XL388

SKU: orb1223368

Description

XL388 is a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR). XL388 inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. XL388 displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of XL388 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.

Images & Validation

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Key Properties

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CAS Number	1251156-08-7
MW	455.5
Purity	>98% (HPLC)
Formula	C₂₃H₂₂FN₃O₄S
SMILES	Cc1c(ccc(c1F)S(=O)(=O)C)C(=O)N1CCOc2c(C1)cc(cc2)c1cnc(cc1)N
Target	Glucokinase
Solubility	DMSO : 50 mg/mL. 109.77 mM;

Bioactivity

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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)).

In Vitro

XL388 (Compound 28) also inhibits DNA-PK with an IC50 of 8.831 μM. XL388 inhibits cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. XL388 acts in an ATP-competitive manner, with a linear increase in IC50 values with increasing ATP concentration. XL388 shows a dose-dependent effect in promoting MG-63 cell apoptosis. XL388 (100 nM) induces apoptosis in other two OS cell lines (U2OS and SaOs-2), but not in non-cancerous MC3T3-E1 cells. XL388 potently inhibits activation of both mTORC1 and mTORC2 in MG-63 cells. The effect of XL388 on mTORC1/2 activation is again dose-dependent. Further, mTORC1/2 activation is almost blocked in XL388 (100 nM)-treated U2OS cells, SaOs-2 cells and primary human OS cells.

Storage & Handling

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Storage	Storage temperature: -20°C. Stability: ≥ 2 years
Expiration Date	12 months from date of receipt.
Disclaimer	For research use only

Alternative Names

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XL388 | XL-388 | XL 388

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Gene Symbol

Glucokinase

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XL388 (orb1223368)

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Purity:	99.39%
CAS Number:	1251156-08-7
MW:	455.5
Formula:	C₂₃H₂₂FN₃O₄S

CAS Number:	2250061-94-8
MW:	484.54
Formula:	C₂₄H₂₅FN₄O₄S

XL388

Description

Images & Validation

Key Properties

Bioactivity

Storage & Handling

Alternative Names

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XL388 (orb1223368)

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