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AZ6102
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
AZ6102图片
包装与价格:
包装价格(元)
5mg电议
25mg电议

产品介绍
AZ6102 是一种有效的 TNKS1 和 TNKS2 双重抑制剂,IC50 分别为 3 nM 和 1 nM,alao 对其他 PARP 家族酶的选择性是其他 PARP 家族酶的 100 倍,对 PARP1 的 IC50 分别为 2.0 μM、0.5 μM 和 >3 μM 、PARP2 和 PARP6 分别。

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(R), 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].

产品描述

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).