AZD 5582

生物活性靶点体外研究体内研究 AZD 5582 试剂级价格

AZD 5582

CAS号:1258392-53-8
英文名:AZD-5582
中文名:AZD 5582
CBNumber:CB52731019
分子式:C58H78N8O8
分子量:1015.29
MOL File:1258392-53-8.mol

AZD 5582化学性质

沸点 :1207.3±65.0 °C(Predicted)
密度 :1.26±0.1 g/cm3(Predicted)
储存条件 :4°C, protect from light, stored under nitrogen
溶解度 :DMF: 30 mg/ml; DMSO: 15 mg/ml; Ethanol: 30 mg/ml
形态 :A crystalline solid
酸度系数(pKa) :12.99±0.40(Predicted)

AZD 5582性质、用途与生产工艺

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 )

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.

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