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XL388

Catalog No.S7035

For research use only.

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.

CAS No. 1251156-08-7

Selleck's XL388 has been cited by 1 Publication

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mTOR Signaling Pathway Map

Biological Activity

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.

Targets

mTORC1 ^[1]	mTOR ^[2]	mTORC2 ^[1]
8 nM	9.9 nM	166 nM

In vitro

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. ^[1]

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. ^[1] 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.^[2]

Protocol (from reference)

Animal Research:^[2]	Animal Models: MCF-7 xenograft tumors Dosages: 50, 100 mg/kg once daily Administration: Orally

References	[1] Nicole Miller, et al. Mol Cancer Ther, 2009, 8(12 Suppl):B146. [2] Takeuchi CS, et al. J Med Chem, 2013, 56(6), 2218-2234.

References

Solubility (25°C)

In vitro


In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing. Click to purchase: PEG400 Tween 80	30 mg/mL

Chemical Information

Molecular Weight	455.5
Formula	C₂₃H₂₂FN₃O₄S
CAS No.	1251156-08-7
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC1=C(C=CC(=C1F)S(=O)(=O)C)C(=O)N2CCOC3=C(C2)C=C(C=C3)C4=CN=C(C=C4)N

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