Bay 65-1942 是一种 ATP 竞争性抑制剂，可选择性地靶向 IKKbeta 激酶活性，在缺血前、再灌注时或再灌注后 2 小时腹膜内注射。与未接受治疗的动物相比，接受 IKKbeta 抑制剂治疗的小鼠左心室梗塞面积显著减少。在预先接受 IKKbeta 抑制剂治疗后，心脏功能也得到了保留。[1]

IKKβ inhibition decreases size of infarction.
Delivery of Bay 65-1942 prior to ischemia significantly decreased left ventricular infarct size compared with animals receiving vehicle . Compared with sham animals, animals receiving vehicle had a significant increase in the infarct-to-AAR ratio . This ratio was significantly reduced by treatment with Bay 65-1942 at each time point (prior to ischemia 42.7 ± 4.1%, at reperfusion 42.7 ± 7.5%, 2 h of reperfusion 29.4 ± 5.2%; each group P < 0.05 vs. vehicle). The differences in this ratio between those pretreated with the IKKβ inhibitor and those that received the inhibitor in a delayed fashion were not significant. No significant differences in AAR existed between sham, vehicle, and treatment groups .[1]

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IKKβ inhibition attenuates myocardial injury.
Myocardial injury was assessed with the measurement of serum CK-MB levels 1 h following reperfusion. The CK-MB fraction was significantly elevated in the vehicle group (n = 3) compared with the sham group (n = 4) (30,530 ± 371.2 vs. 9,675 ± 608.4 units, P < 0.05). Animals pretreated with Bay 65-1942 (n = 3) had significantly attenuated CK-MB levels compared with those animals without treatment prior to IR (14,170 ± 3,219 units, P < 0.05 vs. vehicle).[1]

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IKKβ inhibition preserves cardiac function.
We assessed cardiac function by comparing pressure-volume recordings in mice at baseline and following IR with or without Bay 65-1942. Bay 65-1942 administration alone did not improve myocardial function above baseline hemodynamic parameters. Ejection fraction (EF) and dP/dt (the first derivative of left ventricular pressure) were significantly lower in the mice that underwent 30 min of LAD occlusion followed by 3 days of reperfusion when compared with the baseline group and the group administered Bay 65-1942 without surgery. The treatment group had a significantly improved EF and dP/dt from the IR with vehicle group, whereas no difference existed when compared with the baseline groups.[1]

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IKKβ inhibition decreases NF-κB-associated protein expression.
Western blots on left ventricular homogenates from sham, vehicle, and pretreatment groups (n = 3 for each group) killed 30 min and 1 h after reperfusion were performed to observe the effects of IKKβ inhibition on the NF-κB pathway . Expression of phospho-IκBα, the direct downstream product of IKKβ activation, was significantly elevated in vehicle animals compared with sham animals 30 min after reperfusion (P < 0.05). This difference between sham and vehicle groups was statistically lost 1 h following reperfusion, suggesting that initial IKKβ activation is at its height within 1 h of reperfusion injury. Animals treated with Bay 65-1942 had lower levels of phospho-IκBα expression compared with the vehicle group at both 30 min and 1 h following reperfusion (P < 0.05, Bay 65-1942 vs. vehicle).[1]

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IKKβ inhibition decreases TNF-α and IL-6 expression.
TNF-α and IL-6 are NF-κB-dependent cytokines activated in response to myocardial injury. One hour after reperfusion, levels of TNF-α and IL-6 were significantly elevated in the vehicle groups compared with the sham animals (TNF-α: 248.6 ± 25 vs. 35.1 ± 35.1 pg/ml, P < 0.05; IL-6: 5,974 ± 1,976 vs. 433.9 ± 83.1 pg/ml, P < 0.05). When administered Bay 65-1942 prior to ischemia, the amount of serum TNF-α dropped significantly compared with the vehicle group (22.4 ± 7.3 pg/ml, P < 0.05 vs. vehicle). IL-6 was also significantly lower in animals that received the IKKβ inhibitor compared with vehicle animals (417.8 ± 118.2 pg/ml, P < 0.05 vs. vehicle). There were no differences in cytokine concentrations between sham and treatment animals.[1]

Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2248-53.;PLoS One. 2013 Jun 24;8(6):e66755.

C22H25N3O4

395.4516

395.185

758683-21-5

600734-02-9; 600734-06-3 (HCl salt)

136091530

White to gray solid

3.55

96.2

3

6

5

29

586

1

OC1=CC=CC(OCC2CC2)=C1C3=NC(NC(OC4)=O)=C4C([C@H]5CCCNC5)=C3

IGJVFGZEWDGDOO-AWEZNQCLSA-N

InChI=1S/C22H25N3O4/c26-18-4-1-5-19(28-11-13-6-7-13)20(18)17-9-15(14-3-2-8-23-10-14)16-12-29-22(27)25-21(16)24-17/h1,4-5,9,13-14,23,26H,2-3,6-8,10-12H2,(H,24,25,27)/t14-/m0/s1

7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3R)-piperidin-3-yl]-1,4-dihydropyrido[2,3-d][1,3]oxazin-2-one

BAY 65-1942 R-isomer; BAY-65-1942; BAY65-1942; BAY 651942; BAY-651942; BAY651942

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。