AZD5582 - 98%, high purity , CAS No.1258392-53-8, Antagonist of baculoviral IAP repeat containing 2;Antagonist of baculoviral IAP repeat containing 3;Antagonist of X-linked inhibitor of apoptosis

Item Number
A413749
Grouped product items
SKUSizeAvailabilityPrice Qty
A413749-5mg
5mg
In stock
$179.90
A413749-10mg
10mg
In stock
$279.90
A413749-25mg
25mg
In stock
$356.90

XIAP Selective Inhibitors | Antagonists

Basic Description

Specifications & PurityMoligand™, ≥98%
Biochemical and Physiological MechanismsAZD5582, a novel small-molecule IAP inhibitor, binds potently to the BIR3 domains of cIAP1, cIAP2, and XIAP with IC50 values of 15, 21, and 15
Storage TempStore at -20°C,Argon charged
Shipped InIce chest + Ice pads
GradeMoligand™
Action TypeANTAGONIST
Mechanism of actionAntagonist of baculoviral IAP repeat containing 2;Antagonist of baculoviral IAP repeat containing 3;Antagonist of X-linked inhibitor of apoptosis
Product Description

Information

AZD5582, a novel small-molecule IAP inhibitor, binds potently to the BIR3 domains ofcIAP1,cIAP2, andXIAPwithIC50values of 15, 21, and 15


Targets

cIAP1 (Cell-free assay); XIAP (Cell-free assay); cIAP2 (Cell-free assay) 15 nM; 15 nM; 21 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 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.


Cell Research(from reference)

Cell lines:The human pancreatic cancer cell lines including BxPC-3, Miapaca-2, Panc-1, Panc0813, PL45, Capan-1, Capan-2 and AsPC-1 

Concentrations:0, 0.01, 0.1, 0.5 μM 

Incubation Time:72 h 


Product Describtion:

AZD5582 is an antagonist of the inhibitor of apoptosis proteins (IAPs), which binds to the BIR3 domains cIAP1, cIAP2, and XIAP with IC50s of 15, 21, and 15 nM, respectively. AZD5582 induces apoptosis


Product Properties

ALogP5.317
HBD Count6
Rotatable Bond21

Associated Targets(Human)

BIRC2 Tchem Baculoviral IAP repeat-containing protein 2 (3 Activities)
Activity TypeActivity Value -log(M)Mechanism of ActionActivity ReferencePublications (PubMed IDs)
BIRC3 Tchem Baculoviral IAP repeat-containing protein 3 (2 Activities)
Activity TypeActivity Value -log(M)Mechanism of ActionActivity ReferencePublications (PubMed IDs)
XIAP Tchem E3 ubiquitin-protein ligase XIAP (3 Activities)
Activity TypeActivity Value -log(M)Mechanism of ActionActivity ReferencePublications (PubMed IDs)
ABL1 Tclin Tyrosine-protein kinase ABL (18331 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GSK3B Tclin Glycogen synthase kinase-3 beta (11785 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CSNK1D Tchem Casein kinase I delta (4546 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CDK2 Tchem Cyclin-dependent kinase 2 (9050 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
AURKA Tchem Serine/threonine-protein kinase Aurora-A (10240 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
XIAP Tchem Inhibitor of apoptosis protein 3 (3673 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Caco-2 (12174 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
U2OS (164939 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HepG2 (196354 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MDA-MB-231 (73002 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BT-549 (31254 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BIRC3 Tchem Baculoviral IAP repeat-containing protein 3 (320 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BIRC2 Tchem Baculoviral IAP repeat-containing protein 2 (984 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BRD4 Tchem Bromodomain-containing protein 4 (13122 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TRIM24 Tchem Transcription intermediary factor 1-alpha (2087 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BRPF1 Tchem Peregrin (2217 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HEK-293T (167025 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Mapk1 MAP kinase ERK2 (650 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Hdac6 Histone deacetylase 6 (222 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Fgfr3 Fibroblast growth factor receptor 3 (21 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
rep Replicase polyprotein 1ab (378 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Names and Identifiers

Pubchem Sid488201441
Pubchem Sid Urlhttps://pubchem.ncbi.nlm.nih.gov/substance/488201441
IUPAC Name (2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(1S,2R)-2-[6-[[(1S,2R)-1-[[(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-2,3-dihydro-1H-inden-2-yl]oxy]hexa-2,4-diynoxy]-2,3-dihydro-1H-inden-1-yl]pyrrolidine-2-carboxamide
INCHI InChI=1S/C58H78N8O8/c1-37(59-3)53(67)61-49(39-21-9-7-10-22-39)57(71)65-31-19-29-45(65)55(69)63-51-43-27-15-13-25-41(43)35-47(51)73-33-17-5-6-18-34-74-48-36-42-26-14-16-28-44(42)52(48)64-56(70)46-30-20-32-66(46)58(72)50(40-23-11-8-12-24-40)62-54(68)38(2)60-4/h13-16,25-28,37-40,45-52,59-60H,7-12,19-24,29-36H2,1-4H3,(H,61,67)(H,62,68)(H,63,69)(H,64,70)/t37-,38-,45-,46-,47+,48+,49-,50-,51-,52-/m0/s1
InChi Key WLMCRYCCYXHPQF-ZVMUOSSASA-N
Canonical SMILES CC(C(=O)NC(C1CCCCC1)C(=O)N2CCCC2C(=O)NC3C(CC4=CC=CC=C34)OCC#CC#CCOC5CC6=CC=CC=C6C5NC(=O)C7CCCN7C(=O)C(C8CCCCC8)NC(=O)C(C)NC)NC
Isomeric SMILES C[C@@H](C(=O)N[C@@H](C1CCCCC1)C(=O)N2CCC[C@H]2C(=O)N[C@@H]3[C@@H](CC4=CC=CC=C34)OCC#CC#CCO[C@@H]5CC6=CC=CC=C6[C@@H]5NC(=O)[C@@H]7CCCN7C(=O)[C@H](C8CCCCC8)NC(=O)[C@H](C)NC)NC
PubChem CID 49847690
MeSH Entry Terms AZD5582;N,N'-(2,2'-(hexa-2,4-diyne-1,6-diylbis(oxy))bis(2,3-dihydro-1H-indene-2,1-diyl))bis(1-(2-cyclohexyl-2-(2-(methylamino)propanamido)acetyl)pyrrolidine-2-carboxamide)
Molecular Weight 1015.29

Certificates

Certificate of Analysis(COA)

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6 results found

Lot NumberCertificate TypeDateItem
D2321588Certificate of AnalysisMar 22, 2023 A413749
D2321592Certificate of AnalysisMar 22, 2023 A413749
D2321593Certificate of AnalysisMar 22, 2023 A413749
D2321594Certificate of AnalysisMar 22, 2023 A413749
D2321595Certificate of AnalysisMar 22, 2023 A413749
D2321596Certificate of AnalysisMar 22, 2023 A413749

Chemical and Physical Properties

SolubilitySolubility (25°C) In vitro Water: 100 mg/mL (98.49 mM);    
Sensitivitylight sensitive
Water(mg / mL) Max Solubility100
Water(mM) Max Solubility98.49402634

Related Documents

References

1. Hennessy EJ, Adam A, Aquila BM, Castriotta LM, Cook D, Hattersley M, Hird AW, Huntington C, Kamhi VM, Laing NM et al..  (2013)  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,  56  (24): (9897-919).  [PMID:24320998] [10.1021/op500134e]

Solution Calculators