| Identification | Back Directory | [Name]
AZD-5582 | [CAS]
1258392-53-8 | [Synonyms]
CS-2673
AZD-5582
AZD5582;AZD-5582;AZD 5582
3,3'-[2,4-Hexadiyne-1,6-diylbis[oxy[(1S,2R)-2,3-dihydro-1H-indene-2,1-diyl]]]bis[N-methyl-L-alanyl-(2S)-2-cyclohexylglycyl-L-prolinamide]
L-Prolinamide, 3,3'-[2,4-hexadiyne-1,6-diylbis[oxy[(1S,2R)-2,3-dihydro-1H-indene-2,1-diyl]]]bis[N-methyl-L-alanyl-(2S)-2-cyclohexylglycyl-
(S,S,2S,2'S)-N,N'-((1S,1'S,2R,2'R)-(hexa-2,4-diyne-1,6-diylbis(oxy))bis(2,3-dihydro-1H-indene-2,1-diyl))bis(1-((S)-2-cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)pyrrolidine-2-carboxamide) | [Molecular Formula]
C58H78N8O8 | [MDL Number]
MFCD28411397 | [MOL File]
1258392-53-8.mol | [Molecular Weight]
1015.29 |
| Chemical Properties | Back Directory | [Boiling point ]
1207.3±65.0 °C(Predicted) | [density ]
1.26±0.1 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light, stored under nitrogen | [solubility ]
DMF: 30 mg/ml; DMSO: 15 mg/ml; Ethanol: 30 mg/ml | [form ]
A crystalline solid | [pka]
12.99±0.40(Predicted) | [color ]
White to yellow |
| Hazard Information | Back Directory | [Uses]
It is a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer. | [Biological Activity]
AZD5582 is a divalent AVPI motif-based Smac (DIABLO) mimetic (SMC) th at acts a potent apoptosis protein repe at (BIR) domain-targeting antagonist against inhibitor of apoptosis proteins (IAPs) cIAP1/2 (BIR3 IC50 = 15/21 nM against 2.5 nM AbuRPFK-5FAM) and XIAP (BIR2/3 IC50 = 21/15 nM). AZD5582 abolishes cellular XIAP-caspase-9 interaction (1 μM4 hrs)induces cIAP1/2 degradation (EC50 = 0.1 nM1 hr) and apoptosis (GI50 <60 pM48 hrs) in MDA-MB-231 breast cancer cultures. AZD5582 causes substantial tumor regression by inducing cIAP1 degradation and apoptosis in tumor cells in MDA-MB-231 xenograft-bearing mice in vivo (3.0 mg/kg/wk i.v.). | [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]. | 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 |
| [IC 50]
cIAP1: 15 nM (IC50); cIAP2: 21 nM (IC50); XIAP: 15 nM (IC50) |
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