AZ6102
(Synonyms: REL-2-[4-[6-[(3R,5S)-3,5-二甲基-1-哌嗪基]-4-甲基-3-吡啶基]苯基]-3,7-二氢-7-甲基-4H-吡咯并[2,3-D]嘧啶-4-酮) 目录号 : GC16725
A TNKS1/2 inhibitor
Cas No.:1645286-75-4
Sample solution is provided at 25 µL, 10mM.
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IC50: 1 and 3 nM for TNKS2 and TNKS1, respectively
AZ6102 is a TNKS1/2 inhibitor.
Inhibition of the poly(ADP-ribose) polymerase (PARP) catalytic domain of the tankyrases (TNKS1 and TNKS2) is reported to inhibit the Wnt pathway by increasing stabilization of Axin. The canonical Wnt pathway plays a critical role in adult tissue homeostasis, embryonic development, as well as cancer.
In vitro: AZ6102 was identified as a potent TNKS1/2 inhibitor with 100-fold selectivity against other PARP family enzymes including PARPs 1, 2, and 6. In addition, AZ6102 showed a 5 nM IC50 against Wnt pathway in DLD-1 cells [1].
In vivo: In animal study, AZ6102 was intravenously dosed to nude mice at 25 mg/kg, and the results showed that AZ6102 had a clearance of 24 mL/min·kg and a half-life of 4 h. The bioavailability of AZ6102 in mouse and rat was only moderate at 12% and 18%, respectively. In addition, AZ6102 was used as an intravenous probe compound to evaluate the in vivo effects of TNKS1/2 inhibition on normal tissue and tumor xenografts, however, the results of such experiments have not be released so far [1].
Clinical trial: Up to now, AZ6102 is still in the preclinical development stage.
Reference:
[1] J. W. Johannes, L. Almeida, B. Barlaam,et al.Pyrimidinone nicotinamide mimetics as selective tankyrase and Wnt pathways inhibitors suitable for in vivopharmacology. ACS Med. Chem. Lett. 6, 254-259 (2015).
Kinase experiment: | The assay is conducted using 0.11 μM of tankyrase-1 protein and 3 μM nicotinamide adenine dinucleotide (NAD+, 2.12 μM 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 mM MgCl2, 0.3 mg/mL BSA). For IC50 determination, 10 mM DMSO stock solution of a compound (AZ6102) 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[1]. |
References: [1]. Johannes JW, et al. Pyrimidinone nicotinamide mimetics as selective tankyrase and wnt pathway inhibitors suitable for in vivo pharmacology. ACS Med Chem Lett. 2015 Jan 13;6(3):254-9. | |
| Cas No. | 1645286-75-4 | SDF | |
| 别名 | REL-2-[4-[6-[(3R,5S)-3,5-二甲基-1-哌嗪基]-4-甲基-3-吡啶基]苯基]-3,7-二氢-7-甲基-4H-吡咯并[2,3-D]嘧啶-4-酮 | ||
| 化学名 | 2-(4-(6-((3S,5R)-3,5-dimethylpiperazin-1-yl)-4-methylpyridin-3-yl)phenyl)-7-methyl-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one | ||
| Canonical SMILES | O=C1NC(C2=CC=C(C3=CN=C(N4C[C@H](C)N[C@H](C)C4)C=C3C)C=C2)=NC5=C1C=CN5C | ||
| 分子式 | C25H28N6O | 分子量 | 428.53 |
| 溶解度 | DMF: 15 mg/ml,DMF:PBS(pH7.2) (1:2): 0.3 mg/ml,DMSO: 10 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3336 mL | 11.6678 mL | 23.3356 mL |
| 5 mM | 0.4667 mL | 2.3336 mL | 4.6671 mL |
| 10 mM | 0.2334 mL | 1.1668 mL | 2.3336 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet