotic procedures, manifested as cleavage and activation of PARP-1, caspase-9 and caspase-3, upregulation of caspase 3/7 activity and inhibition of Mcl-1 protein expression. It exerts significant anti-proliferative effects in eosinophilic leukemia cells and can serve as a candidate tool compound for mechanism and efficacy research of leukemia.