WAY-600 is a selective single digit nanomolar ATP-competitive mTOR inhibitor with an IC50 of about 9 nM. It has significant selectivity for these enzymes over phosphatidylinositol 3-kinase (PI3K) isofoms (>100-fold). With the 11% suppression by rapamycin, WAY-600 treated HEK293 cells indicated a 50% inhibition of polysomes. And WAY-600 blocked mTORC2-dependent phosphorylation of AKT in vitro and in vivo acutely. Without significant inhibition of P-AKT(T308), WAY-600 inhibited the mTORC1 substrate P-S6K(T389) and mTORC2 substrate P-AKT(S473) at submicromolar concentrations in various cancer cells.
Cell Experiment | |
---|---|
Cell lines | MDA361 and U87MG cells |
Preparation method | Cell lines of Rat1, HEK293, MDA-MB-361, MDA-MB-468, MDA-MB-231, LNCap, DU145, U87MG, A498, HCT116, and HT29 were obtained from the American Type Culture Collection. PC3MM2 was obtained from Dr. Carolyn Discafani (Wyeth Discovery Oncology). All cells were cultured using standard cell culture methods. For tumor cell growth assays, cells were plated in 96-well culture plates at 1000 to 3000 cells per well for 24 h, treated with DMSO or various doses of mTOR inhibitors. Viable cell densities were determined three days later by MTS assay employing an assay kit (CellTiter 96® AQueous, Cat # G5421, Promega) following the kit assay protocol. The effect of each treatment was calculated as percent of control growth relative to the DMSO-treated cells grown in the same culture plate. Inhibitor dose response curves were plotted for determination of IC50 values. |
Concentrations | 0.01~100 μM |
Incubation time | 3 days |
Animal Experiment | |
---|---|
Animal models | PC3MM2 tumors xenograft model in BALB/c nu/nu female mice |
Formulation | 5% ethanol, 5% polysorbate 80, 5% polyethylene glycol-400 |
Dosages | 50mg/kg on days 0 to 4 once daily or twice daily |
Administration | i.p. |
Molecular Weight | 494.59 |
Formula | C28H30N8O |
CAS Number | 1062159-35-6 |
Solubility (25°C) | DMSO ≥ 21 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Related mTOR Products |
---|
Zederone
Zederone, a germacrane-type sesquiterpene, has potently cytotoxic against human white blood cancer cells and human prostate cancer cells. Zederone significantly inhibits the proliferation and downregulates the protein expressions of mTOR, and phosphorylated p70 S6 kinase (p-p70s6K) in SKOV3 cells. |
MHY-1685
MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, provides opportunities to improve hCSC-based myocardial regeneration. |
RMC-6272
RMC-6272 (RM-006) is a bi-steric mTORC1-selective inhibitor. RMC-6272 exhibits potent and selective (> 10-fold) inhibition of mTORC1 over mTORC2. RMC-6272 shows improved inhibition of mTORC1 in comparison to Rapamycin, and induces more cell death in TSC2 null tumors. |
eCF309
eCF309 is a potent and highly selective mTOR inhibitor with remarkably low off-target activities (IC50 = 10-15 nM, both in vitro and in cells). |
PQR626
PQR626, a rapamycin derivative, is a potent, selective, orally active, and brain-penetrant mTOR inhibitor, with an IC50 and Ki of 5 nM and 3.6 nM, respectively. PQR626 can be can be used for the research of neurological disorders. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.