WYE-354 is a potent and ATP competitive inhibitor of mTOR (IC50 = 5 nM), with significant selectivity over PI3K isofoms (>100-fold). WYE-354 is equally potent against mTORC1 and mTORC2 activities in HEK293 immune complex kinase assays using S6K and Akt as the respective substrate (IC50 <200 nM) and effectively blocks cellular phosphorylation of S6K on T389 and Akt on S473 both in cultures and in a murine xenograft model, resulting in a significant suppression of PC3MM2-derived tumor growth (by 86% on day 7; 50 mg/kg, i.p twice per day) in vivo.
 |
Source | Oncotarget (2015). Figure 1. WYE-354 |
| Method | MTS assay | |
| Cell Lines | Western blot analysis | |
| Concentrations | 1 μM | |
| Incubation Time | 24, 48, and 72 h | |
| Results | WYE-354 significantly reduced cell viability starting at a 1 μM concentration after a 24 hours exposure, in both studied cell lines |
| Cell Experiment | |
|---|---|
| Cell lines | Cell lines of Rat1, HEK293, MDA-MB-361, MDA-MB-468, MDA-MB-231, LNCap, DU145, U87MG, A498, HCT116, and HT29 |
| Preparation method | Tumor cell growth assays. |
| Concentrations | 0~100 μ M |
| Incubation time | 3 days |
| Animal Experiment | |
|---|---|
| Animal models | PC3MM2 tumors xenograft in BALB/c nu/nu female mice |
| Formulation | formulated in 5% ethanol, 5% polysorbate 80, 5% polyethylene glycol-400 |
| Dosages | a single i.p. injection with 50 mg/kg |
| Administration | i.p. |
| Molecular Weight | 495.5 |
| Formula | C24H29N7O5 |
| CAS Number | 1062169-56-5 |
| Solubility (25°C) | DMSO 90 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.
