Talazoparib (BMN 673)

製品コードS7048 バッチS704805

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	76 mg/mL warmed with 50ºC water bath (199.81 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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] 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
Transcription-replication conflicts underlie sensitivity to PARP inhibitors [ Nature, 2024, 628(8007):433-441]	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
GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer [ Nat Commun, 2024, 15(1):2132]	PubMed: 38459011
Discovery of a small-molecule inhibitor that traps Polθ on DNA and synergizes with PARP inhibitors [ Nat Commun, 2024, 15(1):2862]	PubMed: 38580648
PARP1-dependent DNA-protein crosslink repair [ Nat Commun, 2024, 15(1):6641]	PubMed: 39103378
H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours [ Nat Commun, 2024, 15(1):4430]	PubMed: 38789420
BRCA1 levels and DNA-damage response are controlled by the competitive binding of circHIPK3 or FMRP to the BRCA1 mRNA [ Mol Cell, 2024, S1097-2765(24)00773-1]	PubMed: 39389065
The MYCN oncoprotein is an RNA-binding accessory factor of the nuclear exosome targeting complex [ Mol Cell, 2024, S1097-2765(24)00285-5]	PubMed: 38703770
DNA-PK participates in pre-rRNA biogenesis independent of DNA double-strand break repair [ Nucleic Acids Res, 2024, gkae316]	PubMed: 38682589

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。

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