mTOR Inhibitor

PI3K/mTOR Inhibitor-4 is an orally active pan-class I PI3K/mTOR inhibitor. PI3K/mTOR Inhibitor-4 has enzymatic inhibition activity for PI3Kα, PI3Kγ, PI3Kδ and mTOR with IC₅₀ values of 0.63 nM, 22 nM, 9.2 nM and 13.85 nM, respectively. PI3K/mTOR Inhibitor-4 can be used for the research of cancer.

WYE-23 is a mTOR inhibitor, and IC₅₀ is 0.45 nM. It is selective to PI3Kα and IC₅₀ is 661 nM. WYE-23 has antitumor activity.

ASCT2-IN-1 (compound 20k) is an ASCT2 inhibitor with IC₅₀ values of 5.6 μM and 3.5 μM in cells A549 and HEK293, respectively. ASCT2-IN-1 induces cell apoptosis. ASCT2-IN-1 inhibits tumor growth.

HBS-101 is a selectively, orally active, brain-penetrant, Midkine (MDK) inhibitor (K_D = 38.4 nM). HBS-101 significantly reduces cell viability, clonogenic survival, and invasiveness and increases apoptosis. HBS-101 involves suppression of the Akt/mTOR, STAT3, and NF-κB pathways. HBS-101 can be used for the study of Triple-negative breast cancer (TNBC).

6'''-Feruloylspinosin is an orally active RORα activator that crosses the blood-brain barrier, with a K_d of 0.308 μM, and is found in natural sources. 6'''-Feruloylspinosin modulates AMPK and mTOR phosphorylation. 6'''-Feruloylspinosin promotes autophagy through the AMPK/mTOR signaling pathway, inhibits GSK3β phosphorylation at Tyr216, and activates the PGC-1α/Nrf2/HO-1 pathway. 6'''-Feruloylspinosin regulates neurotransmitter levels, enhances mRNA expression of GABA_A α1, α5, and GABA_B R1 receptor subunits, increases brain 5-HT and GABA, restores melatonin levels, and ameliorates anxiety-like behaviors. 6'''-Feruloylspinosin regulates oxidative stress homeostasis, inhibits mitochondrial dysfunction, decreases MDA while increasing GSH. 6'''-Feruloylspinosin can be used for research on Alzheimer's disease, acute myocardial infarction, heart failure with insomnia, and insomnia.

Meranzin hydrate is an orally active antidepressant and GHSR modulator. Meranzin hydrate significantly upregulates the expression levels of brain-derived neurotrophic factor and p-mTOR in the hippocampus via the ghrelin-growth hormone secretagogue receptor pathway. Meranzin hydrate regulates blood oxygen level-dependent signals in the hippocampus-thalamus-basal ganglia circuit, attenuates reward system activation, and promotes the normalization of related hormone levels. Meranzin hydrate effectively ameliorates depression-like behaviors and gastrointestinal hypomotility, and can be used in research related to depression and major depressive disorder.

Diphenyl disulfide (Phenyl disulfide) is an organic disulfide compound. Diphenyl disulfide inhibits the PI3K/AKT/mTOR pathway, and induces ferroptosis (ferroptosis), apoptosis (apoptosis) and autophagy (autophagy) in cancer cells. Diphenyl disulfide downregulates GPX4 expression, inhibits NRF2 phosphorylation, induces lipid peroxidation, promotes xCT ubiquitination, induces proteolytic cleavage of p21 Bax into p18 Bax, and suppresses cell proliferation and viability. Diphenyl disulfide can be used in research related to melanoma and breast cancer.

MT 63-78 is a specific and potent direct AMPK activator with an EC₅₀ of 25 μM. MT 63–78 also induces cell mitotic arrest and apoptosis. MT 63-78 blocks prostate cancer growth by inhibiting the lipogenesis and mTORC1 pathways. MT 63-78 has antitumor effects.

IBL-302 (AMU302) is an orally available dual-signaling inhibitor of PIM and PI3K/AKT/mTOR with activity against breast cancer and neuroblastoma. IBL-302 demonstrated in vivo efficacy in a nude mouse xenograft model, inhibiting trastuzumab (HY-P9907) resistance challenges. IBL-302 also enhances the effects of common cytotoxic chemotherapy drugs cisplatin (HY-17394), doxorubicin (HY-15142A), and etoposide (HY-13629).

6-Methoxydihydrosanguinarine is an alkaloid with activity across multiple cancer cell types. 6-Methoxydihydrosanguinarine activates IRE1/JNK signaling, blocks Akt/mTOR and PI3K/AKT/mTOR pathways, reduces expression of Cdc25C, CyclinB1, Cdc2, YAP/TAZ, Survivin, GPX4, and EGFR, upregulates IRE1 and DR5, and activates JNK and caspases. 6-Methoxydihydrosanguinarine induces apoptosis, G2/M phase arrest, DNA damage, ROS generation, lipid peroxidation, ferroptosis, autophagy, and suppresses cancer cell growth. 6-Methoxydihydrosanguinarine disruptes the biofilm formation of Candida albicans (C. albicans). 6-Methoxydihydrosanguinarine can be used for the research of non-small cell lung cancer, hepatocellular carcinoma, melanoma, colon carcinoma, ovarian cancer and breast cancer.

SU212 is a podophyllotoxin-derived ENO1 inhibitor and AMPK activator. SU212 can selectively induce oxidative phosphorylation, reduce glycolysis activity and glucose uptake in tumor cells, and directly bind to ENO1 without affecting these pathways in normal cells. SU212 induces apoptosis and promotes ENO1 degradation via proteasomal and autophagic pathways without inhibiting the catalytic activity. SU212 leads to mitotic arrest and apoptosis in TNBC (triple-negative breast cancer) cells by activating AMPK, demonstrating potent anti-tumor activity in vitro. SU212 inhibits tumor growth and metastasis in syngeneic, xenograft, and diabetic mouse models, exhibiting an excellent safety profile. SU212 can be used in research on t TNBC, diabetes, and fatty liver disease.

Rapamycin-d₃ (Sirolimus-d_{3; AY-22989-d3; NSC 226080-d3}) is the deuterated-labeled Rapamycin (HY-10219). Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC₅₀ of 0.1 nM in HEK293 cells. Rapamycin is a molecular glue that binds FKBP12 and mTOR proteins together, thereby inhibiting mTOR kinase activity. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator, an immunosuppressant.

PI3K/mTOR Inhibitor-11 is an orally active PI3K/mTOR inhibitor (IC₅₀: 3.5, 4.6, and 21.3 nM for PI3Kα, PI3Kδ, and mTOR). PI3K/mTOR Inhibitor-11 regulates the PI3K/AKT/mTOR signaling pathway by inhibiting the phosphorylation of AKT and S6 proteins. PI3K/mTOR Inhibitor-11 can be used in the research of cancers.

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

Pomiferin (NSC 5113) acts as an potential inhibitor of HDAC, with an IC₅₀ of 1.05 μM, and also potently inhibits mTOR (IC₅₀, 6.2 µM).

Kuwanon G is a flavonoid compound and an antagonist of the bombesin receptor. Kuwanon G has multiple activities such as bactericidal, anti-tumor, anti-inflammatory, antioxidant, anti-atherosclerotic, and neuroprotective effects. Kuwanon G exhibits strong antibacterial activity against oral pathogens, especially cariogenic bacteria and periodontal pathogens. Kuwanon G can induce apoptosis and inhibit proliferation, migration, and invasion of tumor cells. Kuwanon G can be used in the research of diseases such as gastric cancer and atherosclerosis.

Brassinin is an indole derivative found in cruciferous plants. Brassinin acts as an IDO inhibitor (K_i = 97.7 μM). Brassinin inhibits angiogenesis and induces apoptosis, autophagy, paraptosis, ROS production, and ER stress. Brassinin selectively stimulates lysosomal degradation of Tie2 and promotes lysosomal and proteasomal degradation of FGFR1 in endothelial cells, downregulating AKT and ERK phosphorylation. Brassinin inhibits endothelial cell proliferation, migration, tube formation, spheroid sprouting, and angiogenesis. Brassinin inhibits PI3K/Akt/mTOR/S6K1 signaling, upregulates p21 and p27, and induces G1 phase cell cycle arrest through RB hypophosphorylation. Brassinin inhibits tyrosinase catalytic activity, reduces tyrosinase mRNA, and inhibits MITF nuclear translocation. Brassinin is used for research on triple-negative breast cancer, chronic myeloid leukemia, colon cancer, glioma, atherosclerosis, and skin cancer.

KTC1101 is an orally active pan-PI3K inhibitor. KTC1101 can inhibit the PI3K signaling pathway, reduce downstream AKT and mTOR phosphorylation, and reduces the expression of Ki67. The anti-tumor effect of KTC1101 has a dual mechanism of action: directly inhibiting tumor cell growth and dynamically enhancing immune response.

MKC-1 (Ro-31-7453) is an orally active and potent cell cycle inhibitor with broad antitumor activity. MKC-1 inhibits the Akt/mTOR pathway. MKC-1 arrests cellular mitosis and induces cell apoptosis by binding to a number of different cellular proteins including tubulin and members of the importin β family.

Macranthoside B is an apoptosis inducer with in vitro and in vivo anticancer activity. Macranthoside B induces autophagy and ferroptosis in cancer cells. Macranthoside B induces intracellular ROS accumulation, activates AMPK, inhibits mTOR and P70S6 kinase phosphorylation, and modulates Bcl-2/Bax expression. Macranthoside B activates caspase-3, caspase-9, and the intrinsic caspase cascade, induces PARP cleavage/degradation, and inhibits NRF2 signaling. Macranthoside B disrupts iron homeostasis via NCOA4-dependent ferritinophagy, up-regulates Lip-ROS, reduces mitochondrial membrane potential, and activates the JNK pathway. Macranthoside B can be used for the research of ovarian cancer, hepatoma, gastric carcinoma, breast carcinoma, colon carcinoma, glioma, melanoma, adenocarcinoma of the esophagogastric junction, and cervical cancer.