PI3K/Akt/mTOR

HS-173, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor, has anti-tumor activity through promoting apoptosis and inhibiting angiogenesis.

BLY719 is an orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity.

CHIR99021 is an aminopyrimidine derivative that inhibits GSK3α and GSK3β with IC50 values of 10 and 6.7 nM, respectively.

SL 0101-1 is a selective inhibitor of p90 ribosomal S6 kinase (RSK) (IC50 = 89 nM for RSK2). It also inhibits the growth of MCF-7 human breast cancer cells with no effect on the normal breast cell line.

PIK-75 is an imidazopyridine that selectively inhibits p110α with an IC50 value of 5.8 nM.2 It inhibits p110γ and p110β considerably less effectively with IC50 values of 0.076 μM and 1.3 μM, respectively.

ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms.

PI-3065 is a small molecule and selective inhibitor of p110δ kinase with an Ki value of 1.5nM and IC50 value of 5nM

Acadesine is a selective activator of AMPK in both hepatocytes and adipocytes.

GSK2636771 is a potent, orally bioavailable, PI3K beta-selective inhibitor.

Rapamycin (Sirolimus) prevents activation of T cells and B-cells by inhibiting their response to interleukin-2 (IL-2).

AZD0156 is a potent and selective inhibitors of ATM kinase, with potential chemo-/radio-sensitizing and antineoplastic activities.

AZD1080 is a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans.

AZD2014 is an orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. mTOR kinase inhibitor.

Quercetin inhibits many enzyme systems including tyrosine protein kinase, phospholipase A2, phosphodiesterases, mitochondrial ATPase, PI 3-kinase and protein kinase C.

FK-506 is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection. It reduces interleukin-2 (IL-2) production by T-cells.

BAY 80-6946 is a phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity.

OSU-03012 is a novel celecoxib derivative, without cyclooxygenase-2 inhibitory activity, capable of inducing apoptosis in various cancer cells types.

Tideglusib is a GSK-3 inhibitor currently in phase II clinical trials for the treatment of Alzheimer disease and progressive supranuclear palsy

SF2523 is a highly selective and potent inhibitor of PI3K with IC50s of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.

Wortmannin is a potent, selective, cell-permeable and irreversible inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase) (IC50 = 2 - 4 nM) which also potently inhibits polo-like kinase 1 (PLK1) (IC50 = 5.8 nM).

MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM, respectively.

BML-275 is a cell-permeable pyrazolopyrimidine compound shown to be an AMP-activated protein kinase (AMPK) and fatty acid synthase inhibitor.

VE-821 is a potent and selective inhibitor of protein kinase ATR.

BI-D1870 is a potent and specific inhibitor of the p90 ribosomal S6 kinase (RSK) isoforms in vitro and in vivo, which inhibits RSK1, RSK2, RSK3 and RSK4 in vitro with an IC50 of 10?€?30 nM.

OTSSP167 is a highly potent MELK (maternal embryonic leucine zipper kinase) inhibitor with IC50 of 0.41 nM.

LY2090314 is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) which plays an important role in many pathways, including initiation of protein synthesis, cell proliferation, cell differentiation, and apoptosis.

XL147 is a potent, selective and orally bioavailable small molecule inhibitor of class I phosphatidylinositol 3 kinase (PI3K) with potential antineoplastic activity.

PF-04691502 is a PI3K/mTOR kinase inhibitor, is also an agent targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in the PI3K/mTOR signaling pathway.

Gedatolisib (PKI-587) is a highly potent PI3K/mTOR kinase inhibitor that inhibits PI3K-α,β,γ, δ isoforms and mTOR with IC50 of 0.4, 6.0, 5.4, 6.0 and 1.6 nM respectively.

Shikonin, a component of chinese herbal medicine, inhibits chemokine receptor function and suppresses human immunodeficiency virus type 1.

Samotolisib (LY3023414) is an oral ATP competitive inhibitor of the class I PI3K isoforms, mTOR and DNA-PK, extracted from patent WO/2012097039A1, compound example 1, has an IC50 of 64.9 nM, 42.1 nM, 10.6 nM, 19.1 nM for Akt1(pT308), Akt1 (pS473), P70S6(pT389), S6RP(pS240/242).

Sexangularetin 3-sophoroside is an activator of PDK1 and Akt phosphorylation pathways, demonstrating significant neuroprotective effects. This compound restores levels of phosphorylated GSK-3β protein and functions as a reactive oxygen species (ROS) inhibitor. Additionally, it modulates the expression of superoxide dismutase 1 and catalase mRNA, making it a valuable tool for research related to neurodegenerative conditions such as Parkinson’s disease.

RapaLink-1 is a third-generation bivalent inhibitor targeting the mechanistic target of rapamycin (mTOR). By combining Rapamycin with MLN0128 through an inert linker, RapaLink-1 demonstrates superior efficacy in inhibiting both wild-type and mutant forms of mTOR compared to other inhibitors. This compound effectively crosses the blood-brain barrier, promoting durable mTORC1 inhibition via FKBP12 binding. Additionally, RapaLink-1 exhibits anticancer properties and may play an antithrombotic role in antiphospholipid syndrome by enhancing autophagy.

mTOR inhibitor-8 is a potent inhibitor of the mechanistic target of rapamycin (mTOR), functioning through the interaction with FKBP12. This compound effectively suppresses mTOR activity and induces autophagy in A549 human lung cancer cells. It is a valuable tool for studying mTOR signaling pathways and the role of autophagy in cancer research.

Manzamine A hydrochloride is an orally active beta-carboline alkaloid that specifically inhibits GSK-3β and CDK-5, with IC50 values of 10.2 μM and 1.5 μM, respectively. This compound demonstrates significant antimalarial and anticancer properties, with additional effects such as inhibiting vacuolar ATPases and autophagy processes in pancreatic cancer cells. Furthermore, Manzamine A hydrochloride exhibits potent activity against HSV-1, making it valuable for various research applications in cancer biology and virology.

Zederone is a sesquiterpene that acts as an inhibitor of the mTOR/p70S6K signaling pathway. It effectively reduces ovarian cancer cell proliferation and exhibits selective inhibition of various CYP450 enzymes, notably with IC50 values of 2.9 μM for CYP2B6 and 9.2 μM for CYP2C9. Additionally, Zederone demonstrates antibacterial properties against multi-drug resistant strains of Staphylococcus aureus and has been shown to improve cognitive function while modulating gut bacterial dysbiosis. However, caution is warranted due to its hepatotoxicity, evidenced by an LD50 of approximately 223 mg/kg in mice.

Galegine hemisulfate is a guanidine derivative that functions as an AMPK activator. It has demonstrated potential in promoting weight loss in mice and effectively activates AMPK in 3T3-L1 adipocytes, L6 myotubes, H4IIE rat hepatoma, and HEK293 human kidney cell lines. Additionally, Galegine hemisulfate exhibits antibacterial properties, with a minimum inhibitory concentration of 4 mg/L against strains of Staphylococcus aureus, making it relevant for various biological research applications.

Galegine hydrochloride is an AMPK activator that influences energy metabolism and contributes to weight management. Derived from the guanidine structure, this compound has shown efficacy in activating AMPK in various cell lines, including 3T3-L1 adipocytes, L6 myotubes, H4IIE rat hepatoma, and HEK293 human kidney cells. Additionally, galegine hydrochloride exhibits antibacterial properties, demonstrating a minimum inhibitory concentration of 4 mg/L against Staphylococcus aureus strains, highlighting its potential in metabolic and antimicrobial research applications.

Foenumoside B is a triterpene saponin that activates AMP-activated protein kinase (AMPK) signaling. This compound inhibits PPARγ-induced adipogenesis and promotes lipid metabolism shift towards lipolysis. Foenumoside B is useful for investigating obesity and related metabolic disorders, making it a valuable tool for research in metabolic health.

PI3Kδ/BET-IN-1 is a selective inhibitor targeting both PI3Kδ and the bromodomain BRD4-BD1. With an IC50 of 112 nM for PI3Kδ and 19 nM for BRD4-BD1, this compound demonstrates potent antiproliferative effects in diffuse large B-cell lymphoma (DLBCL) cells. Its dual inhibition mechanism makes it a valuable tool for research into cancer biology and therapeutic development.

Indirubin-3′-oxime (IDR3O) is a synthetic derivative of indirubin that functions as a potent inhibitor of cyclin-dependent kinases (CDKs), glycogen synthase kinase 3β (GSK3β), and all three isoforms of c-Jun N-terminal kinases (JNK1, JNK2, JNK3). It demonstrates inhibitory activity with IC50 values of 0.8 μM, 1.4 μM, and 1.0 μM for each JNK isoform, respectively. Indirubin-3′-oxime is also known to promote chondrocyte height growth through the activation of Wnt/β-catenin signaling, making it relevant for studies in cellular growth and differentiation.

IMM-H007 is a potent AMPK (AMP-activated protein kinase) activator and TGFβ1 (transforming growth factor β1) antagonist. This compound exhibits cardioprotective effects by activating AMPK, which subsequently reduces endothelial inflammation through the inactivation of NF-κB and JNK/AP1 signaling pathways. Additionally, IMM-H007 regulates lipid metabolism, effectively resolving hepatic steatosis in high-fat diet-fed hamsters. It is suitable for research applications focused on nonalcoholic fatty liver disease (NAFLD) and inflammatory atherosclerosis.

JRN73958 is a potent inhibitor of the PI3K/Akt, MAPK, and NF-κB signaling pathways. This compound effectively reduces LPS/IFNγ-induced activation of these pathways, making it a valuable tool for investigating their roles in cancer biology, particularly in leukemia research. Additionally, JRN73958 acts as an Nrf2/ARE activator, further expanding its utility in studies related to oxidative stress and cell survival mechanisms.

N-Acetyldehydroanonaine is a natural alkaloid that functions as a ligand for AKT1 and MAPK1, key regulators in various signaling pathways. This compound, derived from plants of the Zanthoxylum genus, exhibits potential biological activity relevant to cancer research. Its application is particularly significant in the study of diseases such as gastric cancer, making it a valuable tool for investigators exploring therapeutic targets and mechanisms in oncogenesis.

ST-162 is a dual antagonist of the MAPK and PI3K signaling pathways. It demonstrates significant antitumor activity and has been shown to enhance the efficacy of immune checkpoint inhibitors. This compound is suitable for cancer research, particularly in the study of melanoma and other malignancies.

GSK-3β inhibitor 13 is a potent inhibitor of glycogen synthase kinase 3 beta (GSK-3β) and GSK-3α, demonstrating IC50 values of 0.73 nM and 0.35 nM respectively. This orally active compound exhibits blood-brain barrier permeability and effectively reduces tau phosphorylation, with an IC50 of 58 nM. Its ability to modulate tau phosphorylation makes it valuable for research focused on neurodegenerative disorders, particularly Alzheimer's disease, by potentially mitigating the formation of neurofibrillary tangles.

PI3K/PIKK-IN-1 is a potent inhibitor of phosphoinositide 3-kinases (PI3K) and PI3-kinase-related kinases (PIKK). This compound is utilized in the development of antibody-drug conjugates (ADCs), making it valuable for therapeutic applications. It is particularly relevant in the research of various cancers, including breast cancer, multiple myeloma, Burkitt lymphoma, diffuse large B-cell lymphoma, and non-small cell lung cancer, aiding in the exploration of targeted cancer therapies.

Akt/ROCK-IN-1 is a potent dual inhibitor targeting Akt and ROCK, exhibiting IC50 values of 0.023 nM and 1.47 nM, respectively. This compound demonstrates significant antitumor activity, particularly in neuroblastoma models. It serves as a valuable tool for research into cancer biology and therapeutic development.

PI3Kα-IN-16 is a selective PI3Kα inhibitor with an IC50 value of 4.28 μM. It effectively suppresses PI3K-mediated colorectal cancer growth and migration, demonstrating its potential as a therapeutic agent. Additionally, PI3Kα-IN-16 inhibits the Wnt signaling pathway, making it a valuable tool for research in cancer biology and signaling pathways.

AMPK Activator 18 is a potent allosteric activator of AMPK complexes, particularly those containing the β2 isoform. It effectively activates α2-containing AMPK α2β2γ1 and α2β2γ3 complexes, exhibiting EC50 values of 17.2 nM and 82.1 nM, respectively. This compound stimulates β2-AMPK in cellular contexts and enhances glucose uptake in isolated skeletal muscle. Additionally, AMPK Activator 18 promotes phosphorylation of acetyl-coenzyme A carboxylase (ACC) and AMPK at the α-T172 site, making it a valuable tool for research in type 2 diabetes.