Aurora Kinase Inhibitor III   中文名称: Aurora激酶抑制剂III

Aurora A (IC50 = 42 nM)

该化合物是2,4-二苯胺基嘧啶类似物。文献提供了类似物的构效关系（SAR）数据：化合物1 (X=C, Y=N, Z=N) 抑制 Aurora A 的 IC50 为 42 nM。其区域异构体化合物2 (X=N, Y=C, Z=N) 效力降低 (IC50 931 nM)。4,6-二取代嘧啶化合物3 (X=N, Y=N, Z=C) 对 Aurora A 的抑制活性非常弱 (IC50 >10,000 nM)。[1]

[1]. Structural basis for the inhibition of Aurora A kinase by a novel class of high affinitydisubstituted pyrimidine inhibitors. Bioorg Med Chem Lett. 2007 Feb 1;17(3):688-91.

The 2.25 Å resolution crystal structure of Aurora A kinase in complex with Aurora Kinase Inhibitor III was determined. The inhibitor binds in the ATP-binding pocket in an s-cis conformation.[1]
The binding mode is novel. The dipyrimidine and aniline moieties mimic adenine, forming two hydrogen bonds with the backbone of A213 in the hinge region. The cyclopropylamide moiety is oriented towards the solvent-exposed region, engaging the carbonyl of P214 and the side chain of R137 via hydrogen bonds. The trifluoromethyl group interacts with the main chain of G142 and the side chain of K143 in the p-loop.[1]
Binding induces conformational changes in the p-loop and the DFG motif compared to other Aurora A structures. The p-loop shifts, and K143 moves to interact with the inhibitor's trifluoromethyl group. The DFG motif adopts a conformation distinct from both the active (DFG-in) and inactive (DFG-out) states observed in other structures, but more closely resembles the activated form.[1]
The solvent-exposed positioning of the cyclopropylamide, in contrast to inhibitors like VX-680 where similar groups bind deeply near the DFG motif, may explain the compound's lack of high kinase selectivity. The analysis suggests that selectivity for Aurora A might be improved by extending the molecule at the trifluoromethyl site to interact more deeply with the DFG region.[1]
The structural analysis explains the SAR: the loss of potency in Compound 2 is likely due to the loss of a hydrogen bond to A213. The dramatic loss in Compound 3 is likely due to the greater energetic penalty required to adopt the necessary s-cis conformation for hinge binding.[1]

C21H18F3N5O

413.4

413.146

C, 61.01; H, 4.39; F, 13.79; N, 16.94; O, 3.87

879127-16-9

9549303

White to off-white solid powder

5.475

85.66

3

8

6

30

586

0

O=C(C1CC1)NC1C=C(NC2N=C(NC3C=C(C(F)(F)F)C=CC=3)C=CN=2)C=CC=1

RDTDWGQDFJPTPD-UHFFFAOYSA-N

InChI=1S/C21H18F3N5O/c22-21(23,24)14-3-1-4-15(11-14)26-18-9-10-25-20(29-18)28-17-6-2-5-16(12-17)27-19(30)13-7-8-13/h1-6,9-13H,7-8H2,(H,27,30)(H2,25,26,28,29)

N-[3-[[4-[3-(trifluoromethyl)anilino]pyrimidin-2-yl]amino]phenyl]cyclopropanecarboxamide

Aurora Kinase Inhibitor III; AKI-7169; AKI7169; AKI 7169

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.08 mg/mL (5.03 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (5.03 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (5.03 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。