Talazoparib (BMN 673)
目录号：S7048 别名： LT-673
Molecular Weight(MW): 380.35
Talazoparib (BMN 673)是一种新型的PARP抑制剂，无细胞试验中对PARP1的IC50为0.57 nM。它也是有效的PARP-2抑制剂，但不抑制PARG，对PTEN突变型高度敏感。Phase 3。
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客户使用该产品的4个实验数据：
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Western blot assessment of effects on PAR, PARP, and dsDNA breaks mediated by IMMU-132 plus PARPi in TNBC tumor lines. Cells were plated overnight in 6-well plates before the addition of chemotherapeutics. After a 24-hour incubation, cells were harvested and cell lysates resolved and transferred for Western analysis as described in Materials and Methods. PAR and FL-PARP levels were determined on the same gel. Assessment of dsDNA breaks (p-H2A.X) was calculated as ratios relative to untreated control (Unt) normalized to b-actin protein loading control (Dp-H2A.X). B, HCC1806 cells exposed to rucaparib (Ruc) and IMMU-132 or to (C) talazoparib (Tala) and IMMU-132.
Clin Cancer Res, 2017, 23(13):3405-3415. Talazoparib (BMN 673) purchased from Selleck.
PARP inhibition prevents adhesion to and migration of monocytes across BMVEC monolayers preserving the barrier. Primary human monocytes were treated for 24 h with PARPi (AIQ, olaparib, EB47, talazoparib), calcein-labeled, washed, and then added to BMVEC monolayers (untreated or treated for 24 h with TNFα). Treatments were removed prior to the addition of monocytes. Adhesion to (a) and migration of (b) monocytes across blood-brain barrier models were measured and are presented as fold difference compared to TNFα-only control (mean ± SEM) for each treatment from at least quadruplicate determinations, which was assigned a value of 1 (7600 relative fluorescent units for adhesion or equivalent to 37 migrated cells). *P < 0.05, **P < 0.01 indicate significance vs. non-treated. TEER, an indicator of barrier integrity, was continuously measured in BMVEC monolayers treated with or without TNFα following the addition of primary human monocytes that had been treated with PARPi.
J Neuroinflammation, 2016, 13(1):254.. Talazoparib (BMN 673) purchased from Selleck.
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BT-549 cells reconstituted with Vet, WT, 336* or PTEN WT HP1aKD were treated with BMN673. Relative cell viability was determined by MTT assay. The results were presented as mean of 3 independent experiments. Error bars indicate s.d.
Cell Cycle, 2015, 14(14): 2323-32. Talazoparib (BMN 673) purchased from Selleck.
We treated the FA defective and control lung cancer cell lines H1299D2-down/H1299E and A549D2 down/A549E with BMN673 (0.5 µM). MTT assay was used for the cell viability analysis and an averaged absorbance was recorded 24, 48 and 72 h post treatment.
Front Oncol, 2014, 4: 368. Talazoparib (BMN 673) purchased from Selleck.
产品安全说明书
PARP抑制剂选择性比较
生物活性
| 产品描述 | Talazoparib (BMN 673)是一种新型的PARP抑制剂，无细胞试验中对PARP1的IC50为0.57 nM。它也是有效的PARP-2抑制剂，但不抑制PARG，对PTEN突变型高度敏感。Phase 3。 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 特性 | 到目前为止报道的最有效的选择性PARP抑制剂。 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 靶点 |
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| 体外研究 |
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。BMN 673作用于BRCA-1突变 (MX-1,IC50 = 0.3 nM) 和BRCA-2 突变的细胞(Capan-1,IC50 = 5 nM)，具有单药细胞毒性。相反, BMN-673 作用于MRC-5正常人类成纤维细胞和其他含野生型BRCA-1 和 BRCA-2基因的肿瘤细胞系，IC50为90 nM到1.9 μM。[1] BMN 673 作用于培养的人类癌细胞，也显著增强Temozolomide 和 SN-38的细胞毒性效果。[2] |
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| Cell Data |
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| 体内研究 | 在大鼠的药代动力学研究中，BMN673每天单独给药，具有>50％口服生物有效性和药代动力学特性。在MX-1移植瘤肿瘤模型研究中, BMN 673每天口服给药，显著增强细胞毒性疗法的抗肿瘤效果，这种作用具有剂量依赖性。[2] |
推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)
| 动物实验： |
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溶解度 (25°C)
| 体外 | DMSO | 38 mg/mL warmed (99.9 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble |
* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。
化学数据
| 分子量 | 380.35 |
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| 化学式 |
C19H14F2N6O
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| CAS号 | 1207456-01-6 |
| 稳定性 | powder |
| in solvent | |
| 别名 | LT-673 |
计算器
摩尔浓度计算器
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。
稀释计算器
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
分子量计算器
通过输入化合物的化学式来计算其分子量：
注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2
摩尔浓度计算器
临床试验信息
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT03426254 | Enrolling by invitation | Advanced or Recurrent Solid Tumors|Breast Neoplasm | Center Trials & Treatment|BioGene Pharmaceutical | February 8 2018 | Phase 1 |
| NCT02997163 | Recruiting | Advanced Solid Tumors | Pfizer|Medivation Inc. | February 8 2017 | Phase 1 |
| NCT02921919 | Recruiting | Cancer | Pfizer|Medivation Inc. | November 8 2016 | Phase 2 |
| NCT03377556 | Recruiting | ATM Gene Mutation|ATR Gene Mutation|BARD1 Gene Mutation|BRCA1 Gene Mutation|BRCA2 Gene Mutation|BRIP1 Gene Mutation|CHEK1 Gene Mutation|CHEK2 Gene Mutation|FANCA Gene Mutation|FANCC Gene Mutation|FANCD2 Gene Mutation|FANCF Gene Mutation|FANCM Gene Mutation|NBN Gene Mutation|PALB2 Gene Mutation|RAD51 Gene Mutation|RAD51B Gene Mutation|RAD54L Gene Mutation|Recurrent Squamous Cell Lung Carcinoma|RPA1 Gene Mutation|Stage IV Squamous Cell Lung Carcinoma AJCC v7 | Southwest Oncology Group|National Cancer Institute (NCI) | February 7 2017 | Phase 2 |
| NCT03077607 | Completed | Advanced Solid Tumors | Pfizer|Medivation Inc. | November 7 2016 | Phase 1 |
| NCT03148795 | Recruiting | Prostate Cancer | Pfizer|Medivation Inc. | July 4 2017 | Phase 2 |
技术支持
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常见问题及建议解决方法
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问题 1：
Which solvent do you recommend to dilute the inhibitor for in vivo study in mice?
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回答：
BMN673 (S7048) can be dissolved in vehicle (10% DMAc, 6% Solutol, and 84% PBS) according to the paper: http://clincancerres.aacrjournals.org/content/19/18/5003.full. Quote from Method and Material section "Xenograft experiments: BMN 673 (various doses as indicated), or vehicle (10% DMAc, 6% Solutol, and 84% PBS) was administered by oral gavage"
