[CAS NO. 1258392-53-8] AZD5582
PRODUCTS SPECIFICATIONS [1258392-53-8]
DESCRIPTION [1258392-53-8]
Overview
| MDL | MFCD28411397 |
|---|---|
| Molecular Weight | 1015.29 |
| Molecular Formula | C58H78N8O8 |
| SMILES | CN[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 |
6 Publications Citing Use of MCE
Summary
IC50 & Target
|
cIAP1 15 nM (IC 50 ) |
cIAP2 21 nM (IC 50 ) |
XIAP 15 nM (IC 50 ) |
In Vitro
AZD5582 (20 nM; 48 hours) inhibits cell viability by cooperation with IFNγ or viral double-stranded RNA (dsRNA) in H1975 NSCLC cells
[2]
.
AZD5582 (20 nM; 17 or 25 hours) downregulates cIAP-1, activates RIPK1 (upstream regulator of caspase-8), and triggers the activation of extrinsic (caspase-8) and intrinsic (caspase-9) apoptosis pathways, causing the cleavage of caspase-3 and caspase-7
[2]
.
AZD5582 (20 nM; 48 hours) involves in apoptosis due to induction of cell death and active caspase-3/8 activities by AZD5582 and IFNγ co-treatment in HCC827 NSCLC cells
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [2]
| Cell Line: | H1975 NSCLC cell line |
| Concentration: | 20 nM |
| Incubation Time: | 48 hours |
| Result: | Cooperated with IFNγ or viral double-stranded RNA (dsRNA) to inhibit cell viability even cell death. |
Apoptosis Analysis [2]
| Cell Line: | HCC827 NSCLC cell line |
| Concentration: | 20 nM |
| Incubation Time: | 48 hours |
| Result: | Had an inhibitory effect on cell viability by cooperating with IFNγ. |
Western Blot Analysis [2]
| Cell Line: | H1975 NSCLC cell line |
| Concentration: | 20 nM |
| Incubation Time: | 17 or 25 hours |
| Result: | Down-regulated cIAP-1, activated RIPK1 (upstream regulator of caspase-8), triggered the cleavage (activation) of caspase-3,7,8 and 9. |
In Vivo
AZD5582 (intravenous injection; 0.1-3.0 mg/kg; once a week; 2 weeks) causes degradation of cIAP1 and caspase 3 cleavage in tumor cells, and after a two-week treatment, the tumors largely resolved; when the mice are given a medium dose (0.5 mg/kg) of AZD5582, cIAP1 degrades after administration, but it takes a while time to reach apoptosis-inducing effect [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | MDA-MB-231 xenograft-bearing mice [1] |
| Dosage: | 0.1 mg/kg, 0.5 mg/kg, 3.0 mg/kg |
| Administration: | Intravenous injection; once a week; 2 weeks |
| Result: | Resulted in cIAP1 degradation and caspase-3 cleavage within tumor cells and causes substantial tumor regressions following two weekly doses of 3.0 mg/kg |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
Solvent & Solubility
DMSO : ≥ 66.25 mg/mL ( 65.25 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 0.9849 mL | 4.9247 mL | 9.8494 mL |
| 5 mM | 0.1970 mL | 0.9849 mL | 1.9699 mL |
| 10 mM | 0.0985 mL | 0.4925 mL | 0.9849 mL |
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1.
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (2.46 mM); Clear solution
References
- [1] Hennessy EJ, et al. Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582). J Med Chem. 2013 Dec 27;56(24):9897-919.
- [2] Qin Hao, et al. IF-γ and Smac mimetics synergize to induce apoptosis of lung cancer cells in a TNFα-independent manner,Cancer Cell Int. 2018; 18: 84.