[CAS NO. 1258392-53-8]  AZD5582

Ships within Stock Price Qty Total
$0.00
$0.00
Please click "REQUEST A QUOTE" button if you need other sizes or custom synthesis
request a quote
If there is no stock, or you need other sizes or custom synthesis, please:

PRODUCTS SPECIFICATIONS [1258392-53-8]

Catelog
SLK-S7362
Brand
Selleck
CAS
1258392-53-8

DESCRIPTION [1258392-53-8]

Overview

MDLMFCD28411397
Molecular Weight1015.29
Molecular FormulaC58H78N8O8
SMILESCN[C@@H](C)C(N[C@H](C(N1[C@H](C(N[C@H]2C3=CC=CC=C3C[C@H]2OCC#CC#CCO[C@H]4[C@@H](NC([C@@H]5CCCN5C([C@@H](NC([C@H](C)NC)=O)C6CCCCC6)=O)=O)C(C=CC=C7)=C7C4)=O)CCC1)=O)C8CCCCC8)=O

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

1 mg5 mg10 mg
1 mM0.9849 mL4.9247 mL9.8494 mL
5 mM0.1970 mL0.9849 mL1.9699 mL
10 mM0.0985 mL0.4925 mL0.9849 mL
50 mM0.0197 mL0.0985 mL0.1970 mL

Description

AZD5582, a novel small-molecule IAP inhibitor, binds potently to the BIR3 domains of , , and with values of 15, 21, and 15

Targets

cIAP1 [1]
(Cell-free assay)
XIAP [1]
(Cell-free assay)
cIAP2 [1]
(Cell-free assay)
15 nM15 nM21 nM

In vitro

Human pancreatic cancer cells display different sensitivities to the synthetic IAP antagonist, AZD5582. Treating human pancreatic cancer cells with AZD5582 differentially induces apoptosis, dependent on the expression of p-Akt and p-XIAP. It targets cIAP1 to induce TNF-α-induced apoptosis. AZD5582 induces a decrease of Mcl-1 protein, a member of the Bcl-2 family, but not that of Bcl-2 and Bcl-xL. HNSCC (head and neck squamous cell carcinoma) cell lines SCC25, Cal27, and FaDu show a dose-dependent cytotoxic effect after treatment with AZD5582.

In vivo

After AZD5582 treatment, tumor growth and weight decrease, whereas cleaved caspase 3 expression increases in Panc-1-derived xenograft model. When administered intravenously to MDA-MB-231 xenograft-bearing mice, AZD5582 results in cIAP1 degradation and caspase-3 cleavage within tumor cells and causes substantial tumor regressions following two weekly doses of 3.0 mg/kg. Following a modest 0.5 mg/kg intravenous bolus dose of AZD5582 in mice, unbound plasma levels remain above the concentrations at which apoptosis induction and cell death are observed in MDA-MB-231 cells over the course of several hours. Although cIAP1 degradation happens very quickly upon exposure to AZD5582 in vivo, apoptosis induction (as measured by the amount of cleaved caspase-3) takes longer to reach a maximal effect. A single agent AZD5582 does not exhibit broad-based cytotoxicity but instead should be employed in selected tumor settings expected to be sensitive to IAP inhibitors or in rational combinations with other targeted therapies. The dihydrochloride salt of AZD5582 has sufficient aqueous solubility (>7 mg/mL at pH 4−6) to enable formulation for intravenous administration at the projected efficacious doses. With respect to chemical stability, AZD5582 is found to be photostable and hydrolytically stable between pH 4−6, although some amide hydrolysis is observed under strongly acidic (pH < 1) and basic (pH > 8) conditions. In addition, the compound is stable in the plasma of multiple species, with no compound degradation observed after several hours under physiological conditions.