[CAS NO. 406228-55-5] A-385358
PRODUCTS SPECIFICATIONS [406228-55-5]
DESCRIPTION [406228-55-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 639.83 |
| Molecular Formula | C32H41N5O5S2 |
| SMILES | O=C(NS(=O)(C1=CC=C(N[C@@H](CSC2=CC=CC=C2)CCN(C)C)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCC(C)(C)CC4)C=C3 |
Summary
A-385358 is a selective inhibitor of Bcl-X L with K i s of 0.80 and 67 nM for Bcl-X L and Bcl-2 , respectively.
IC50 & Target
|
Bcl-xL 0.8 nM (Ki) |
Bcl-2 67 nM (Ki) |
In Vitro
A-385358 is a selective inhibitor of Bcl-X L with K i s of 0.80 and 67 nM for Bcl-X L and Bcl-2, respectively, in fluorescence polarization assays. Treatment of IL-3-deprived FL5.12/Bcl-X L cells for 24 hours with A-385358 results in cell killing with an EC 50 of 0.47±0.05 μM (n=68). This effect is accompanied by an increase in caspase-3 activity. Consistent with the greater affinity for the Bcl-X L versus Bcl-2 hydrophobic grooves, the EC 50 of A-385358 for IL-3-depleted FL5.12/Bcl-2 cells (1.9±0.1 μM; n=55) is 4-fold higher relative to the cytokine-deprived FL5.12/Bcl-X L cells. In addition, A-385358 is more effective at stimulating cytochrome c release from mitochondria isolated from FL5.12/Bcl-X L versus Bcl-2 cells [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
The combination of A-385358 given at 100 mg/kg/d plus the lower dose of paclitaxel produces a significant reduction in tumor growth (%T/C) compare with paclitaxel monotherapy. This combination also yields a >100% increase in time for tumors to reach 900 mm 3 (%ILS) compare with vehicle control. Maximal efficacy is observed during the dosing period for A-385358, with slow but steady increase in the tumor growth after termination of treatment. The combination of A-385358 at 75 mg/kg/d plus paclitaxel at 30 mg/kg/d is also well tolerated and inhibits tumor growth rate by nearly 80%. Significant effects on tumor growth relative to paclitaxel monotherapy are observed with doses as low as 50 mg/kg/d [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 50 mg/mL ( 78.15 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.5629 mL | 7.8146 mL | 15.6292 mL |
| 5 mM | 0.3126 mL | 1.5629 mL | 3.1258 mL |
| 10 mM | 0.1563 mL | 0.7815 mL | 1.5629 mL |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (3.91 mM); Clear solution