AZD5582

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AZD5582 是一种二聚体 Smac 模拟物，有效的 IAP 拮抗剂。

AZD5582 is a dimeric Smac mimetic, potent IAP antagonist that binds potently to the BIR3 domains of cIAP1, cIAP2 and XIAP with IC50 of 15, 21and 15 nM, respectively; causes cIAP1 degradation and induces apoptosis in the MDA-MB-231 breast cancer cell line at subnanomolar concentrations in vitro; induces cIAP1 degradation and caspase-3 cleavage within tumor cells and causes substantial tumor regressions in MDA-MB-231 xenograft-bearing mice.

AZD5582 (20 nM; 48 hours) inhibits cell viability by cooperation with IFNγ or viral double-stranded RNA (dsRNA) in H1975 NSCLC cells.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.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. Cell Viability Assay 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 Cell Line:HCC827 NSCLC cell line Concentration:20 nM Incubation Time:48 hoursResult:Had an inhibitory effect on cell viability by cooperating with IFNγ.Western Blot Analysis 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.

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. Animal Model:MDA-MB-231 xenograft-bearing mice 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

AZD-5582

Apoptosis

IAP

IAP

Cancer

——

1258392-53-8

1015.289

C58H78N8O8

>98% (HPLC)

DMSO: ≥ 66.25 mg/mL

CN[C@@H](C)C(N[C@@H](C1CCCCC1)C(N2[C@H](C(N[C@H]3C(C=CC=C4)=C4C[C@H]3OCC#CC#CCO[C@@H]5CC6=C(C=CC=C6)[C@@H]5NC([C@H](CCC7)N7C([C@H](C8CCCCC8)NC([C@H](C)NC)=O)=O)=O)=O)CCC2)=O)=O.

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-

(-20℃)

With Ice Pack

≥ 2 years