AZ6102

製品コードS7767 バッチS776701

印刷

化学情報

Chemical Structure Synonyms AZ-6102 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H28N6O
分子量 428.53 CAS No. 1645286-75-4
Solubility (25°C)* 体外 DMSO 85 mg/mL (198.35 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 AZ6102 is a potent TNKS1/2 inhibitor that has 100-fold selectivity against other PARP family enzymes and shows IC50 of 5 nM for Wnt pathway inhibition in DLD-1 cells.
in vitro AZ6102 inhibits TNKS1 and TNKS2 in enzymatic assays and TCF4 reporter assays (<5nM). AZ6102 inhibits proliferation of Colo320DM (GI50 ~40nM), but has no anti-proliferative activity in the β-catenin mutant cell line HCT-116, or the BRCA mutant cell line MDA-MB-436. In Colo320DM, AZ6102 stabilizes axin2 protein and modulates Wnt target genes in a dose and time dependent manner both in vitro and in vivo[1].
in vivo Nude mice are administered 25 mg/kg of AZ-6102. The compound has a half-life of 4 hours and a CL of 24 mL/min.kg. Further analysis in mouse and rats shows that AZ-6102 has a moderate bioavailability at 12% and 18%, respectively. Western blot analysis for TNKS1, TNSK2 and Axin2 of treated DLD-1 cells shows that AZ-6102 had qualitatively stronger and longer lasting stabilization of TNSK1, TNSK2 and Axin2 than XAV-939 at lower concentrations (at 24, 48 and 72h). AZ-6102 has good pharmacokinetics in preclinical species with low Caco2 efflux (to avoid possible tumor resistance mechanisms). In addition, the compound can be formulated in a clinically relevant intravenous solution at 20 mg/mL using SBECD as an excipient at pH4. The results of AZ-6102 used as an i.v. probe compound to explore the in vivo effects of the inhibition of TNKS1 and TNSK2 on tumor xenografts and normal tissue are forthcoming[2].

プロトコル(参考用のみ)

キナーゼアッセイ TNKS1 enzyme Scintillation Proximity Assay (SPA)
The assay is designed to measure compound inhibition of Tankyrase-1 autoPARsylation (Tankyrase-1 was both enzyme and substrate in this assay). Truncated recombinant human Tankyrase-1 protein (amino acids E1023-T1327; molecular weight,37,111 Dalton)is purified from SF9 cells. The assay is conducted using 0.11 µM of Tankyrase-1 protein and 3 µM Nicotinamide Adenine Dinucleotide (NAD+, 2.12µM 3H-NAD+ with a specific radioactivity of 1690 Ci/mol, 0.88 µM biotin- NAD+), in pH 7.5 Tris buffer (60 mM Tris, 1 mM DTT, 0.01% (v/v) Tween-20®, 2.5 mMMgCl2, 0.3 mg/mL BSA). For IC50 determination, 10mM DMSO stock solution of a compound is sequentially diluted by two-fold in DMSO, and aliquots of the diluted solutions are transferred to 384-well assay plates and mixed with Tankyrase-1 solution. Normally, ten compound concentrations are included varying from 8.3µM to 0.3nM. Reactions are initiated by adding the NAD+ mixture, and run at room temperature for 90 minutes. Subsequently the reactions are quenched by adding a detection mixture made of 100µg/well scintillant coated Streptavidin beads (PerkinElmer) in pH7.4 Tris buffer (60mM Tris,50mM NaCl), incubated at 25°C for overnight, and read with a radioactivity counter.

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：

USP25 promotes pathological HIF-1-driven metabolic reprogramming and is a potential therapeutic target in pancreatic cancer [ Nat Commun, 2022, 13(1):2070] PubMed: 35440539
Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death [ Sci Adv, 2022, 8(19):eabh2332] PubMed: 35544574
Characterization of GECPAR, a noncoding RNA that regulates the transcriptional program of diffuse large B cell lymphoma [ Haematologica, 2021, 10.3324/haematol.2020.267096] PubMed: 34162177
Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation. [ Nat Commun, 2019, 10(1):4898] PubMed: 31653858
Identification of Novel Target for Osteosarcoma by Network Analysis [ Med Sci Monit, 2018, 24:5914-5924] PubMed: 30144309

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。