AKT IN 1

AKT-IN-1 (AZD-26) is an allosteric AKT inhibitor (IC50: 1.04 μM).

ALK/PI3K/AKT-IN-1 (Compound 45) effectively inhibits the proliferation of cancer cell lines A549, H1975, and PC9, with IC50 values of 0.44, 0.83, and 1.51 μM, respectively. This compound enhances the expression of p21 and p27, and decreases the activity of CDK2 and p-Rb, causing cell cycle arrest at the G1 phase. It suppresses the ALK/PI3K/AKT signaling pathway, promotes mitochondrial membrane potential depolarization, and induces apoptosis in A549 cells. Furthermore, ALK/PI3K/AKT-IN-1 inhibits the formation and growth of A549 cell spheres.

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.

APN/AKT-IN-1 is a potent dual inhibitor of aminopeptidase N (APN) and protein kinase B (AKT), with IC50 values of 0.21 μM for APN and 0.27 μM for AKT inhibition. The compound effectively suppresses the phosphorylation of glycogen synthase kinase 3 beta (GSK3β), an intracellular substrate of AKT [1].

Akt/NF-κB/JNK-IN-1 (Compound 2i) is an inhibitor of the Akt, NF-κB, and JNK signaling pathways, demonstrating inhibition of nitric oxide production (IC50: 3.15 μM) and exhibiting anti-inflammatory effects.

PI3K/AKT-IN-1 is a dual PI3K and AKT inhibitor with anti-cancer activity. It inhibits PI3Kγ, PI3Kδ, and AKT, suppressing the PI3K/AKT pathway and inducing caspase 3-dependent apoptosis, suitable for cancer research.

Akt NF-κB MAPK-IN-1 (compound 2m) is a potent, orally active inhibitor of NO with an IC50 of 7.70 μM and low toxicity, exhibiting anti-inflammatory effects by blocking the Akt NF-κB and MAPK signaling pathways [1].

Akt/ROCK-IN-1 (B12) is a dual inhibitor of Akt and ROCK with IC50 values of 0.023 nM and 1.47 nM, respectively, and demonstrates antitumor efficacy against neuroblastoma [1].

EGFR Akt-IN-1 (compound 17) serves as an effective inhibitor of EGFR Akt, exhibiting IC50 values of 12.89 μM and 10.88 μM in A549 cells, respectively. This compound induces cell cycle arrest at the S phase.

VEGFR-2 AKT-IN-1 (compound 17) is a dual inhibitor of VEGFR-2 and AKT with IC50 values of 0.164 μM and 0.452 μM, respectively. It exhibits antitumor activity.

Akt mTOR-IN-1 (Compound 8r) is an inhibitor of the AKT mTOR signaling pathway, exhibiting an IC50 of 0.8 µM and possessing anticancer activity. This compound decreases the expression of Caspase 3 while enhancing the expression of the autophagic protein Cyclin B1, thereby inducing autophagy and apoptosis. Akt mTOR-IN-1 is applicable for research in the field of non-small cell lung cancer (NSCLC).

Caffeic Acid Phenethyl Ester (Phenylethyl Caffeate) (CAPE) inhibits the activation of nuclear transcription factor NF-kappa B and may suppress p70S6K and Akt-driven signaling pathways, with antineoplastic, cytoprotective and immunomodulating activities. CAPE is the phenethyl alcohol ester of caffeic acid and a bioactive component of honeybee hive propolis. In addition, CAPE inhibits PDGF-induced proliferation of vascular smooth muscle cells through the activation of p38 mitogen-activated protein kinase (MAPK) and hypoxia-inducible factor (HIF)-1alpha and subsequent induction of heme oxygenase-1 (HO-1).

5,6-Benzoflavone (β-Naphthoflavone) is an exogenous ligand for the aryl hydrocarbon receptor, which disrupts zinc homeostasis in human hepatocellular carcinoma HepG2 cells. 5,6-Benzoflavone (β-Naphthoflavone) possesses anti-inflammatory and antioxidant activities, inhibits LPS-induced inflammation through the AKT/Nrf-2/HO-1-NF-kappaB signaling axis, inhibits TNF-α-induced ICAM-1 and VCAM-1 expression, which can be used to study neurodegenerative diseases.

iHCK-37 (ASN05260065) is a selective Hck inhibitor with antitumor activity, blocking HIV-1 viral replication. iHCK-37 reduces PI3K/AKT and MAPK/ERK pathway activation after erythropoietin induction in high Hck-expressing cells, useful in chronic myelogenous leukemia (CML) research.

ZINC00784494 is a selective inhibitor of LCN2 (lipocalin-2), which inhibits cancer cell proliferation and reduces AKT phosphorylation levels, prevents the transition of the cell cycle from the G0 G1 phase to the S phase, and promotes apoptosis. It can be used for the study of inflammatory breast cancer (IBC).

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.

API-1 (NSC-177223) is a potent inhibitor of Akt. It induces GSK3-dependent, β-TrCP- and FBXW7-mediated Mcl-1 degradation, resulting in induction of apoptosis .

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.

Akt1 and Akt2-IN-1 is an allosteric inhibitor of Akt1 (IC50=3.5 nM) and Akt2 (IC50=42 nM). It has potent and balanced activity.

AMG 511 is a potent and orally available pan inhibitor of class I PI3Ks (Kis of 4 nM, 6 nM, 2 nM, and 1 nM for PI3Kα, β, δ, and γ, respectively), exhibiting anti-tumor activity in a mouse glioblastoma xenograft model[1]. AMG 511 significantly suppresses PI3K signaling as indicated by a decrease in p-Akt (Ser473).

9-Decyn-1-ol is an alkyl/ether-based PROTAC linker used in synthesizing PROTACs, acting as a conjugation agent to combine GDC-0068 and Lenalidomide to form INY-03-041. INY-03-041 is a potent and highly selective pan-Akt degrader that inhibits Akt1, Akt2, and Akt3 with IC50 values of 2.0 nM, 6.8 nM, and 3.5 nM, respectively[1].

Ipatasertib-NH2 (GDC-0068-NH2;RG7440-NH2) is a ligand for the target protein AKT used in PROTAC, binding to lenalidomide, a ligand of ubiquitin E3 ligase cereblon (CRBN), via a ten-hydrocarbon linker to form INY-03-041 for AKT degradation[1].

Lenalidomide-C9-aldehyde is a synthesized E3 ligase ligand-linker conjugate that incorporates the Lenalidomide based cereblon ligand and a linker. Lenalidomide-C9-aldehyde can be used in the synthesis of a series of PROTACs, such as INY-03-041. INY-03-041

PI3K-IN-1 (Voxtalisib Analogue) is a dual inhibitor of mTOR/PI3K, mostly for p110γ , also inhibits DNA-PK and mTOR.