Talazoparib (BMN 673)

製品コードS7048 バッチS704810

印刷

化学情報

Synonyms

LT-673

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₉H₁₄F₂N₆O

分子量

380.35

CAS No.

1207456-01-6

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

76 mg/mL (199.81 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution	5%DMSO 1 95% Corn oil	0.625mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/mL clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O	2.5mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/mL clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify; add 50 μL Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	タラゾパリブ (Talazoparib (BMN 673、LT-673)) は、新規 PARP 阻害剤 (無細胞アッセイで IC50 = 0.57 nM) です。また PARP-2 の強力な阻害剤でもありますが、PARG を阻害せず PTEN 変異に非常に敏感です。臨床フェーズ 3。
in vitro	BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. BMN 673 selectively kills cancer cells with BRCA-1 or BRCA-2 mutations. BMN 673 demonstrates single-agent cytotoxicityin BRCA-1 mutant (MX-1, IC50 = 0.3 nM) and BRCA-2 mutant cells (Capan-1, IC50 = 5 nM). In contrast, in MRC-5 normal human fibroblastand other tumor cell lines with wild-type BRCA-1 and BRCA-2 genes, IC50 of BMN 673 ranges between 90 nM and 1.9 μM. ^[1] In cultured human cancer cells, BMN 673 also significantly enhances the cytotoxic efficacy of both Temozolomide and SN-38. Off-target molecular screening did not identify significant non-specific activity for this class of PARP inhibitors. ^[2]
in vivo	In rat pharmacokinetic studies, BMN 673 displays >50% oralbioavailability and pharmacokinetic properties that enable singledaily dosing. In MX-1 xenograft tumor model studies, daily oral dosingof BMN 673 significantly enhances the antitumor effects ofcytotoxic therapies in a dose-dependent manner. ^[2]
特徴	Most potent and selective PARPi reported thus far.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MDA-MB-436 cells
	濃度	10 uM
	反応時間	7 days
	実験の流れ	Cells were treated with increasing doses of talazoparib for 7 days and subjected to cell viability assays to derive IC50 values.
動物実験	動物モデル	MX-1 model (BRCA-1 deficient)
	投薬量	0.33 mg/kg/day, once daily
	投与方法	Oral

参考

カスタマーフィードバック

: , , Clin Cancer Res, 2017, 23(13):3405-3415

: Data from [Data independently produced by , , Nature, 2018, 559(7713):285-289]

: Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(14):3711-3720]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Transcription-replication conflicts underlie sensitivity to PARP inhibitors [ Nature, 2024, 10.1038/s41586-024-07217-2]	PubMed: 38509368
Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3]	PubMed: 38262581
A CANCER PERSISTENT DNA REPAIR CIRCUIT DRIVEN BY MDM2, MDM4 (MDMX), AND MUTANT P53 FOR RECRUITMENT OF MDC1 AND 53BP1 TO [ bioRxiv, 2024, 2024.01.20.576487.]	PubMed: 38328189
SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response [ Nat Genet, 2023, 55(8):1311-1323]	PubMed: 37524790
Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA [ Nucleic Acids Res, 2023, gkad150]	PubMed: 36940725
Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA [ Nucleic Acids Research, 2023, 51(13)-]	PubMed: None
Real-time imaging of drug-induced trapping of cellular topoisomerases and poly-ADP-ribose) polymerase 1 at the single-molecule level [ Nucleic Acids Res, 2023, 51(18):e97]	PubMed: 37670571
PRMT blockade induces defective DNA replication stress response and synergizes with PARP inhibition [ Cell Rep Med, 2023, 4(12):101326]	PubMed: 38118413
Widespread BRCA1/2-independent homologous recombination defects are caused by alterations in RNA-binding proteins [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101255]	PubMed: 37909041
Bispecific antibodies targeting EGFR/Notch enhance the response to talazoparib by decreasing tumour-initiating cell frequency [ Theranostics, 2023, 13(11):3641-3654]	PubMed: 37441599

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。