Akt Inhibitor

Y-27632 is a ROCK inhibitor with K_i values of 220 nM and 300 nM for ROCK1 and ROCK2, respectively. Y-27632 exerts anti-inflammatory and immunomodulatory effects in systemic lupus erythematosus models by inhibiting the ROCK/NF-κB pathway. Y-27632 enhances autophagy by inhibiting the AKT/mTOR pathway, thereby inducing apoptosis apoptosis in oral squamous cell carcinoma. Y-27632 induces the formation of tunneling nanotubes in ARPE-19 cells and significantly enhances mitochondrial transfer through these channels. Y-27632 promotes neurite outgrowth in PC12 cells by activating the Rac1/NOX1/ROS/AKT/PAK1 signaling cascade.

MK-2206 dihydrochloride (MK-2206 2HCl) is an orally active pan-AKT inhibitor, with IC₅₀ values of 8 nM, 12 nM and 65 nM against AKT1, AKT2 and AKT3, respectively. MK-2206 dihydrochloride inhibits the Akt/mTOR signaling pathway and reduces the levels of downstream GSK3β and Mcl-1 via proteasomal degradation. MK-2206 dihydrochloride induces G1-phase cell cycle arrest, apoptosis, epithelial-mesenchymal transition, fibroblast activation and extracellular matrix deposition. MK-2206 dihydrochloride causes transient hyperglycemia and hyperinsulinemia in animals. MK-2206 dihydrochloride can be used in research related to solid tumors, renal fibrosis and hypercholesterolemia.

Leupeptin hemisulfate is a broad-spectrum protease inhibitor. By inhibiting the activation of the PTEN/PI3K/Akt/NF-κB/ERK1/2/p38 signaling pathway, Leupeptin hemisulfate significantly reduces LPS-induced NO and ROS production, mitochondrial membrane potential hyperpolarization, phagocytic activity, pro-inflammatory cytokine release, and M1 polarization in mouse peritoneal macrophages, and reverses autophagic flux impairment. It also decreases Concanavalin A (HY-P2149)-induced proliferation index of mouse splenic lymphocytes and the Th1/IL-10 and Th2/IL-10 cytokine ratios, thereby modulating innate and adaptive immune responses. Leupeptin hemisulfate inhibits blood coagulation and tumorigenesis in mouse skin. Leupeptin hemisulfate can be used in research on chronic inflammatory diseases and skin tumorigenesis.

CX-5461 is a selective, orally active RNA polymerase I inhibitor. CX-5461 disrupts the formation of the SL1-rDNA complex, thereby blocking the transcription initiation of ribosomal RNA without altering the activity of RNA polymerase II, DNA replication, or protein translation processes. CX-5461 upregulates the expression of p21, MDM2, Sestrin1/2, and phosphorylated AMPKα, and reduces the level of phosphorylated Akt. CX-5461 induces G2/G2/M cell cycle arrest, Autophagy, Apoptosis, and cellular senescence, and activates CHK1, CHK2, and RPA. CX-5461 can be used in research related to osteosarcoma, cervical cancer, hematologic malignancies, high-grade serous ovarian cancer, and solid tumors.

Capivasertib (AZD5363) is an orally active and potent pan-AKT kinase inhibitor with IC₅₀ of 3, 7 and 7 nM for Akt1,Akt2 and Akt3, respectively.

Afatinib (BIBW 2992) is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC₅₀ values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFR^wt, EGFR^L858R, EGFR^L858R/T790M and HER2, respectively. Afatinib can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer.

Cilengitide (EMD 121974) is an integrin (integrin) inhibitor with blood-brain barrier permeability, with IC₅₀ values against human targets as follows: 0.61 nM for αvβ3, 8.4 nM for αvβ5, 14.9 nM for α5β1, 5400 nM for αIIbβ3, 2050 nM for αvβ6, 2350 nM for αvβ8. Cilengitide inhibits the binding of integrins to vitronectin, fibronectin, fibrinogen and LAP (TGF-β), and serves as an internal standard for solid-phase integrin binding assays. Cilengitide inhibits tumor cell viability, induces apoptosis, reduces the phosphorylation levels of STAT3, AKT and mTOR, downregulates the expression of PD-L1, inhibits cell viability and angiogenesis, regulates anti-tumor immune responses and slows tumor growth. Cilengitide can be used in research related to glioblastoma, melanoma, advanced solid tumors and refractory brain tumors.

α-Linolenic acid (ALA (free base); C18:3 (9Z,12Z,15Z) (free base); C18:3 n-3 (free base)) is an essential fatty acid that cannot be synthesized by humans. α-Linolenic acid can affect the process of thrombotic through the modulation of PI3K/Akt signaling. α-Linolenic acid possess the anti-arrhythmic properties and is related to cardiovascular disease and cancer.

Sapanisertib (INK-128; MLN0128; TAK-228) is an orally active dual mTORC1/mTORC2 inhibitor. Sapanisertib directly and simultaneously inhibits mTORC1/2 activity through competitive binding with ATP, thereby comprehensively blocking downstream processes such as protein and lipid synthesis and cytoskeletal reorganization, consequently suppressing tumor cell proliferation and promoting apoptosis. Sapanisertib is applicable to research on melanoma, ovarian cancer, pulmonary fibrosis, and hematological malignancies.

Ergothioneine is an imidazole-2-thione derivative with orally active histidine betaine. Ergothioneine is a specific inhibitor of p38-MAPK and Akt, which plays a protective role in cell apoptosis induced by stress. Ergothioneine has antioxidant activity.

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. Honokiol can readily cross the blood brain barrier.

Ipatasertib (GDC-0068) is an orally active, highly selective and ATP-competitive pan-Akt inhibitor with IC₅₀ values of 5, 18, 8 nM for Akt1/2/3, respectively. Ipatasertib synchronously activates FoxO3a and NF-κB through inhibition of Akt leading to p53-independent activation of PUMA. Ipatasertib also induces apoptosis in cancer cells and inhibits tumor growth in xenograft mouse models.

Oridonin (NSC-250682), a diterpenoid isolated from Rabdosia rubescens, acts as an inhibitor of AKT, with IC₅₀s of 8.4 and 8.9 μM for AKT1 and AKT2; Oridonin possesses anti-tumor, anti-bacterial and anti-inflammatory effects.

AKT inhibitor VIII (AKTi-1/2) 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.

Artemisinin (Qinghaosu), a sesquiterpene lactone, is an anti-malarial agent isolated from the aerial parts of Artemisia annua L. plants. Artemisinin inhibits AKT signaling pathway by decreasing pAKT in a dose-dependent manner. Artemisinin reduces cancer cell proliferation, migration, invasion, tumorigenesis and metastasis and has neuroprotective effects.

Olitigaltin (TD139) is a high-affinity Galectin-3 inhibitor with a K_d value of 14 nM. Olitigaltin inhibits the activity of the AKT/β-catenin pathway, induces Apoptosis, and downregulates SREBP1 expression. Olitigaltin enhances the phosphorylation level of ERK. Olitigaltin alleviates bleomycin (HY-17565A)-induced advanced pulmonary fibrosis in mice. Olitigaltin delays the onset of diabetes, and improves glucose tolerance and serum insulin levels. Olitigaltin alleviates liver injury. Olitigaltin maintains the structure of hippocampal excitatory synapses, restores γ-wave power in the hippocampal CA1 region, inhibits hippocampal neuroinflammation, and improves cognitive function in neuroinflammation models. Olitigaltin can be used in research related to thyroid cancer, idiopathic pulmonary fibrosis, type 1 diabetes, hepatitis, and cognitive dysfunction induced by neuroinflammation.

Scutellarin, an active flavone isolated from Scutellaria baicalensis, can down-regulates the STAT3/Girdin/Akt signaling in HCC cells, and inhibits RANKL-mediated MAPK and NF-κB signaling pathway in osteoclasts. Scutellarin is active against HIV-1IIIB, HIV-1(74V) and HIV-1KM018 with EC₅₀s of 26 μM, 253 μM and 136 μM, respectively.

Isoginkgetin is a pre-mRNA splicing inhibitor inhibitor. Isoginkgetin also inhibits activities of both Akt, NF-κB and MMP-9. Isoginkgetin inhibits the activity of the 20S proteasome, induces apoptosis and activates autophagy.

ML-7 hydrochloride is a selective and highly specific myosin light chain kinase (MLCK) inhibitor that acts as a trabecular meshwork (TM) relaxant. ML-7 hydrochloride enhances Quinocetone (HY-123581)-induced phosphorylation of ERK, p38 MAPK and JNK, attenuates Akt activation, and promotes apoptosis of hepatocellular carcinoma cells. ML-7 hydrochloride reduces Th2 cytokine secretion by inhibiting MLCK, while alleviating smooth muscle hyperplasia and collagen deposition. As a non-antibiotic adjuvant, ML-7 hydrochloride restores the sensitivity of drug-resistant bacteria to Tigecycline (HY-B0117). ML-7 hydrochloride can be used in research related to glaucoma, hepatocellular carcinoma, asthma, and Klebsiella pneumoniae infection.

Patritumab (Human Anti-ERBB3 Recombinant Antibody) is a neutralizing monoclonal antibody to ERBB3. Patritumab shows a synergy with Cetuximab (HY-P9905), potently inhibits the phosphorylation of EGFR, HER2, HER3, ERK, and AKT. Patritumab also induces cell apoptosis and suppresses the growth of pancreatic, non-small cell lung cancer, and colorectal cancer xenograft tumors.