AZD 5582
中文名称:
AZD 5582
中文同义词:
二聚化SMAC MIMETICS,IAPS抑制剂;(2S,2S)-1,1-((S,2S,2S)-2,2-(((1S,1S,2R,2R)-(己-2,4-二炔-1,6-二基双(氧))双(2,3-二氢-1H-茚-2,1-二基))双(环己烷-3,1-二基))双(2-((S)-2-(甲胺基)丙胺基)乙酰基)双(吡咯烷-2-甲酰胺)
英文名称:
AZD-5582
英文同义词:
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];AZD5582;AZD-5582;AZD 5582;CS-2673;(S,S,2S,2S)-N,N-((1S,1S,2R,2R)-(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);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-
CAS号:
1258392-53-8
分子式:
C58H78N8O8
分子量:
1015.29
EINECS号:
相关类别:
细胞生物学试剂;抑制剂
Mol文件:
1258392-53-8.mol
沸点
1207.3±65.0 °C(Predicted)
密度
1.26±0.1 g/cm3(Predicted)
酸度系数(pKa)
12.99±0.40(Predicted)
生物活性
AZD5582 是 IAP 拮抗剂，可以有效与 cIAP1，cIAP2 和 XIAP 的 BIR3 结构域结合, IC50 值分别为 15，21，15 nM。AZD5582 诱导凋亡 (apoptosis)。
靶点
cIAP1
15 nM (IC 50 )
cIAP2
21 nM (IC 50 )
XIAP
15 nM (IC 50 )
cIAP1
15 nM (IC 50 )
cIAP2
21 nM (IC 50 )
体外研究
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 hours
Result: 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.
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.
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.
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.
体内研究
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
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
