祝贺AbMole成为ChemBridge中国区唯一官方指定合作伙伴!

BMN673

目录号 M1732 所有产品仅供科研使用,严禁用于人或动物的治疗等任何其他用途,不为任何个人提供产品和服务  


BMN 673是一种新型的PARP抑制剂,IC50为0.58 nM,也有效抑制PARP-2,但不抑制PARG,对PTEN突变型高度敏感。

BMN673结构式

别名:BMN-673, LT-673,Talazoparib

包装 价格 库存状态
10mM*1mL 原价 ¥ 1350
促销价 ¥ 1282.5
中国库存现货
5mg 原价 ¥ 1440
促销价 ¥ 1368
中国库存现货
10mg 原价 ¥ 2160
促销价 ¥ 2052
中国库存现货
50mg 原价 ¥ 5400
促销价 ¥ 5130
中国库存现货
100mg 原价 ¥ 8640
促销价 ¥ 8208
中国库存现货
其他规格数量报价?

质量控制及产品安全说明书
生物活性

BMN 673是一种新型的PARP抑制剂,IC50为0.58 nM,也有效抑制PARP-2,但不抑制PARG,对PTEN突变型高度敏感。BMN-673 选择性与PARP 结合,且抑制PARP-介导的通过碱基切除修复途径的单链DNA断裂的修复。增强了DNA链断裂的积累,促进基因组不稳定性,并最终导致细胞凋亡。BMN 673选择性杀死BRCA-1或BRCA-2突变的癌细胞。

实验操作 来自于公开的文献,仅供相同实验参考(如实验材料、目的不同,请参考其他文献)
细胞实验
细胞系 Capan-1 and MIA PaCa-2
方法 Real-time cell analysis (xCELLigence)
浓度
处理时间 48 h
动物实验
动物模型 Patient-derived xenograft (PDX) model
配制 Solubilized in DMSO and diluted with PBS containing 10% dimethylacetamide (Sigma-Aldrich) and 6% Solutol (Sigma-Aldrich).
剂量 0.33 mg/kg, 0.05 cc, once daily
给药处理 oral gavage
不同实验动物依据体表面积的等效剂量转换表(数据来源于FDA指南)
小鼠 大鼠 豚鼠 仓鼠
重量 (kg) 0.02 0.15 1.8 0.4 0.08 10
体表面积 (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km 系数 3 6 12 8 5 20
动物 A (mg/kg) = 动物 B (mg/kg) ×  动物 B的Km系数
动物 A的Km系数

例如,依据体表面积折算法,将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量,需要将22.4 mg/kg 乘以小鼠的Km系数(3),再除以大鼠的Km系数(6),得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。

化学数据
分子量 380.35
分子式 C19H14F2N6O
CAS号 1207456-01-6
纯度 99.86%
溶解性(25°C) DMSO 30 mg/mL
储存和运输条件 固体粉末: -20°C 冷藏长期储存
常温运输及临时存放
储备液配制

以下数据基于产品分子量,对于特殊产品,请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 2.6292 mL 13.1458 mL 26.2916 mL
5 mM 0.5258 mL 2.6292 mL 5.2583 mL
10 mM 0.2629 mL 1.3146 mL 2.6292 mL
使用AbMole产品发表的文献
客户产品验证及相关生物数据
数据来源 Cancer Cell (2016). Figure 4. BMN 673 (Abmole Bioscience)
方法
细胞系 TNBC cells
浓度 1–5 nM
处理时间 72 h
实验结果 As expected, TNBC cells mutant for BRCA1 (SUM149PT) are sensitive to talazoparib (10 nM BMN 673) alone, but these cells are even more sensitive to a combination of talazoparib (1 and 10 nM) and AZA (150 nM).
数据来源 Cancer Cell (2016). Figure 3. BMN 673 (Abmole Bioscience)
方法 MTS assay
细胞系 MDA-MB-231 cells, MOLM14 cells
浓度 2.5–20 nM
处理时间 72 h
实验结果 Significant decrease in survival was also observed with combination drug treatments (AZA and BMN 673 or DAC and BMN 673) compared with either drug alone (Figures 3A–3D, middle and lower panels).
数据来源 Cancer Cell (2016). Figure 2. BMN 673 (Abmole Bioscience)
方法
细胞系 MDA-MB-231 cells, MOLM14 cells
浓度 10 nM
处理时间 72 h
实验结果 Also, in MOLM14 AML cells, combination dosing with DAC (5 nM) and BMN 673 (5 nM) induces increases in gH2AX foci, as compared with single-drug treatments (Figure 2G). In a key association with the above data, both MOLM14 AML and MDA-MB-231 TNBC cells treated with the combination of the two drugs exhibit synergistic cytotoxicity, as assessed by the CalcuSyn model.
数据来源 Cancer Cell (2016). Figure 1. BMN 673 (Abmole Bioscience)
方法
细胞系 MOLM14 cells
浓度 1, 2.5, and 5 nM
处理时间 72 h
实验结果 In our present study, talazoparib (BMN 673) at very low nanomolar concentrations (1, 2.5, or 5 nM) also traps PARP1 in chromatin extracts (Figure 1C) to thesame extent as the weaker PARPi ABT888 at much higher concentrations (500 nM) (Figure S2A).
数据来源 McGill University (2015). Figure S2.BMN 673 (Abmole Biosciences, Hong Kong, China).
方法 Cells were plated in 6-well plates at 2x104 cells/well and treated 24 h later with veliparib, cisplatin or BMN 673.
细胞系 Capan-1 (HTB-79), MIA PaCa-2 (CRL-1420) and PANC-1 (CRL-1469)
浓度
处理时间 24 h
实验结果 The cytotoxicity fold-differences and IC50 values of cisplatin and BMN 673 appeared comparable, suggesting that the efficacy of cisplatin and BMN 673 may be similar and that BMN 673 may be a less toxic alternative to cisplatin21,22
数据来源 McGill University (2015). Figure 5.BMN 673 (Abmole Biosciences, Hong Kong, China).
方法 Cells were plated in 6-well plates at 2x104 cells/well and treated 24 h later with veliparib, cisplatin or BMN 673.
细胞系 Capan-1 (HTB-79), MIA PaCa-2 (CRL-1420) and PANC-1 (CRL-1469)
浓度
处理时间 24 h
实验结果 These data suggest that the GI effects observed in the cisplatin and BMN 673 treatment arms are due to the anti-proliferative effects of these agents, and that these two drugs have equivalent anti-proliferative effects on a PDAC arising from germline BRCA2 mutation carriers.
数据来源 McGill University (2015). Figure 4.BMN 673 (Abmole Biosciences, Hong Kong, China).
方法 Cisplatin and BMN 673 were solubilized in DMSO and diluted with PBS containing 10% dimethylacetamide and 6% Solutol.
细胞系 Capan-1 (HTB-79), MIA PaCa-2 (CRL-1420) and PANC-1 (CRL-1469)
浓度 0.33 mg/kg,
处理时间
实验结果 Figure 4A demonstrates marked growth inhibition with cisplatin and BMN 673 treatments. End-point tumor volumes correlated with the growth curve observations.In support of our in vitro findings, treatment with BMN 673 (10 tumors) also resulted in significant GI compared with vehicle-treated controls (8 tumors)
数据来源 McGill University (2015). Figure 3.BMN 673 (Abmole Biosciences, Hong Kong, China).
方法 Cisplatin and BMN 673 were solubilized in DMSO and diluted with PBS containing 10% dimethylacetamide and 6% Solutol.
细胞系 Capan-1 (HTB-79), MIA PaCa-2 (CRL-1420) and PANC-1 (CRL-1469)
浓度 0.33 mg/kg,
处理时间
实验结果 This provided us with additional cell lines harboring intermediate HDR activity with which to further characterize the in vitro effectiveness of BMN 673 compared to veliparib and cisplatin prior to undertaking a BMN 673 preclinical PDX trial.
数据来源 Cell Reports (2015). Figure 4. BMN-673 was purchased from Abmole (BMN673, 1207456-01-6)
方法 Orthotopic EWS Xenograft Model
细胞系 EWS cell lines
浓度 0.1 mg/kg
处理时间 12–18 weeks
实验结果 "The following percentages of each group showed CR: 15% (3/20) in the veliparib + IRN + TMZ (50%) group, 71% (12/17) in the olaparib + IRN + TMZ (50%) group, and 88% (14/16) in the BMN-673 (80%) + IRN + TMZ (30%) group. The Xenogen data correlated with tumor burden and histopathology."
数据来源 Cell Reports (2015). Figure 4. BMN-673 was purchased from Abmole (BMN673, 1207456-01-6)
方法 Orthotopic EWS Xenograft Model
细胞系 EWS cell lines
浓度 0.1 mg/kg
处理时间 12–18 weeks
实验结果 "The tolerability of TMZ was even less in combination with BMN-673.The BMN- 673 (80%) + IRN + TMZ (30%) group had four mice with CR."
数据来源 Cell Reports (2015). Figure 2. BMN-673 was purchased from Abmole (BMN673, 1207456-01-6)
方法 Cell Titer Glo (Promega, G7570)
细胞系 EW8, ES6, SAOS2 cell lines
浓度 0, 1, 2.5, 5, 10, 20, 50, or 100 µM
处理时间 72hr or 144hr
实验结果 "At 72 hr of exposure, EW-8, ES-8, and ES-1 cells were sensitive to BMN-673 and olaparib, and, at 144 hr, all EWS cell lines except ES-6 were sensitive to all three PARPis."
数据来源 Cancer Letters(2015). Figure 5. BMN 673 (Abmole Biosciences, Hong Kong, China)
方法 Immunohistochemistry H&E staining
细胞系
浓度
处理时间
实验结果 The GI effects observed in the cisplatin and BMN 673 treatment arms are due to both anti-proliferative and proapoptotic effects of these agents on a PDAC arising from germline BRCA2 mutation carriers.
数据来源 Cancer Letters(2015). Figure 4. BMN 673 (Abmole Biosciences, Hong Kong, China)
方法 Preclinical PDX trial
细胞系
浓度 0.33 mg/kg, 0.05 cc, once daily
处理时间 70 days
实验结果 Treatment with BMN 673 (10 tumors) also resulted in significant GI compared with vehicle treated controls (8 tumors) (195.05 mm3 ± 95.21 mm3 (SD) versus 520.55 mm3 ± 62.68 mm3 (SD); p = 0.0006); cisplatin and BMN 673 have similar efficacies in this BRCA2 associated PDAC.
数据来源 Cancer Letters(2015). Figure 4. BMN 673 (Abmole Biosciences, Hong Kong, China)
方法 long-term colony formation assays
细胞系 PANC-1 BRCA2-knockdown cell lines
浓度 0.3125; 0.625; 1.25; 2.5; 5μM
处理时间 10 days
实验结果 The IC50 values with BMN 673 were 0.57 μM ± 0.16 μM (p < 0.0001) and 0.53 μM ± 0.13 μM(p < 0.0001) in the PANC-1_shRNA 2 [BRCA2] and PANC-1_shRNA 3 [BRCA2] cell lines compared to 1.22 μM ± 0.25 μM in the control cell line. BMN 673 is a more effective PARPi for BRCA2-associated PDAC compared to the earlier-generation PARPis such as veliparib, and that BMN 673, rather than veliparib, should be selected for our preclinical PDX trial evaluation.
数据来源 Cancer Letters(2015). Figure 2. BMN 673 (Abmole Biosciences, Hong Kong, China)
方法 Real-time cell analysis (xCELLigence)
细胞系 Capan-1 and MIA PaCa-2
浓度 unnoted
处理时间 48 hours
实验结果 Mean IC50 values were 11.4 mM ± 1.4 mM versus 12.7 mM ± 3.6 mM for gemcitabine (NS), 38.3 μM ± 7.3 μM versus 10.2 ± 1.5 μM (p = 0.0150) for cisplatin, and 58.23 ± 8.1 μM versus 16.0 ± 5.4 μM (p = 0.0105) for BMN 673 in MIA PaCa-2 versus Capan-1 cells, respectively. The efficacy of cisplatin and BMN 673 may be similar and that BMN 673 may be a less toxic alternative to cisplatin.
参考文献

Structure and preclinical characterization of BMN 673, a potent and orally active PARP inhibitor as an anticancer agent.
Yuqiao et al. Mol Cancer Ther. 2011 Nov;10(11 Suppl).

Correlation of pharmacokinetics (PK), pharmacodynamics (PD) and in vivo antitumor activity of BMN 673 in preclinical models.
Ying et al. Mol Cancer Ther. 2011 Nov;10(11 Suppl).

  获取最新目录册
Abmole10周年目录册
其他相关的PARP产品
BRCA1-IN-2

BRCA1-IN-2是一种细胞渗透性的BRCA1蛋白-蛋白相互作用(PPI)抑制剂,其IC50值为0.31 μM,Kd值为0.3 μM。

RBN-2397

RBN-2397是一种有效的,具有口服活性的NAD+竞争性PARP7抑制剂,IC50值小于3 nM。

Pamiparib

Pamiparib (BGB-290)是一种有效的PARP1和PARP2选择性抑制剂,对PARP1和PARP2的IC50值分别为0.9 nM和0.5 nM。

BGP-15 2HCl

BGP-15是一种新型的聚(ADP-核糖)聚合酶 PARP 抑制剂,其IC50和Ki值分别为120 μM和57 μM。

Benzamide

Benzamide是一种PARP的抑制剂,其IC50值为3.3 μM。





关键词:BMN673, BMN-673, LT-673,Talazoparib, BMN673供应商, PARP抑制剂, 购买BMN673, BMN673结构式

联系我们

Copyright © 2010-2020 AbMole版权所有 沪ICP备16047849号

沪公网安备 31011502012228号

产品仅供实验室人员研究使用,不对个人出售。