CDK7-IN-20

CDK7 4 nM (IC50) CDK1 3375 nM (IC50) CDK2 823 nM (IC50) CDK3 1837 nM (IC50) CDK5 >10,000 nM (IC50) CDK6 950 nM (IC50) CDK9 526 nM (IC50) CDK12 >10,000 nM (IC50) GSK3β 148 nM (IC50)

化合物 B2（CDK7-IN-20）在 Madin-Darby 犬肾 (MDCK) 细胞中与 THZ1 相比，在抑制囊肿形成和降低细胞毒性方面表现出巨大的有效性，从第 4 天到第 12 天的浓度范围为 1-3 μM[1] 。

化合物 B2 (CDK7-IN-20) 每天一次皮下注射 5 mg/kg，持续 6 天，可显着减小 ADPKD 小鼠肾脏的大小并防止囊肿形成。在 ADPKD 小鼠肾脏的囊肿衬里上皮细胞中，CDK7-IN-20 可能会显着降低 AMPD3 蛋白表达[1]。化合物 B2)a（CDK7-IN-20 的 ADME 谱）[1]。化合物 B2 的特征，CDK7-IN-20 sc 5 mg/kg，iv 5 mg/kg AUClast (h^ng/mL) 26,937 17,280 t1/2 (h) AUCIFN_obs (h·ng/mL) 31,698 17,411 17.8 3.4 Tmax（小时） 0.5 Cmax（小时） Cl_obs (mL/min/kg) = 3806 Vss_obs (mL/kg) = 2.80 MRTIFN_obs (h) = 1275 10.2 4.8 F (%) 64.2 结合血浆蛋白 A 至 B 的百分比 Papp (10 –6 cm/s)/B 至 A Papp (10–6 cm/s)/Caco-2 的渗透性 b >99/流出率 c <0.133/6.370/>48.0 a 每组给予三只 ICR 小鼠。给出了数据的平均值。老鼠的血浆。 PPB 使用 1 和 10 μM 的底物剂量进行了测试。 bCaco-2 底物浓度为 10 μM 时的膜渗透性。使用定量限 (1.0 nM) 确定 0.133[1] 的值。

Animal/Disease Models: Neonatal Pkd1flox/flox:Ksp-Cre mice[1]
Doses: 5 mg /kg
Route of Administration: subcutaneous (sc) administration; one time/day; for 6 days
Experimental Results: Dramatically decreased the kidney size and cyst formation of the ADPKD mice.

[1]. Bowen Yang, et al. Discovery of Novel N-(5-(Pyridin-3-yl)-1 H-indazol-3-yl)benzamide Derivatives as Potent Cyclin-Dependent Kinase 7 Inhibitors for the Treatment of Autosomal Dominant Polycystic Kidney Disease. J Med Chem. 2022 Nov 17.

C30H26N6O3

518.57

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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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。