mTOR Inhibitor

Desmethyl-VS-5584 is a dimethyl analog of VS-5584 which is an potent and selective mTOR/PI3K dual inhibitor with pyrido [2,3-d] pyrimidine structure.

Topoisomerase I-IN-25 is a moderate inhibitor of Topoisomerase I-mediated DNA relaxation. Topoisomerase I-IN-25 inhibits the cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways. Topoisomerase I-IN-25 downregulates Bcl-2, upregulates Bax, and induces Apoptosis, G2/M phase arrest, mitochondrial dysfunction, and reactive oxygen species accumulation. Topoisomerase I-IN-25 exhibits anticancer activity against hepatocellular carcinoma. Topoisomerase I-IN-25 can be used for research on hepatocellular carcinoma.

HN2210 is an mTORC2 inhibitor..

LGB321 is an inhibitor of PIM2-dependent multiple myeloma cell lines, effectively inhibiting proliferation and key signaling pathways such as mTOR-C1 and phosphorylation of BAD.

M-1111 is a Rapa-Link inhibitor. M-1111 is covalently linked by Rapamycin (HY-10219) and an inhibitor of the active site mTOR. M-1111 has strong inhibitory activity on the mTORC1 signaling pathway (pS6 and p4E-BP1). M-1111 has nanomolar-level inhibitory activity against various cancer cells. M-1111 completely inhibits p4E-BP1 without inhibiting pAkt S473. M-1111 can be used for research on liver cancer, kidney cancer, and colorectal cancer.

PP162 is a selective DNA-dependent protein kinase (DNA-PK) inhibitor with an IC₅₀ of 53 nM. PP162 selectively inhibits DNA-PK by binding to a conserved hydrophobic pocket. PP162 exhibits weak inhibitory activity against various tyrosine kinases and PI3K family members. PP162 can be used for research on selective kinase targeting.

ICSN3250 hydrochloride is a halitulin analogue and a mTORC1 inhibitor. ICSN3250 hydrochloride directly binds to mTOR's FRB domain and displaces phosphatidic acid (PA), reversing mTORC1 activation. ICSN3250 hydrochloride shows high cytotoxicity in cancer cells (nanomolar concentration) through a caspase-independent cell death mechanism. ICSN3250 hydrochloride specifically inhibits the mTORC1 pathway, inducing autophagy and G0-G1 cell-cycle arrest in cancer cells. ICSN3250 hydrochloride can be used for the study of cancer .

Tirzepatide sodium (LY3298176 sodium) is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide sodium exerts anti-apoptotic and pro-differentiation effects via the pAkt/CREB/BDNF cascade and miRNA in neurons; in the heart, it promotes BCAA catabolism and inhibits the mTOR pathway by mediating the dephosphorylation of BCKDHA; meanwhile, it effectively reduces insulin and leptin levels and suppresses inflammatory responses at the systemic level. Tirzepatide sodium can be used for research on myocardial infarction, colon cancer, diabetes, diabetic cognitive impairment, neurodegeneration, diabetes-related neuropathy, and obesity.

PI3K/mTOR-IN-18 (Compound 12) is a highly selective dual PI3K/mTOR inhibitor. PI3K/mTOR-IN-18 shows antitumor effects via competitive binding to PI3Kα (K_i=0.130 nM) and mTOR (K_i=0.111 nM). PI3K/mTOR-IN-18 blocks the PI3K/AKT/mTOR pathway and inhibits tumor cell proliferation (IC₅₀=144 nM). PI3K/mTOR-IN-18 is promising for research of solid tumors (e.g., breast, NSCLC).

PI3K/mTOR Inhibitor-14 (compound Y-2) is a potent PI3K and mTOR dual inhibitor with IC₅₀s of 171.4 nM and 10.1 nM, respectively. PI3K/mTOR Inhibitor-14 has antitumor activities.

mTOR/HDAC6-IN-1 is a potent mTOR and HDAC6 dual inhibitor (IC₅₀s of 133.7 nM and 56 nM for mTOR and HDAC6, respectively). mTOR/HDAC6-IN-1 can induce significant autophagy, apoptosis and suppress migration. mTOR/HDAC6-IN-1 has potential to research Triple-negative breast cancer (TNBC).

Daporinad (FK866) hydrochloride is a non-competitive inhibitor of nicotinamide phosphoribosyltransferase (Nampt), with a K_i value of 0.3 nM. Daporinad hydrochloride depletes NAD+ and ATP levels, inhibits mTORC1 and MAPK/ERK pathways, and activates TFEB to induce autophagy. Daporinad hydrochloride causes the depletion of the endoplasmic reticulum Ca²⁺ pool, ultimately weakening the mitogen-induced Ca²⁺ signal and the activation and function of T cells. Daporinad hydrochloride induces cell cycle arrest and apoptosis, and inhibits cell proliferation. Daporinad hydrochloride can be used for the study of myeloma, liver cancer, and immunosuppression.

Phanginin H is an Autophagy inducer with an IC₅₀ of 18.13 μM in PANC-1 cells. Phanginin H induces Reactive Oxygen Species accumulation and mitochondrial depolarization, activates AMPK signaling, inhibits mTORC1/ULK signaling and promotes autophagic flux, and simultaneously induces G2/M phase cell cycle arrest, thereby inhibiting PANC-1 cell proliferation, spheroid formation, and migration. Phanginin H can be used in research related to pancreatic ductal adenocarcinoma.

ROR1-IN-3 (Compound 24d) is a potent and highly selective ROR1 kinase inhibitor (IC₅₀ = 17.6 nM). ROR1-IN-3 demonstrates robust antitumor activity and inhibitory effect against ROR1 both in vitro and in vivo. ROR1-IN-3 has robust antiproliferative efficacy in vitro and in vivo. ROR1-IN-3 induces apoptosis in cancer cell lines. ROR1-IN-3 inhibits ROR1 downstream AKT/mTOR and NF-κB signaling pathway. ROR1-IN-3 can be studied in antitumor research.

Bisdemethoxycurcumin is an orally effective curcuminoid. Bisdemethoxycurcumin downregulates pro-inflammatory cytokines in macrophages by inhibiting the phosphorylation of PI3K/Akt and p38 MAPK. Bisdemethoxycurcumin relieves autophagy inhibition and promotes lipophagy to clear vascular smooth muscle foam cells by inhibiting the PDK1/Akt/mTOR pathway. Bisdemethoxycurcumin activates the cAMP/Epac/AMPKα axis and the NRF2/HO-1 antioxidant axis, thereby indirectly inhibiting the phosphorylation of NF-κB p65 and pro-inflammatory outputs such as IL-1β/IL-6/TNF-α, so as to alleviate pulmonary oxidative stress, inflammatory infiltration and pulmonary edema. Bisdemethoxycurcumin blocks NLRP3-mediated pyroptosis and protects cartilage extracellular matrix degradation by activating NRF2/HO-1. Bisdemethoxycurcumin also exerts a synergistic effect with potassium iodide against Candida.

PI3K/mTOR Inhibitor-7 (Compound 19i) is a potent and dual inhibitor of PI3K/mTOR. PI3K/mTOR Inhibitor-7 shows 4.7-fold higher potency than the positive control gedatolisib (0.3 vs. 1.4 μM, IC₅₀ values). PI3K/mTOR Inhibitor-7 significantly suppresses the PI3K/Akt/mTOR signaling pathway at 10 μM. PI3K/mTOR Inhibitor-7 has the potential for the research of cancer diseases.

PI3K/Akt/mTOR-IN-7 is an AKT/mTOR and JAK2/STAT3 inhibitor. PI3K/Akt/mTOR-IN-7 restores p-Akt, p-mTOR, and p-STAT3 expression, reduces pro-apoptotic Caspase-3 mRNA expression. PI3K/Akt/mTOR-IN-7 reduces intracellular ROS accumulation and inhibits NO production. PI3K/Akt/mTOR-IN-7 can be used for research on stroke, Alzheimer's disease and Parkinson's disease.

CAII/VII-IN-1 is an orally active hCA II (K_I = 12.3 nM), and hCA VII (K_I = 22.6 nM) inhibitor, showing no significant activity against hCA I. CAII/VII-IN-1 shows excellent neuroprotective activity in vivo Pilocarpine (HY-B0726A)-induced seizure model. CAII/VII-IN-1 can upregulate KCC2 and inhibit mTOR, exerting neuroprotective effects. CAII/VII-IN-1 does not show any significant neurotoxic effects or alterations in liver and kidney function. CAII/VII-IN-1 can be used for the study of epilepsy.

PI3K/Akt/mTOR-IN-6 (Compound JW4) is an orally active PI3K/Akt/mTOR pathway inhibitor. PI3K/Akt/mTOR-IN-6 induces Apoptosis in cells via the mitochondrial pathway. PI3K/Akt/mTOR-IN-6 shows potent anti-NSCLC activity.

Topo I/II-IN-2 (Compound 3g) is an inhibitor of Topo I and Topo II. Topo I/II-IN-2 inhibits NCI-H446 cells and NCI-H1048 cells with IC₅₀s of 1.30 μM and 1.42 μM, respectively. Topo I/II-IN-2 induces mitochondrial Apoptosis, mitochondrial dysfunction and activity generation. Topo I/II-IN-2 inhibits the PI3K/Akt/mTOR pathway. Topo I/II-IN-2 prevents SCLC (small cell lung cancer) cell proliferation, invasion, and migration in vitro. .