mTOR Inhibitor

Fusaric acid is an orally active multi-pathway inhibitor with the activity of inducing oxidative stress and apoptosis. Fusaric acid can chelate divalent metal cations, damage mitochondrial membrane structure, and activate apoptosis-related proteases such as Caspase-3/7, -8, and -9. Fusaric acid also regulates Bax/Bcl-2 protein, inhibits fibrosis-related signaling pathways such as NF-κB, TGF-β₁/SMADs, and PI3K/AKT/mTOR, and reduces collagen deposition. Fusaric acid is also a dopamine β-hydroxylase inhibitor, which reduces endogenous levels of norepinephrine and epinephrine in the brain, heart, spleen, and adrenal glands. Fusaric acid can play a role in myocardial fibrosis and improve cardiac hypertrophy in heart disease, and can also be used in the study of esophageal cancer and liver cancer.

OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC₅₀ of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC₅₀s of 22 nM and 65 nM, respectively.

VS-5584 is a pan-PI3K/mTOR kinase inhibitor with IC₅₀s of 16 nM, 68 nM, 42 nM, 25 nM, and 37 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively. VS-5584 simultaneously blocks mTORC2 as well as mTORC1.

Doxepin Hydrochloride is an orally active, blood-brain barrier penetrant tricyclic antidepressant with multiple activities including hypnosis, sedation, analgesia and vasodilation. Doxepin Hydrochloride enhances the expression of PSD-95 and synapsin 1 via the PI3K/AKT/mTOR signaling pathway, and is metabolized to DesmethylDoxepin Hydrochloride in vivo. Doxepin Hydrochloride can be used in research related to various diseases such as depression, anxiety, obesity and atopic dermatitis.

Methyl Eugenol is a bait that has oral activity against oriental fruit fly (Hendel).Methyl Eugenol has anti-cancer and anti-inflammatory activities. Methyl Eugenol can induce Autophagy in cells. Methyl Eugenol can be used in the study of intestinal ischemia/reperfusion injury.

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.

Raddeanin A is an oleanane-type triterpenoid saponin with oral activity. Raddeanin A inhibits SRC, mTOR, JNK, VEGFR2, NLRP3 inflammasome, Wnt/β-catenin, Wee1, PI3K/AKT signaling pathway, MAPK/ERK signaling pathway, AR-FL, AR-Vs, and downregulates the expression of p-PI3K and p-AKT. Raddeanin A inhibits osteoclast formation, bone resorption, osteolysis, cancer cell invasion, migration, proliferation, angiogenesis and epithelial-mesenchymal transition, while induces apoptosis, cell cycle arrest, ROS production, immunogenic cell death and dendritic cell maturation. Raddeanin A improves blood-retinal barrier function, alleviates inflammation, regulates the tumor microenvironment, and enhances the activity of anti-PD-1 antibody. Raddeanin A is applicable to the research of breast cancer-associated osteolysis, human osteosarcoma, colorectal cancer, glioblastoma, Alzheimer's disease, cholangiocarcinoma, melanoma, non-small cell lung cancer, castration-resistant prostate cancer and multiple myeloma.

Onatasertib (CC-223) is a potent, selective, and orally bioavailable inhibitor of mTOR kinase, with an IC₅₀ value for mTOR kinase of 16 nM. Onatasertib inhibits both mTORC1 and mTORC2.

Monepantel (AAD1566, NUZ-001), an antiparasitic agent, is an orally active mTOR inhibitor. Monepantel triggers autophagy through the deactivation of mTOR/p70S6K signalling pathway. Monepantel is a positive allosteric modulator of a nematode-specific clade of nAChR subunits. Monepantel can be used for the study of amyotrophic lateral sclerosis (ALS) and ovarian cancer.

α-solanine, a bioactive component and one of the major steroidal glycoalkaloids in Solanum nigrum, has been observed to inhibit growth and induce apoptosis in cancer cells.

GSK1059615 is a dual inhibitor of PI3Kα/β/δ/γ (reversible) and mTOR with IC₅₀ of 0.4 nM/0.6 nM/2 nM/5 nM and 12 nM, respectively.

PF-04979064 is a potent and selective PI3K/mTOR dual kinase inhibitor with K_is of 0.13 nM and 1.42 nM for PI3Kα and mTOR, respectively.

ETP-46464 is an effective mTOR and ATR inhibitor with IC₅₀s of 0.6 and 14 nM, respectively.

Voxtalisib (XL765) is a potent PI3K inhibitor, which has a similar activity toward class I PI3K (IC₅₀s=39, 113, 9 and 43?nM for p110α, p110β, p110γ and p110δ, respectively), also inhibits DNA-PK (IC₅₀=150?nM) and mTOR (IC₅₀=157?nM). Voxtalisib (XL765) inhibits mTORC1 and mTORC2 with IC₅₀s of 160 and 910 nM, respectively.

WYE-132 (WYE-125132) is a highly potent, ATP-competitive, and specific mTOR kinase inhibitor (IC₅₀: 0.19±0.07 nM; >5,000-fold selective versus PI3Ks). WYE-132 (WYE-125132) inhibits mTORC1 and mTORC2.

GNE-317 is a PI3K/mTOR inhibitor, is able to cross the blood-brain barrier (BBB).

PP121 is a multi-targeted kinase inhibitor with IC₅₀s of 10, 60, 12, 14, 2 nM for mTOR, DNK-PK, VEGFR2, Src, PDGFR, respectively.

L-Glutamine-¹³C₅,¹⁵N₂ is the ¹³C- and ¹⁵N-labeled L-Glutamine (HY-N0390). L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na⁺-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.

Lomitapide (AEGR-733; BMS-201038) mesylate is an orally active microsomal triglyceride transfer protein (MTP) inhibitor and a selective mTORC1 inhibitor with lipid-lowering activity and BBB permeability. Lomitapide mesylate significantly reduces plasma LDL levels by blocking the assembly and secretion of very-low-density lipoprotein (VLDL). Lomitapide mesylate inhibits mTORC1 in an ATP-dependent manner, thereby inducing AMPK-independent autophagic cell death and suppressing cancer cell growth and apoptosis. Lomitapide mesylate also enhances tumor infiltration of CD8⁺ T cells. In addition, Lomitapide mesylate inhibits HDAC, improves endothelial function, effectively alleviates vascular inflammation and oxidative stress, and exerts neuroprotective effects in a cerebral ischemia/reperfusion injury model. Lomitapide mesylate can be used in research on related diseases such as colorectal cancer, breast cancer, melanoma, ischemic stroke, and familial hypercholesterolemia.

Coenzyme Q0 (CoQ0) is a potent, oral active ubiquinone compound can be derived from Antrodia cinnamomea. Coenzyme Q0 induces apoptosis and autophagy, suppresses of HER-2/AKT/mTOR signaling to potentiate the apoptosis and autophagy mechanisms. Coenzyme Q0 regulates NFκB/AP-1 activation and enhances Nrf2 stabilization in attenuation of inflammation and redox imbalance. Coenzyme Q0 has anti-angiogenic activity through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling.