PI3K/Akt/mTOR

GSK-3β/G9a-IN-1 is a selective inhibitor of GSK-3β and G9a, acting through competitive mechanisms with IC50 values of 0.8 μM and 1.1 μM, respectively. This compound is effective in lowering tau phosphorylation and reducing Aβ aggregation, making it relevant for Alzheimer's disease research. Additionally, GSK-3β/G9a-IN-1 influences chromatin dynamics by inhibiting H3K9me2 and modulating members of the SAGA complex. Its ability to improve memory and restore social behaviors highlights its potential as a therapeutic agent in neurodegenerative conditions.

Aschantin is a bisepoxylignan that acts as a potent mTOR kinase inhibitor. This compound demonstrates significant biological activities, including antiplasmodial effects, calcium channel antagonism, and the inhibition of platelet activating factor. Additionally, Aschantin serves as an inhibitor of Cytochrome P450 and UGT enzymes, making it a valuable tool for chemoprevention research and various biochemical studies.

Sulindac sulfone is an mTORC1 pathway inhibitor and an active metabolite of Sulindac. It has been shown to effectively inhibit the growth of colon cancer cells and induce cell cycle arrest, making it a valuable tool in cancer research. This compound is primarily utilized to study the role of mTORC1 in tumorigenesis and to explore potential therapeutic strategies against colorectal cancer.

KS-99 is an inhibitor that targets both tubulin polymerization and the Akt signaling pathway. This compound demonstrates significant biological activity by inhibiting cancer cell proliferation and inducing apoptosis in various cancer cell types. KS-99 is suitable for research applications involving colorectal cancer, breast cancer, lung epithelial cancer, and melanoma.

VVD-442 is a selective inhibitor of PI3Kα that covalently binds to cysteine 242 within the RAS-binding domain of the PI3K p110α subunit. This binding induces conformational changes that disrupt the interaction between PI3K p110α and RAS proteins, effectively blocking RAS-mediated activation of PI3K. VVD-442 is applicable in research focusing on RAS-mutant cancers and HER2-overexpressing tumors, providing valuable insights into therapeutic strategies targeting these pathways.

LAS195319 is a potent and orally active inhibitor of PI3Kδ, exhibiting an IC50 of 0.5 nM. This compound demonstrates high selectivity against a wide array of proteins, lipid kinases, and GPCRs. LAS195319 effectively inhibits the infiltration of neutrophils and eosinophils, making it a valuable tool for research into respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD).

SH-273 is a potent dual-function compound that acts as a selective inhibitor of PI3Kγ with an IC50 of 7 nM while also stimulating STING function with an EC50 of 100 nM. This unique profile makes SH-273 a valuable tool for investigating signaling pathways involved in pancreatic cancer. Researchers can utilize SH-273 to explore the therapeutic potential of targeting PI3Kγ and enhancing STING-mediated immune responses in cancer models.

COX-2/PI3K-IN-2 is a potent inhibitor targeting both COX-2 and PI3K pathways, exhibiting an IC50 value of 2.78 nM for PI3K and a Ki value of 3.02 nM for COX-2. This compound demonstrates significant anti-inflammatory and anti-cancer activities, making it valuable for research in oncology and inflammatory disease studies. Its dual-target mechanism provides insights into the therapeutic potential of modulating these critical pathways.

XL388 is a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR).

IPI-145, also known as INK-1197, is an orally bioavailable, highly selective and potent small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities.

Akt-I-1 is a specific inhibitor of Akt1 (IC(50) 4.6 μM) and does not inhibit AKT2, or AKT3

AT13148 is a novel oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity, which shows a distinct mechanism of action from other AKT inhibitors.

VS-5584 is a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer.

MELK-IN-1 is a potent inhibitor of maternal embryonic leucine zipper kinase (MELK) with an IC50 and a Ki of 3 nM and 0.39 nM, respectively.

BIX 02565 is a novel inhibitor of ribosomal S6 kinase 2 with IC50 value of 1 nM.

SF1126 is a water soluble, small-molecule prodrug containing the pan-PI3K/mTOR inhibitor LY294002/SF1101 conjugated to the RGD-containing tetra-peptide SF1174 with potential antineoplastic and antiangiogenic activities.

TIC10 inactivates Akt and ERK to induce TRAIL through Foxo3a, possesses superior drug properties: delivery across the blood-brain barrier, superior stability and improved pharmacokinetics.

GSK 2334470 is a potent 3-phosphoinositide-dependent protein kinase (PDK1) inhibitor (IC50 ~ 10 nM).

GDC-0032 is a potent, next-generation PI3 inhibitor targeting PI3 alpha.

KP372-1 is a synthetic small molecule AKT inhibitor.

BX-517 is a potent and selective inhibitor of PDK1 that binds to the ATP binding pocket of the protein (IC50 = 6 nM).

PF-4989216 is a potent and selective PI3K inhibitor with IC50 of 2 nM, 142 nM, 65 nM, 1 nM, and 110 nM for p110α, p110β, p110γ, p110δ, and VPS34, respectively.

PF-04979064 is a highly potent and orally bioavailable PI3K/mTOR dual inhibitor.

GS-9901 is a highly selective and orally active PI3Kδ inhibitor, with an IC50 of 1 nM. Has potential to treat rheumatoid arthritis.

Afuresertib, also known as GSK2110183, is an orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. It binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.

mTOR inhibitor-2 is a highlt potent, selective and oral mTOR inhibitor with an IC50 of 7 nM. mTOR inhibitor-2 inhibits cellular phosphorylation of mTORC1 (pS6 and p4E-BP1) and mTORC2 (pAKT (S473)) substrates.

AZD2858 is a selective GSK-3 inhibitor with an IC50 of 68 nM, activating Wnt signaling, increases bone mass in rats.

CC-223 is a potent mTOR kinase inhibitor (IC50=16 nM), with >150-fold sensitivity over the related lipid kinase PI3K-alpha (IC50=4uM).

CGK733 is a selective inhibitor of ATR and ATM kinases. Induces cell death in prematurely senescent breast cancer cells.

AZ20 is a potent and selective inhibitor of ATR with an IC50 value of 5 nM.

Triciribine, also known as API-2, suppresses the phosphorylation level and kinase activity of Akt.

KU0060648 is a potent and selective inhibitor of DNA-dependent protein kinase (DNA-PK), (IC50 = 8.6 nM); with 20-1000 fold selectivity for DNA-PK over other PIKKs and a panel of 60 kinases. KU-0060648 enhances HDR efficiency and attenuates NHEJ frequency.

Borussertib is a covalent-allosteric and first-in-class inhibitor of protein kinase Akt, with an IC50 of 0.8 nM and a Ki of 2.2 nM for Aktwt.

BX-912 is an inhibitor of 3-Phosphoinositide-dependent Kinase-1 (PDK1).

NVP-BGT226, novel phosphoinositide 3-kinase/mTOR dual inhibitor, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo.

CH5132799 is a novel class I PI3K inhibitor, which exhibited a strong inhibitory activity especially against PI3Kα (IC(50)=0.014 μM).

WYE-687 is a novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin(mTOR).

WAY-600 is a single digit nanomolar inhibitor of the mTOR kinases, with significant selectivity for these enzymes over phosphatidylinositol 3-kinase (PI3K) isofoms (>100-fold).

CAY10505 is a potent inhibitor of PI3K, selectively inhibiting the γ isoform (IC50 = 30 nM) better than the α, β, and δ isoforms (IC50 = 0.94, 20, and 20 μM, respectively).

AS-604850 inhibited MCP-1-mediated monocyte chemotaxis with an IC50 value of 21 µM and reduced RANTES-induced peritoneal neutrophil recruitment in a murine model of leukocyte chemotaxis with an ED50 value of 42.4 mg/kg.

D-106669 is a highly potent and selective PI3K inhibitor, (PI3Kα IC50 <10 nM, >3 log selectivity against tyrosine or serine/threonine kinases, except ERK1 and 2).

The S-enantiomer of A66 is a potent inhibitor of the p110alpha isoform of PI 3-kinase (PIK3CA).

PP121 is a dual inhibitor of receptor tyrosine kinases (RTKs) (IC50 < 0.02 μM for Abl, Src, VEGFR-2 and PDGFR) and PI 3-K family kinases (IC50 < 0.06 μM for p110α, DNA-PK and mTOR).

TWS119 is a 4,6 disubstituted pyrrolopyrimidine that potently inhibits GSK3β with an IC50 value of 30 nM.1 At 400 nM.

GDC-0068 is a selective, ATP-competitive, pan-Akt inhibitor that targets Akt1, 2, and 3 with IC50 values of 5, 18, and 8 nM, respectively in cell-free assays

PX-866 is a small-molecule wortmannin analogue inhibitor of the alpha, gamma, and delta isoforms of phosphoinositide 3-kinase (PI3K) with potential antineoplastic activity.

Cenisertib (AS-703569) is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5 and FLT3.

AKT Kinase Inhibitor is an Akt kinase inhibitor with anti-tumor activity.

A-443654, a specific Akt inhibitor with Ki value of 160 pM, interferes with mitotic progression and bipolar spindle formation.

Dactolisib Tosylate (BEZ235 Tosylate) is a dual PI3K and mTOR kinase inhibitor with IC50 values of 4, 75, 7, 5 nM for PI3Kα, β, γ, δ, respectively. Dactolisib Tosylate (BEZ235 Tosylate) inhibits mTORC1 and mTORC2.