IMM-H007
目录号 : GC25521IMM-H007, an adenosine derivative, is an activator of AMP-Activated Protein Kinase (AMPK). IMM-H007 is a potential drug for treating cardiac dysfunction. IMM-H007 negatively regulates endothelium inflammation through inactivating NF-κB and JNK/AP1 signaling. IMM-H007 inhibits ABCA1 (ATP binding cassette subfamily a member 1) degradation and facilitates its cell-surface localization in macrophages, thereby promotes cholesterol efflux.
Cas No.:1221412-23-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
IMM-H007, an adenosine derivative, is an activator of AMP-Activated Protein Kinase (AMPK). IMM-H007 is a potential drug for treating cardiac dysfunction. IMM-H007 negatively regulates endothelium inflammation through inactivating NF-κB and JNK/AP1 signaling. IMM-H007 inhibits ABCA1 (ATP binding cassette subfamily a member 1) degradation and facilitates its cell-surface localization in macrophages, thereby promotes cholesterol efflux.
IMM-H007 reduces isoprenaline-induced Smad2/3 phosphorylation downstream of TGFβ1 and cardiac fibrosis via an AMPKα2-independent pathway, but the inhibition of TGFβ1 expression is AMPKα2-dependent.[4]
[1] Weipeng Ge, et al. Eur J Pharmacol. 2019 Aug 15;857:172442. [2] Jinjin Yu, et al. Toxicol Appl Pharmacol. 2019 Oct 15;381:114732. [3] LinZhang Huang, et al. J Lipid Res. 2015 May;56(5):986-97.
| Cas No. | 1221412-23-2 | SDF | Download SDF |
| 分子式 | C22H23N5O8 | 分子量 | 485.45 |
| 溶解度 | DMSO: 97 mg/mL (199.81 mM);Water: Insoluble;Ethanol: Insoluble | 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 | 2.0599 mL | 10.2997 mL | 20.5994 mL |
| 5 mM | 0.412 mL | 2.0599 mL | 4.1199 mL |
| 10 mM | 0.206 mL | 1.03 mL | 2.0599 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 | ||||||||||
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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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
IMM-H007 attenuates isoprenaline-induced cardiac fibrosis through targeting TGFβ1 signaling pathway
Acta Pharmacol Sin 2022 Oct;43(10):2542-2549.PMID:PMC9525664DOI:10.1038/s41401-022-00899-2.
Upon chronic stress, β-adrenergic receptor activation induces cardiac fibrosis and leads to heart failure. The small molecule compound IMM-H007 has demonstrated protective effects in cardiovascular diseases via activation of AMP-activated protein kinase (AMPK). This study aimed to investigate IMM-H007 effects on cardiac fibrosis induced by β-adrenergic receptor activation. Because adenosine analogs also exert AMPK-independent effects, we assessed AMPK-dependent and -independent IMM-H007 effects in murine models of cardiac fibrosis. Continual subcutaneous injection of isoprenaline for 7 days caused cardiac fibrosis and cardiac dysfunction in mice in vivo. IMM-H007 attenuated isoprenaline-induced cardiac fibrosis, diastolic dysfunction, α-smooth muscle actin expression, and collagen I deposition in both wild-type and AMPKα2-/- mice. Moreover, IMM-H007 inhibited transforming growth factor β1 (TGFβ1) expression in wild-type, but not AMPKα2-/- mice. By contrast, IMM-H007 inhibited Smad2/3 signaling downstream of TGFβ1 in both wild-type and AMPKα2-/- mice. Surface plasmon resonance and molecular docking experiments showed that IMM-H007 directly interacts with TGFβ1, inhibits its binding to TGFβ type II receptors, and downregulates the Smad2/3 signaling pathway downstream of TGFβ1. These findings suggest that IMM-H007 inhibits isoprenaline-induced cardiac fibrosis via both AMPKα2-dependent and -independent mechanisms. IMM-H007 may be useful as a novel TGFβ1 antagonist.
IMM-H007 improves heart function via reducing cardiac fibrosis
Eur J Pharmacol 2019 Aug 15;857:172442.PMID:31181209DOI:10.1016/j.ejphar.2019.172442.
Cardiac dysfunction is a pathological state characterized by damaged ability of the left ventricle (LV) to either eject or fill blood accompanied by cardiac hypertrophy and fibrosis. IMM-H007, an adenosine derivative, is an activator of AMP-Activated Protein Kinase (AMPK). AMPK can decrease the transforming growth factor-β1 (TGF-β1) expression during fibrosis. Therefore, we hypothesized that IMM-H007 contributed to cardiac dysfunction by mediating cardiac fibrosis. To test this hypothesis, we used angiotensin II (AngII)-induced cardiac remodeling model treated with IMM-H007 or vehicle. Echocardiography measurements showed that IMM-H007 significantly improved heart function indicated by increased LV ejection fraction (%LVEF) and LV fractional shortening (%LVFS). Histological staining and qRT-PCR analysis revealed that IMM-H007 markedly reduced AngII-induced cardiac fibroblast activation (α-smooth muscle actin and periostin) and matrix protein production (Collagen I and Collagen III). However, IMM-H007 did not affect AngII-induced cardiac hypertrophy. Immunoblotting analysis revealed that IMM-H007 activated AMPK, decreased the expression of TGF-β1, and inhibited the activation of Smad2 in heart tissues. In mouse primary cultured cardiac fibroblasts, pharmacological activation of AMPK by IMM-H007 significantly reduced AngII-induced TGF-β1 expression as well. Consistently, in human cardiac fibroblasts-adult ventricular (HCF-av), IMM-H007 activated AMPK and markedly suppressed AngII-induced TGF-β1 expression. These results together reveal that IMM-H007 improves heart function, and alleviates AngII-induced cardiac fibrosis by regulating AMPK-TGF-β1 signaling. These findings suggest IMM-H007 as a potential drug for treating cardiac dysfunction.
Preclinical pharmacokinetic study of a novel lipid-lowering agent, IMM-H007
Eur Rev Med Pharmacol Sci 2020 Nov;24(21):10913.PMID:33215397DOI:10.26355/eurrev_202011_23544.
The article "Preclinical pharmacokinetic study of a novel lipid-lowering agent, IMM-H007, by Z.-L. Zhang, W.-Q. Liu, X.-Z. Deng, published in Eur Rev Med Pharmacol Sci 2018; 22 (24): 8939-8950-DOI: 10.26355/eurrev_201812_16664-PMID: 30575938" has been withdrawn from the authors stating that "after our article was published, we received a conflict of interest from the Chinese Academy of Sciences. They declared that they developed IMM-H007 for the first time and they had already applied for the patent. We had already cited in the references that IMM-H007 came from the Chinese Academy of Sciences. But they still insisted that we had violated their rights. We had to withdraw our paper in order to avoid greater conflicts and disputes". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16664.
IMM-H007, a novel small molecule inhibitor for atherosclerosis, represses endothelium inflammation by regulating the activity of NF-κB and JNK/AP1 signaling
Toxicol Appl Pharmacol 2019 Oct 15;381:114732.PMID:31454633DOI:10.1016/j.taap.2019.114732.
Endothelium inflammation has become a major risk factor for pathological development of atherosclerosis. IMM-H007 (H007), a small molecule compound, is previously reported to reduce inflammatory atherosclerosis. However, the regulatory role of H007 in endothelium inflammation is still unclear. Here, we characterize H007 as a critical repressor in regulation of endothelium inflammation. We find that H007 significantly inhibits monocyte adhesion to endothelial cells and its transendothelial migration. Mechanistically, H007 markedly represses TNFα-induced IκBα degradation and NF-κB nuclear translocation, therefore leading to NF-κB-mediated inflammatory suppression. Moreover, another inflammatory signaling JNK/c-Jun, which is always co-activated with NF-κB in response to pro-inflammatory stimuli, is also found to be restrained by H007 through reducing its phosphorylation status. Thus, we conclude that H007 negatively regulates endothelium inflammation through inactivating NF-κB and JNK/AP1 signaling. More importantly, this study provides us a new insight into understanding the molecular basis by which H007 regulates inflammatory atherosclerosis.
IMM-H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high-fat diet
FEBS Open Bio 2017 Aug 29;7(9):1379-1391.PMID:28904866DOI:10.1002/2211-5463.12272.
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2',3',5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine (IMM-H007) can eliminate hepatic steatosis in hamsters fed a high-fat diet (HFD), as a model of NAFLD. Compared with HFD-only controls, IMM-H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, 1H-MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM-H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM-H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo, IMM-H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM-H007 resolves hepatic steatosis in HFD-fed hamsters by the regulation of lipid metabolism. Thus, IMM-H007 has therapeutic potential for NAFLD.