mTOR Inhibitor

Rubrofusarin gentiobioside (Rrubrofusarin-6-β-gentiobioside) is an orally active weak inhibitor of PTP1B and MAO-A (IC₅₀ >100 μM), and its glycosylation modification results in lower biological activity than its aglycone Rubrofusarin (HY-130307). Rubrofusarin gentiobioside promotes AMPK phosphorylation in an LKB1-independent manner and inhibits the mTOR signaling pathway, thereby downregulating the expressions of PPARγ, C/EBPα, as well as FAS, LPL and aP2. Rubrofusarin gentiobioside inhibits lipid accumulation, reduces body weight and epididymal white adipose tissue volume, improves fatty liver, and shows no cytotoxicity to hepatocytes. Rubrofusarin gentiobioside is widely used in obesity-related studies.

Jervine (11-Ketocyclopamine) is an orally active steroidal alkaloid and Hedgehog signaling pathway inhibitor. Jervine can be isolated from Veratrum californicum. Jervine regulates Wnt, inhibits the AKT/mTOR signaling pathway, and activates the AMPK signaling pathway. Jervine induces DNA damage, Apoptosis, Autophagy, ROS production and Mitochondrial damage. Jervine exhibits anti-cancer and anti-inflammatory activities. Jervine reduces tumor growth rate and weight in xenograft models. Jervine can be used in studies related to triple-negative breast cancer, nasopharyngeal carcinoma and non-small cell lung cancer.

Schisantherin B (Gomisin-B) is a lignan compound and one of the active components of Schisandra chinensis. Schisantherin B activates the PI3K/AKT signaling pathway, restores the activity of GSK3β, and reduces the hyperphosphorylation of tau protein in hippocampal and cerebral cortical tissues. Schisantherin B upregulates the level of GLT-1, decreases the expression of pro-inflammatory cytokines TNF-α/IL-1β/IL-6, upregulates the expression of IL-10, and inhibits cell apoptosis. Schisantherin B is applicable to the research of spinal cord injury, Alzheimer's disease and depression.

GNE-493 is a potent, selective, and orally available dual pan-PI3-kinase/mTOR inhibitor with IC₅₀s of 3.4 nM, 12 nM, 16 nM, 16 nM and 32 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR.

PI3K/mTOR Inhibitor-2 is a potent dual pan-PI3K/mTOR inhibitor with IC₅₀s of 3.4/34/16/1 nM for PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ and 4.7 nM for mTOR. Antitumor activity.

Ifupinostat (BEBT-908) is a blood-brain barrier-permeable PI3K/HDAC inhibitor. Ifupinostat exerts anticancer activity against hematologic malignancies, lung cancer, colon cancer, brain cancer and other cancers. Ifupinostat inhibits the PI3K/AKT/mTOR signaling pathway, suppresses c-Myc expression and induces ferroptosis. Ifupinostat can be used in tumor research.

L-Glutamine-1-¹³C is the ¹³C-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.

PKI-179 is a potent and orally active dual PI3K/mTOR inhibitor, with IC₅₀s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC₅₀s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo.

Guaiazulene is a bicyclic sesquiterpene. Guaiazulene exhibits various biological activities such as anti-inflammatory, antioxidant, hepatoprotective, antibacterial, and anti-tumor properties. Guaiazulene is also commonly used as a colorant in cosmetics. Guaiazulene shows in vitro cytotoxicity to rat neuronal cells and N2a neuroblastoma cells at high concentrations.

Izorlisib (CH5132799) is an orally active, selective Class I PI3K inhibitor with an IC₅₀ value of 14 nM against PI3Kα. Izorlisib specifically inhibits Class I PI3K (particularly PI3Kα and its mutants) and blocks the PI3K/Akt/mTOR pathway; this leads to cell cycle arrest at the G1 phase and apoptosis without triggering feedback activation of Akt by competitively binding to the ATP-binding site of PI3K. Izorlisib can be used in research on cancers harboring PIK3CA mutations or PTEN loss (such as breast, ovarian, prostate, and endometrial cancers).

Curzerenone is an orally active sesquiterpene compound and Antibacterial agent. Curzerenone can be isolated from Curcuma zedoaria and Curcuma aeruginosa plants. Curzerenone increases ROS levels, activates Apoptotic signaling pathways, and attenuates the PI3K/AKT/mTOR signaling pathway. Curzerenone exhibits anticancer activity against liver cancer and cervical cancer. Curzerenone has antioxidant effects. Curzerenone shows weak antibacterial activity against Escherichia coli. Curzerenone can be used in research related to hepatocellular carcinoma, cervical cancer, and Escherichia coli infection.

Dammarenediol II is a ginsenoside precursor. Dammarenediol II reduces the activity of O-GlcNAc transferase (OGT) and downregulates the global O-GlcNAcylation level. Dammarenediol II inhibits the phosphorylation of Akt, mTOR and GSK3β. Dammarenediol II inhibits human carboxylesterase activity, VEGF-induced ROS production, stress fiber formation and vascular endothelial cadherin disruption. Dammarenediol II promotes cell apoptosis (apoptosis), increases the levels of cleaved PARP1 and p53, and inhibits retinal microvascular leakage. Dammarenediol II can be used in studies related to liver cancer and diabetic retinopathy.

WAY-600 is a potent, ATP-competitive, and selective mTOR inhibitor with an IC₅₀ of 9 nM for recombinant mTOR enzyme. WAY-600 blocks mTOR complex 1/2 (mTORC1/2) assemble and activation.

mTOR inhibitor-1 (Compound C-4) is an ATP-Competitive mTOR inhibitor which can suppress cells proliferation and inducing autophagy.

HDACs/mTOR Inhibitor 1 is a dual HDACs and mTOR inhibitor, with IC₅₀s of 0.19 nM, 1.8 nM, 1.2 nM for HDAC1, HDAC6, mTOR, respectively. HDACs/mTOR Inhibitor 1 stimulates cell cycle arrest in G0/G1 phase and induces tumor cell apoptosis with low toxicity in vivo. HDACs/mTOR Inhibitor 1 can be used in the research of hematologic malignancies.

WYE-354 is an ATP-competitive mTOR inhibitor with an IC₅₀ of 5 nM. WYE-354 also inhibits PI3Kα and PI3Kγ with IC₅₀s of 1.89 μM and 7.37 μM, respectively. WYE-354 inhibits both mTORC1 and mTORC2. WYE-354 induces autophagy activation in vitro.

Simufilam hydrochloride (PTI-125 hydrochloride) is an orally active FLNA modulator. Simufilam hydrochloride restores NMDAR signaling and Arc expression. Simufilam hydrochloride inhibits overactive mTOR signaling by restoring the normal conformation of FLNA, improves insulin sensitivity, reduces Aβ₄₂-induced neuroinflammation and tau protein hyperphosphorylation. Simufilam hydrochloride can be used for research of Alzheimer's disease.

HZX-02-059 is an allosteric inhibitor of PIKFYVE, and a methuosis inducer. HZX-02-059 disrupts the PIKfyve/TFEB axis, suppresses tubulin polymerization, reduces phosphorylated mTOR levels, downregulates p53, PI3K/AKT, c-Myc, and NF-κB pathways. HZX-02-059 induces G₂/M cell cycle arrest, apoptosis, and inhibits cancer cell proliferation. HZX-02-059 can be used for the research of lymphoma, double-hit lymphoma, and B-cell acute lymphoblastic leukemia.

Ajugol is an orally active iridoid glycoside found in the traditional Chinese medicine Leonurus japonicus. Ajugol is an autophagy activator. Ajugol activates TFEB-mediated autophagy and lysosomal biogenesis. Ajugol also has anti-inflammatory effects. Ajugol has great potential in the research of asthma, non-alcoholic fatty liver disease (NAFLD), and osteoarthritis.

Lasiokaurin is an anticancer agent. Lasiokaurin can be isolated from Rabdosia rubescens (Hemsl.) H. Hara. Lasiokaurin inhibits the function of the PDPK1-AKT axis, with a K_d value of 75.93 μM for PDPK1. Lasiokaurin inhibits mTOR, STAT3, MAPK and NF-κB. Lasiokaurin reduces the mRNA and protein expression levels of PLK1. Lasiokaurin decreases DNA synthesis levels, induces cell Apoptosis, and regulates Autophagy processes. Lasiokaurin inhibits tumor growth in xenograft models. Lasiokaurin can be used in research related to nasopharyngeal carcinoma, triple-negative breast cancer.