Veliparib (ABT-888)

製品コードS1004 バッチS100418

印刷

化学情報

Synonyms

NSC 737664

Storage
(From the date of receipt)

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

化学式

C₁₃H₁₆N₄O

分子量

244.29

CAS No.

912444-00-9

Solubility (25°C)*

体外

DMSO

48 mg/mL (196.48 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）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (20.47mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of 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	Veliparib (ABT-888, NSC 737664)は、細胞を含まないアッセイで、PARP1およびPARP2の強力な阻害剤であり、K_i値はそれぞれ5.2 nMおよび2.9 nMです。SIRT2には不活性です。Veliparibはautophagyとapoptosisを増加させます。フェーズ3。
in vitro	Veliparib (ABT-888) is inactive to SIRT2 (>5 μM). It inhibits the PARP activity with EC50 of 2 nM in C41 cells. This compound could decrease the PAR levels in both irradiated and nonirradiated H460 cells. It also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. When combined with radiation, it increases apoptosis and autophagy in H460 cells. It also inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. At 10 μM, it suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. It shows effective radiosensitivity in oxic H1299 cells. Furthermore, it could attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1.
in vivo	Veliparib (ABT-888) has an oral bioavailability of 56%-92% in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys after oral administration. This compound (25 mg/kg i.p.) could improve tumor growth delay in a NCI-H460 xenograft model with well tolerated. Combination with radiation, it decreases the tumor vessel formation. It reduces intratumor PAR levels by more than 95% at a dose of 3 and 12.5 mg/kg in A375 and Colo829 xenograft models and the suppression could be maintained over time.
特徴	Increases the efficacy of common cancer therapies such as radiation and alkylating agents.

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro PARP assays
キナーゼアッセイ	PARP assays for Veliparib (ABT-888) are conducted in a buffer containing 50 mM Tris (pH 8.0), 1 mM DTT, 1.5 μM [³H]NAD⁺ (1.6 μCi/mmol), 200 nM biotinylated histone H1, 200 nM slDNA, and 1 nM PARP-1 or 4 nM PARP-2 enzyme. Reactions are terminated with 1.5 mM benzamide, transferred to streptavidin Flash plates, and counted using a TopCount microplate scintillation counter.
細胞アッセイ	細胞株	Cell-free assays
	濃度	Ki of 5.2 and 2.9 nM for PARP1 and PARP2
	反応時間
	実験の流れ
動物実験	動物モデル	NCI-H460, H460, B16F10 and 9L xenografts in C57BL/6 mice
	投薬量	~25 mg/kg
	投与方法	Orally administered

参考

https://pubmed.ncbi.nlm.nih.gov/17473206/
https://pubmed.ncbi.nlm.nih.gov/19143569/
https://pubmed.ncbi.nlm.nih.gov/17505006/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766769/
https://pubmed.ncbi.nlm.nih.gov/19934293/
https://pubmed.ncbi.nlm.nih.gov/17473206/
https://pubmed.ncbi.nlm.nih.gov/22678161/

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カスタマーフィードバック

: Data from [Nucl Med Commun, 2011, 32, 1046-1051]

: Data from [Nucl Med Commun, 2011, 32(11), 1046-51]

: Data from [Nucl Med Commun, 2011, 32(11), 1046-51]

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：

EXO1 as a therapeutic target for Fanconi Anaemia, ZRSR2 and BRCA1-A complex deficient cancers [ Nat Commun, 2025, 16(1):8476]	PubMed: 41006228
CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair [ Nat Commun, 2025, 16(1):1026]	PubMed: 39863586
PARP7 inhibits type I interferon signaling to prevent autoimmunity and lung disease [ J Exp Med, 2025, 222(5)e20241184]	PubMed: 39969510
Combining Multiplexed CRISPR/Cas9-Nickase and PARP Inhibitors Efficiently and Precisely Targets Cancer Cells [ Cancer Res, 2025, 10.1158/0008-5472.CAN-24-2938]	PubMed: 40327605
ZNF251 haploinsufficiency confers PARP inhibitors resistance in BRCA1-mutated cancer cells through activation of homologous recombination [ Cancer Lett, 2025, 613:217505]	PubMed: 39892701
Role of KLF5 in enhancing ovarian cancer stemness and PARPi resistance: mechanisms and therapeutic targeting [ J Transl Med, 2025, 23(1):492]	PubMed: 40307891
Poly ADP Ribose Polymerase Inhibitors Potentiate Proton Therapy End-of-Range Effects by Accelerating Replication Forks and Promoting Transcription Conflict [ Int J Radiat Oncol Biol Phys, 2025, S0360-3016(25)06197-8]	PubMed: 40882877
PARP inhibitors elicit distinct transcriptional programs in homologous recombination competent castration-resistant prostate cancer [ Mol Oncol, 2025, 10.1002/1878-0261.70098]	PubMed: 40915979
Homologous Repair-Deficient Pancreatic Cancer: Refined Targeting of DNA Damage Response is an Effective Therapeutic Strategy [ United Eur Gastroent, 2025, 13(7):1328-1342]	PubMed: 40823818
Tousled-like kinase loss confers PARP inhibitor resistance in BRCA1-mutated cancers by impeding non-homologous end joining repair [ Mol Med, 2025, 31(1):18]	PubMed: 39844055

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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