| Identification | Back Directory | [Name]
XL-388 | [CAS]
1251156-08-7 | [Synonyms]
XL388
XL-388
XL 388
CS-772
XL388, >=98%
XL-388;XL 388
XL-388 USP/EP/BP
Carbamazepine 298-46-4 three units, HPLC Purity : XL388
(7-(6-Aminopyridin-3-yl)-2,3-dihydrobenzo[f][1,4]oxazepin-4(5H)-yl)(3-fluoro-2-methyl-4-(methy
[7-(6-Amino-3-pyridinyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl][3-fluoro-2-methyl-4-(methylsulfonyl)phenyl]-methanone
Methanone, [7-(6-amino-3-pyridinyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl][3-fluoro-2-methyl-4-(methylsulfonyl)phenyl]-
[7-(6-Amino-3-pyridinyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl][3-fluoro-2-methyl-4-(methylsulfonyl)phenyl]-methanone XL388 | [Molecular Formula]
C23H22FN3O4S | [MDL Number]
MFCD24386875 | [MOL File]
1251156-08-7.mol | [Molecular Weight]
455.5 |
| Chemical Properties | Back Directory | [Melting point ]
>188oC (dec.) | [Boiling point ]
738.6±60.0 °C(Predicted) | [density ]
1.354±0.06 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
6.22±0.13(Predicted) | [color ]
Off-White to Pale Yellow | [Stability:]
Hygroscopic |
| Hazard Information | Back Directory | [Uses]
XL388 is a highly potent, orally bioavailable, selective, ATP-competitive mammalian target of rapamycin (mTOR) inhibitor. XL388 has shown significant and dose-dependent antitumor activity in athymic nude mice implanted with human tumor xenografts. | [Biological Activity]
XL388 is a potentselectiveorally bioavailable ATP-competitive inhibitor of mammalian target of rapamycin (mTOR) with an IC50 of 9.9 nM for mTOR8 nM for mTORC1166 nM for mTORC2and 1000-fold selectivity for mTOR over the closely related PI3K kinases and a panel of 141 protein kinases tested. XL388 blocked mTORC1 phosphorylation of p70S6K (T389) with an IC50 value of 94 nM and blocked mTORC2 phosphorylationof AKT (S473) with an IC50 value of 350 nM. XL388 showed complete tumor growth inhibition in mice bearing MCF-7 xenograft tumors. | [in vivo]
To assess the pharmacodynamic effects of XL388 (Compound 28) on the mTOR pathway signaling, athymic nude mice bearing PC-3 prostate tumors are dosed orally at 100 mg/kg of XL388. Rapamycin is also administered intraperitoneally at 5 mg/kg as a reference. Plasma and tumor samples are collected at 1, 4, 8, 16, 24, and 32 h for XL388 and at 4 h for Rapamycin after dosing and homogenized with buffer. Tumor lysates from each animal (n=5) are then pooled for each group and analyzed by immunoblot for levels of phosphorylated p70S6K, S6, 4E-BP1, and AKT. XL388 has moderate terminal elimination half-life (t1/2=1.35 h, 0.45 h, 6.11 h and 0.86 h for mouse (10 mg/kg, iv), rat (3 mg/kg, iv), dog (3 mg/kg, iv), monkey (3 mg/kg, iv))[1]. | [IC 50]
mTOR: 9.9 nM (IC50); mTORC1; mTORC2; DNA-PK: 8.831 μM (IC50) | [storage]
Store at -20°C |
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