Talazoparib (BMN 673)
别名: LT-673
Talazoparib (BMN 673, LT-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。
Talazoparib (BMN 673) Chemical Structure
CAS: 1207456-01-6
产品质控
批次：
纯度：
99.84%
99.84
Talazoparib (BMN 673)相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| BR5FVB1-Akt | Apoptosis Assay | 0.1-100 nM | 72 h | induces apoptosis | 26047697 |
| BR5FVB1-Akt | Growth Inhibition Assay | 0.1-100 nM | 24/48/72 h | inhibits cell proliferation dose dependently | 26047697 |
| LoVo | Cytotoxicity assay | 0.4 uM | 5 days | GI50 = 0.004 μM | 26652717 |
| MX1 | Function assay | 1 mg/kg | 2 ,8 and 24 hrs | Decrease in PAR level in athymic nu/nu mouse xenografted with human MX1 cells at 1 mg/kg, po administered as single dose measured after 2 ,8 and 24 hrs by ELISA | 26652717 |
| MX1 | Antitumor assay | 0.33 mg/kg | 28 days | Antitumor activity against BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse at 0.33 mg/kg, po qd administered for 28 days | 26652717 |
| MX1 | Antitumor assay | 0.165 mg/kg | 28 days | Antitumor activity against BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse assessed as tumor growth inhibition at 0.165 mg/kg, po administered twice a day for 28 days | 26652717 |
| Capan1 | Function assay | 0.1 uM | 4 hrs | Inhibition of PARP1 in BRCA2 deficient human Capan1 cells assessed as increase in PARP1-DNA trapping at 0.1 uM after 4 hrs by Western blot analysis | 28692916 |
| MDA-MB-436 | Function assay | 1 uM | 4 hrs | Inhibition of PARP1 in BRCA1 deficient human MDA-MB-436 cells assessed as increase in PARP1-DNA trapping at 1 uM after 4 hrs by Western blot analysis | 28692916 |
| MX1 | Function assay | 0.33 mg/kg | Potentiation of carboplatin-induced tumor growth inhibition of BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse at 0.33 mg/kg po and animals were treated with carboplatin at 35 mg/kg, ip on day 1 | 26652717 | |
| LoVo | Function assay | 30 mins | EC50 = 0.0025 μM | 25761096 | |
| LoVo | Function assay | 30 mins | EC50 = 0.00251 μM | 26652717 | |
| MDA-MB-436 | Antiproliferative assay | 7 days | IC50 = 0.0007 μM | 28692916 | |
| Capan1 | Antiproliferative assay | 7 days | IC50 = 0.0018 μM | 28692916 | |
| VC8 | Cytotoxicity assay | 3 days | IC50 = 0.0042 μM | 28692916 | |
| V79 | Cytotoxicity assay | 3 days | IC50 = 5.0114 μM | 28692916 | |
| NALM-6 | Growth Inhibition Assay | IC50=49 nM | 25263539 | ||
| CHLA-136 | Growth Inhibition Assay | IC50=14.2 nM | 25263539 | ||
| CHLA-90 | Growth Inhibition Assay | IC50> 1,000 nM | 25263539 | ||
| NB-EBc1 | Growth Inhibition Assay | IC50=25.8 nM | 25263539 | ||
| NB-1643 | Growth Inhibition Assay | IC50=18.4 nM | 25263539 | ||
| SJ-GBM2 | Growth Inhibition Assay | IC50=16.2 nM | 25263539 | ||
| CHLA-258 | Growth Inhibition Assay | IC50=4.6 nM | 25263539 | ||
| CHLA-10 | Growth Inhibition Assay | IC50=67.8 nM | 25263539 | ||
| CHLA-9 | Growth Inhibition Assay | IC50=8.2 nM | 25263539 | ||
| TC-71 | Growth Inhibition Assay | IC50=3.7 nM | 25263539 | ||
| CHLA-266 | Growth Inhibition Assay | IC50> 1,000 nM | 25263539 | ||
| BT-12 | Growth Inhibition Assay | IC50> 1,000 nM | 25263539 | ||
| Rh30 | Growth Inhibition Assay | IC50=31.1 nM | 25263539 | ||
| Rh18 | Growth Inhibition Assay | IC50=4.9 nM | 25263539 | ||
| Rh41 | Growth Inhibition Assay | IC50=8.1 nM | 25263539 | ||
| RD | Growth Inhibition Assay | IC50=8.7 nM | 25263539 | ||
| MIA PaCa-2 | Growth Inhibition Assay | IC50=58.23 ± 8.1 µM | 25864590 | ||
| Capan-1 | Growth Inhibition Assay | IC50=16.0 ± 5.4 µM | 25864590 | ||
| COG-LL-317 | Growth Inhibition Assay | IC50=9.4 nM | 25263539 | ||
| RS4;11 | Growth Inhibition Assay | IC50=52.6 nM | 25263539 | ||
| MOLT-4 | Growth Inhibition Assay | IC50=16.6 nM | 25263539 | ||
| CCRF-CEM | Growth Inhibition Assay | IC50=697.3 nM | 25263539 | ||
| Kasumi-1 | Growth Inhibition Assay | IC50=786.2 nM | 25263539 | ||
| Karpas-299 | Growth Inhibition Assay | IC50=75.7 nM | 25263539 | ||
| Ramos-RA1 | Growth Inhibition Assay | IC50=68.3 nM | 25263539 | ||
| DT40 | Growth Inhibition Assay | IC50=4 nM | 24356813 | ||
| DU145 | Growth Inhibition Assay | IC50=11 nM | 24356813 | ||
| H209 | Growth Inhibition Assay | IC50=1.7 nM | 24077350 | ||
| H1048 | Growth Inhibition Assay | IC50=2.2 nM | 24077350 | ||
| H524 | Growth Inhibition Assay | IC50=3.1 nM | 24077350 | ||
| H1930 | Growth Inhibition Assay | IC50=4.1 nM | 24077350 | ||
| H69 | Growth Inhibition Assay | IC50=5.2 nM | 24077350 | ||
| H2081 | Growth Inhibition Assay | IC50=6.3 nM | 24077350 | ||
| H2107 | Growth Inhibition Assay | IC50=7.3 nM | 24077350 | ||
| H1092 | Growth Inhibition Assay | IC50=8.9 nM | 24077350 | ||
| DMS-79 | Growth Inhibition Assay | IC50=9.3 nM | 24077350 | ||
| H446 | Growth Inhibition Assay | IC50=13 nM | 24077350 | ||
| COR-L279 | Growth Inhibition Assay | IC50=15 nM | 24077350 | ||
| MX1 | Cytotoxicity assay | EC50 = 0.0003 μM | 26652717 | ||
| Capan1 | Cytotoxicity assay | EC50 = 0.005 μM | 26652717 | ||
| MRC5 | Cytotoxicity assay | EC50 = 0.31 μM | 26652717 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Talazoparib (BMN 673, LT-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。 | ||
|---|---|---|---|
| 特性 | 到目前为止报道的最有效的选择性PARP抑制剂。 | ||
| 靶点 |
|
| 体外研究(In Vitro) | ||||
| 体外研究活性 | 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]
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|---|---|---|---|---|
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | pKAP1 / pChk2 / pChk1 cleaved-PARP / cleaved-caspase3 / γ-H2AX p-ATM PD-L1 |
|
28947502 | |
| Growth inhibition assay | Cell viability |
|
29158830 | |
| Immunofluorescence | cleaved PARP / 53BP1 RAD51 |
|
28958991 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | 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] |
|
|---|---|---|
| 动物实验 | Animal Models | MX-1模型(BRCA-1缺陷的) |
| Dosages | 0.33 mg/kg/day,每天一次 | |
| Administration | 口服处理 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT05425862 | Suspended | Metastatic Castration Resistant Prostate Cancer (mCRPC) |
Peter MacCallum Cancer Centre Australia |
October 21 2022 | Phase 1 |
| NCT05141708 | Completed | Metastatic Breast Cancer|Breast Neoplasms |
Pfizer |
December 17 2021 | -- |
| NCT05053854 | Recruiting | Neuroendocrine Tumors |
Peter MacCallum Cancer Centre Australia |
December 8 2021 | Phase 1 |
| NCT04991480 | Active not recruiting | Advanced Cancer|Metastatic Cancer|Breast Cancer |
Artios Pharma Ltd |
September 13 2021 | Phase 1|Phase 2 |
| NCT04987931 | Completed | Breast Cancer |
Pfizer |
August 20 2021 | -- |
化学信息&溶解度
| 分子量 | 380.35 | 分子式 |
C19H14F2N6O
|
| CAS号 | 1207456-01-6 | SDF | -- |
| Smiles | CN1C(=NC=N1)C2C(NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 76 mg/mL ( (199.81 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
|
体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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常见问题及建议解决方法
问题 1:
Which solvent do you recommend to dilute the inhibitor for in vivo study in mice?
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"
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