mTOR Inhibitor

Everolimus-d₄ is the deuterium labeled Everolimus. Everolimus (RAD001) is a Rapamycin derivative and a potent, selective and orally active mTOR1 inhibitor. Everolimus binds to FKBP-12 to generate an immunosuppressive complex. Everolimus inhibits tumor cells proliferation and induces cell apoptosis and autophagy. Everolimus has potent immunosuppressive and anticancer activities.

Gedatolisib (Standard) is the analytical standard of Gedatolisib. This product is intended for research and analytical applications. Gedatolisib (PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ, and mTOR with IC50s of 0.4 nM, 5.4 nM and 1.6 nM, respectively. Gedatolisib is equally effective in both complexes of mTOR, mTORC1 and mTORC2.

Methyl Eugenol (Standard) is the analytical standard of Methyl Eugenol. This product is intended for research and analytical applications. 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.

HTH-01-091 is a potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor, with an IC₅₀ of 10.5 nM. HTH-01-091 also inhibits PIM1/2/3, RIPK2, DYRK3, smMLCK and CLK2. HTH-01-091 can be uesd for breast cancer research.

Kuwanon H is a selective non-peptide bombesin receptor antagonist and platelet activation inhibitor. Kuwanon H also acts as a specific antagonist of GRP-preferring receptors, with a K_i value of 290 nM for mouse GRP-R and 6500 nM for rat NMB-R. Kuwanon H inhibits the phosphorylation of AKT, mTOR, ERK, cPLA₂ and p38, and upregulates TRIB3. It induces endoplasmic reticulum stress, apoptosis and autophagosome formation. Kuwanon H blocks calcium mobilization, mitogenic signaling, DNA synthesis, dense granule secretion, thromboxane A₂ generation and integrin αIIb/β₃ activity. It inhibits collagen-induced platelet aggregation and fibronectin adhesion, and delays clot retraction. Kuwanon H inhibits melanoma cell growth in vitro and in vivo, and enhances the sensitivity of melanoma cells to CDDP. It can be used in research related to melanoma, small cell lung cancer and thrombosis.

8-Aminoadenosine (8-NH2-Ado), a RNA-directed nucleoside analogue, reduces cellular ATP levels and inhibits mRNA synthesis. 8-Aminoadenosine blocks Akt/mTOR signaling and induces autophagy and apoptosis in a p53-independent manner. 8-Aminoadenosine has antitumor activity.

AGPAT4-IN-1 (Compound CL26) is a covalent AGPAT4 inhibitor with an IC₅₀ of 795 nM. AGPAT4-IN-1 covalently binds to AGPAT4 at Cys²²⁸ and significantly inhibits acyltransferase activity, LPA-to-PA conversion and downstream mTOR/S6K pathways. AGPAT4-IN-1 sensitizes hepatocellular carcinoma (HCC) tumors to Sorafenib (HY-10201) and significantly induces apoptosis with a synergistic response. AGPAT4-IN-1 has antitumor activity and reduces tumorigenicity and stemness in HCC xenograft mouse models.

Succinylsulfathiazole (Succinylsulphathiazole) is a long-acting sulfonamide antibiotic with localized gut-specific antibacterial activity and is orally active. Succinylsulfathiazole inhibits bacterial folate synthesis, reduces coliform counts, suppresses intestinal bacterial growth and vitamin biosynthesis, and depletes gut folate-producing bacteria. Succinylsulfathiazole modulates hepatic mTOR signaling, diminishes cecal fermentation, decreases hepatic folate levels and total folate excretion, elevates nitrogen excretion and reduces the fermentability of certain dietary fibers. Succinylsulfathiazole induces folate deficiency and triggers biotin- and folate-related nutritional deficiency symptoms in rats and C57BL/6 mice.

WRX606 is an orally active nonrapalog inhibitor for mTOR complex 1 (mTORC1M). WRX606 inhibits the phosphorylation of mTORC1 substrate S6 kinase 1 (S6K1) (IC₅₀ = 10 nM) and eukaryotic translation initiation factor 4E binding protein (p-4E-BP1) (IC₅₀ = 0.27 μM) in MCF-7 cells. WRX606 suppresses tumor growth in mice without promotion of metastasis. WRX606 can be studied in research as an antitumor agent.

(32-Carbonyl)-RMC-5552 is a potent mTOR inhibitor. (32-Carbonyl)-RMC-5552 inhibits mTORC1 and mTORC2 substrate (p-P70S6K-(T389), p-4E-BP1-(T37/36), AND p-AKT1/2/3-(S473)) phosphorylation with pIC₅₀s of > 9, >9 and between 8 and 9, respectively (patent WO2019212990A1, example 2).

Rapamycin (Sirolimus) GMP Like is Rapamycin (HY-10219) produced by using GMP like guidelines. GMP Like small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. 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.

SKLB-D18 is an orally active ERK1/2/ERK5 inhibitor, with an IC₅₀ of 38.69 nM and a K_d of 126.9 nM against human ERK1, an IC₅₀ of 40.12 nM and a K_d of 209.8 nM against ERK2, and an IC₅₀ of 59.72 nM and a K_d of 468.2 nM against ERK5. SKLB-D18 inhibits cancer cell proliferation, induces G0/G1 cell cycle arrest and apoptosis. SKLB-D18 reduces the levels of p-ERK5, p-RSKp90, p-c-Myc and c-Myc, and upregulates the level of p-ERK1/2, thereby inhibiting the ERK1/2/5 pathway in cells. SKLB-D18 increases LC3B-II accumulation, and decreases the levels of p62, p-mTOR and p-p70S6K. SKLB-D18 elevates the levels of ROS, lipid peroxidation and free ferrous ions, reduces the levels of NCOA4 and GPX4, and induces ferritin autophagy-dependent ferroptosis in cancer cells. SKLB-D18 exhibits antitumor activity in a triple-negative breast cancer xenograft mouse model. SKLB-D18 can be used in research related to triple-negative breast cancer.

FT-1518 is a new generation selective, potent and oral bioavailable mTORC1 and mTORC2 inhibitor, and exhibits antitumor activity.

Itacnosertib hydrochloride (TP-0184 hydrochloride) is the inhibitor for FLT3, ACVR1 (ALK2, IC₅₀=8 nM) and JAK2 (IC₅₀=8540 nM). Itacnosertib hydrochloride exhibits anti-leukemic activity.

DEPTOR-IN-1 is a novel putative DEPTOR inhibitor with a K_d value of 9.3 μM.

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

SIRT6-IN-3 (compound 8a) is a selective inhibitor of SIRT6 (IC₅₀=7.49 μM). SIRT6-IN-3 inhibits pancreatic ductal adenocarcinoma (PDAC) cells proliferation and induces apoptosis. SIRT6-IN-3 increases the sensitivity of cancer cells to gemcitabine (HY-17026) via blocking the DNA damage repair pathway. SIRT6-IN-3 is used in pancreatic cancer research.

Veratramine (NSC17821; NSC23880) (Standard) is the analytical standard of Veratramine (HY-N0837). This product is intended for research and analytical applications. Veratramine (NSC17821; NSC23880) is an orally active inhibitor of the PI3K/Akt/mTOR signaling pathway and a SIGMAR1 modulator. Veratramine induces autophagic apoptosis of tumor cells, arrests the cell cycle at the G0/G1 phase, and inhibits epithelial-mesenchymal transition (EMT)-related proteins to reduce tumor migration. Veratramine reduces spinal cord and sciatic nerve pathological damage in a neuropathy model by inhibiting SIGMAR1 binding to NMDAR and phosphorylation of NMDAR Ser896. Veratramine has anti-tumor proliferation, apoptosis induction, anti-inflammatory and neuroprotective activities, and can be used in the study of cancers such as liver cancer and osteosarcoma, as well as diabetic peripheral neuropathy.

ASCT2-IN-2 (compound 25e) is an ASCT2 inhibitor with IC₅₀ of 5.14 μM. ASCT2-IN-2 regulates amino acid metabolism as well as mTOR signaling and thereby induces cell apoptosis. ASCT2-IN-2 inhibits tumor growth.

Rhodiolin, a flavonoid, is an orally active glucose 6-phosphate isomerase (GPI) inhibitor. Rhodiolin inhibits papillary thyroid cancer (PTC) by targeting glycolysis enzyme glucose 6-phosphate isomerase GPI and suppressing PI3K/AKT/mTOR phosphorylation and induce apoptosis. Rhodiolin as a NS2B-NS3 protease inhibitor can disrupt dengue viral replication. Rhodiolin is also a potential candidate for developing anticancer strategies inhibiting CK1ε kinase. Rhodiolin can be used for the study of anti-tumor and anti-viral .