GATA4-NKX2-5-IN-1
(Synonyms: 3i-1000) 目录号 : GC25450GATA4-NKX2-5-IN-1 (3i-1000) is a small-molecule compound inhibiting GATA4 and NKX2-5 transcriptional synergy with IC50 of 3 uM
Cas No.:544681-96-1
Sample solution is provided at 25 µL, 10mM.
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GATA4-NKX2-5-IN-1 (3i-1000) is a small-molecule compound inhibiting GATA4 and NKX2-5 transcriptional synergy with IC50 of 3µM [1].
GATA4-NKX2-5-IN-1 inhibits hypertrophic growth. GATA4-NKX2-5-IN-1 (10µM, 48h) significantly inhibited the increase in the area of the myocytes in response to the mechanical stretching (48h) [1]. GATA4-NKX2-5-IN-1 (30µM), inhibited epidermal growth factor receptor kinase (EGFR) by 54% and vascular endothelial growth factor receptor 2 kinase/kinase insert domain receptor (VEGFR2/KDR) by 64% [1]. GATA4-NKX2-5-IN-1 inhibited cannabinoid receptor type 2 (CB2), parathyroid hormone 2 receptor (PTH2), and niacin receptor 1/G-protein-coupled receptor 109A (GPR109A) with mean percentage inhibition values of 91.8, 59.5, and 58.5, respectively [1]. GATA4-NKX2-5-IN-1 inhibits BNP transcription, and stretch-, endothelin-1- and phenylephrine-stimulated gene expression of ANP and BNP, as well as hypertrophic cell growth in cardiomyocytes while having no effect on GATA4 or NKX2-5 DNA binding or on the activity of protein kinases involved in the regulation of GATA4 phosphorylation [1,2]. GATA4-NKX2-5-IN-1 showed cardioprotective effects in vitro. It attenuated doxorubicin-induced increase in proBNP expression in hiPSC-CMs after a 4-day exposure. GATA4-NKX2-5-IN-1 (3 µM, 10 µM) attenuated doxorubicin-induced increase in caspase activation up to 14 days. however the long-term exposures (up to 21 days), revealed toxic effects of GATA4-NKX2-5-IN-1 in cardiomyocytes [3].
GATA4-NKX2-5-IN-1(30mg/kg/day i.p.) significantly improved left ventricular ejection fraction and fractional shortening, and attenuated myocardial structural changes in mice after myocardial infarction. GATA4-NKX2-5-IN-1 improved cardiac function in an experimental model of angiotensin II -mediated hypertension in rats. The concentration of GATA4-NKX2-5-IN-1 was highest at 0.5h and decreased to about half within 6h in vivo in rats (single dose i.p. 10mg/kg) [2].
References:
[1]. Va?lima?ki M J, To?lli M A, Kinnunen S M, et al. Discovery of small molecules targeting the synergy of cardiac transcription factors GATA4 and NKX2-5[J]. Journal of Medicinal Chemistry, 2017, 60(18): 7781-7798.
[2]. Kinnunen S M, TÖlli M, VÄlimÄki M J, et al. Cardiac actions of a small molecule inhibitor targeting GATA4-NKX2-5 interaction[J]. Scientific reports, 2018, 8(1): 1-14.
[3]. Karhu S T, Kinnunen S M, TÖlli M, et al. GATA4-targeted compound exhibits cardioprotective actions against doxorubicin-induced toxicity in vitro and in vivo: establishment of a chronic cardiotoxicity model using human iPSC-derived cardiomyocytes[J]. Archives of Toxicology, 2020, 94(6): 2113-2130.
| Cell experiment [1]: | |
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Cell lines |
human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) cells |
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Preparation Method |
The cells were exposed to doxorubicin and/or GATA4-NKX2-5-IN-1 for 2-21 days and cell viability was quantified with MTT assay. MTT was added to the cells at a final concentration of 0.5 mg/ml followed by 2 h incubation in cell culture conditions. |
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Reaction Conditions |
0-10 µM, 2-21 days |
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Applications |
In the MTT assay, GATA4-NKX2-5-IN-1 alone at 10 µM concentration reduced hiPSC-CM viability 34%, 50% and 65% after 7, 14 and 21 days of exposure, respectively. At the concentration of 3 µM, the decrease was only 16% even after 21-day exposure. |
| Animal experiment [2]: | |
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Animal models |
male Sprague Dawley rats |
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Preparation Method |
Doxorubicin was administered i.p. to 7 weeks old male Sprague Dawley rats with average weight 216 g (range 189-245 g) at the dose of 1 mg/kg/day for 10 days. Control animals received an equivalent volume of saline. The compound GATA4-NKX2-5-IN-1 was administered i.p. at the dose of 15 mg/kg two times a day for 2 weeks from week 7 to week 9. It was diluted to DMSO and administered to animals as 1:1 dilution in corn oil, control animals receiving DMSO with corn oil in equivalent volume. |
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Dosage form |
15 mg/kg two times a day for 2 weeks, i.p. |
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Applications |
treatment with compound GATA4-NKX2-5-IN-1 significantly inhibited doxorubicin-induced cardiotoxicity by restoring the left ventricular ejection fraction (EF) and fractional shortening (FS). |
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References: [1]: Karhu S T, Kinnunen S M, TÖlli M, et al. GATA4-targeted compound exhibits cardioprotective actions against doxorubicin-induced toxicity in vitro and in vivo: establishment of a chronic cardiotoxicity model using human iPSC-derived cardiomyocytes[J]. Archives of Toxicology, 2020, 94(6): 2113-2130. | |
| Cas No. | 544681-96-1 | SDF | Download SDF |
| 别名 | 3i-1000 | ||
| 分子式 | C21H23N3O2 | 分子量 | 349.43 |
| 溶解度 | DMSO: 70 mg/mL (200.33 mM);Water: Insoluble;Ethanol: 9 mg/mL (25.76 mM) | 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 | 2.8618 mL | 14.309 mL | 28.618 mL |
| 5 mM | 0.5724 mL | 2.8618 mL | 5.7236 mL |
| 10 mM | 0.2862 mL | 1.4309 mL | 2.8618 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。
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet