Molecular Weight(MW): 455.5
XL388 is a highly potent, selective, ATP-competitive inhibitor of mTOR with IC50 of 9.9 nM, 1000-fold selectivity over the closely related PI3K kinases.
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|Description||XL388 is a highly potent, selective, ATP-competitive inhibitor of mTOR with IC50 of 9.9 nM, 1000-fold selectivity over the closely related PI3K kinases.|
In MCF-7 cells, XL388 blocks mTORC1 phosphorylation of p70S6K (T389)with an IC50 value of 94 nM and blocks mTORC2 phosphorylationof AKT (S473) with an IC50 value of 350 nM. In vitro, XL388 inhibits the viability of solid and hematopoietic tumor cell lines. The proliferation IC50 is 1.37 μM in MCF-7 cell line. XL388 also synergizes with chemotherapeutics in cell-based assays to block cell viability. 
|In vivo||When dosed orally once daily in mice, XL388 shows robust anti-tumor activity in multiple xenograft models including > 100% tumor growth inhibition in the MCF-7 xenograft model.  XL388 displays good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. The mean plasma protein binding of XL388 in human, monkey, dog, rat, and mouse plasma is evaluated at 5 μM and is determined to be 86%, 90%, 89%, 85%, and 84%, respectively. Oral administration of XL388 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity. Strong inhibition of both mTORC1 and mTORC2 is achieved 4−8 h following administration orally at 100 mg/kg. Modest inhibition (39−45%) of phosphorylation of the PI3K target AKT (T308) is also observed 4−8 h post dose.|
|In vitro||DMSO||23 mg/mL (50.49 mM)|
|In vivo||Add solvents individually and in order:
30% PEG400+0.5% Tween80+5% propylene glycol
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
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