D-JNKI-1 (AM-111)
(Synonyms: AM-111; XG-102) 目录号 : GC30057
D-JNKI-1 (AM-111) (AM-111) 是一种高效且可渗透细胞的 JNK 肽抑制剂。
Cas No.:1445179-97-4
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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Animal experiment: | D-JNKI-1 is dissolved in a 0.9% sodium chloride solution for subcutaneous application. Each group (the 1.0% DSS group and the 1.5% DSS group) is randomly subdivided into an intervention group (n = 15) and a control group (n = 15). The mice in the intervention group receive three subcutaneous nuchal administrations of 1 μg/kg D-JNKI-1 on days 2, 12, and 22. The mice in the control group receive physiological saline subcutaneously as a negative control at the same time points in a comparable stress situation. |
References: [1]. Wang J, et al. A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J Neurosci. 2003 Sep 17;23(24):8596-607. | |
D-JNKI-1 is a highly potent and cell-permeable peptide inhibitor of JNK.
D-JNKI-1 (1 μM-1 mM) treatment prevents apoptosis and loss of neomycin-exposed hair cells[1].
D-JNKI-1 (10 μM) prevents nearly all hair cell death and permanent hearing loss induced by neomycin ototoxicity in the scala tympani of the guinea pig cochlea. Local delivery of D-JNKI-1 also prevents acoustic trauma-induced permanent hearing loss in a dose-dependent manner[1]. D-JNKI-1 (0.3 mg/kg, i.p.) reverses these pathological events in the brain mitochondria of the rat and almost completely abolishes cytochrome c release and PARP cleavage[2]. D-JNKI-1 (1 μg/kg, s.c.) results in a significant decrease in the disease activity index, and reduces the expression of CD4+ and CD8+ cells in mice[3].
[1]. Wang J, et al. A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J Neurosci. 2003 Sep 17;23(24):8596-607. [2]. Zhao Y, et al. The JNK inhibitor D-JNKI-1 blocks apoptotic JNK signaling in brain mitochondria. Mol Cell Neurosci. 2012 Mar;49(3):300-10. [3]. Kersting S, et al. The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium. J Inflamm Res. 2013 May 3;6:71-81. [4]. Wang C, et al. Wu-tou decoction attenuates neuropathic pain via suppressing spinal astrocytic IL-1R1/TRAF6/JNK signaling. Oncotarget. 2017 Oct 6;8(54):92864-92879.
| Cas No. | 1445179-97-4 | SDF | |
| 别名 | AM-111; XG-102 | ||
| Canonical SMILES | Asp-Gln-Ser-Arg-Pro-Val-Gln-Pro-Phe-Leu-Asn-Leu-Thr-Thr-Pro-Arg-Lys-Pro-Arg-Pro-Pro-Arg-Arg-Arg-Gln-Arg-Arg-Lys-Lys-Arg-Gly-NH2 | ||
| 分子式 | C164H286N66O40 | 分子量 | 3822.44 |
| 溶解度 | Water : ≥ 50 mg/mL (13.08 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 | 0.2616 mL | 1.3081 mL | 2.6161 mL |
| 5 mM | 0.0523 mL | 0.2616 mL | 0.5232 mL |
| 10 mM | 0.0262 mL | 0.1308 mL | 0.2616 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111)
Hear Res 2018 Oct;368:86-91.29573879 10.1016/j.heares.2018.03.003
There is a growing interest in the auditory community to develop novel prophylactic and therapeutic drugs to prevent permanent sensorineural hearing loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK) pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has shown promise as both a prophylactic and therapeutic agent for acute cochlear injury. A number of pre-clinical and clinical studies have determined the impact of D-JNKI-1 on acute sensorineural hearing loss. Given the inner-ear selective therapeutic profile, local route of administration, and ability to diffuse across cellular membranes rapidly using both active and passive transport makes D-JNK-1 a promising oto-protective drug. In this review article, we discuss the application of D-JNKI-1 in various auditory disorders as well as its pharmacological properties and distribution in the cochlea.
The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells
Front Mol Neurosci 2022 Mar 11;15:824762.35359571 PMC8963355
Aminoglycosides can cause ototoxicity and lead to hair cell damage. Neomycin-induced ototoxicity is related to increased production of reactive oxygen species (ROS) and triggering hair cell apoptosis. The c-Jun-N-terminal kinase (JNK) pathway plays an essential role during hair cell damage. This study was designed to investigate an inhibitor of JNK, D-JNKI-1 (AM-111/brimapitide) in neomycin-induced HEI-OC1 cell apoptosis. The results demonstrate that neomycin increased intracellular ROS accumulation, which induces apoptosis. D-JNKI-1 decreased neomycin-induced ROS generation, reduced caspase-8 and cleavage of caspase-3 expression, sustained JNK activation and AMPK and p38 phosphorylation, downregulated Bax, and upregulated Bcl-2. Together, D-JNKI-1 plays an essential role in protecting against neomycin-induced HEI-OC1 cell apoptosis by suppressing ROS generation, which inhibited JNK activation and AMPK and p38 phosphorylation to ameliorate JNK-mediated HEI-OC1 cell apoptosis.
D-JNKI-1 treatment prevents the progression of hearing loss in a model of cochlear implantation trauma
Otol Neurotol 2006 Jun;27(4):504-11.16791042 10.1097/01.mao.0000217354.88710.13
Hypotheses: 1) Hearing loss caused by electrode insertion trauma has both acute and delayed components; and 2) the delayed component of trauma-initiated hearing loss can be prevented by a direct delivery of a peptide inhibitor of the c-Jun N-terminal kinase cell death signal cascade, that is, D-JNKI-1, immediately after the electrode insertion within the cochlea. Background: Acute trauma to the macroscopic elements of the cochlea from electrode insertion is well known. The impact of trauma-induced oxidative stress within injured cochlear tissues and the efficacy of drugs (e.g., D-JNKI-1) to prevent apoptosis of damaged hair cells is not well defined. Methods: Hearing function was tested by pure-tone evoked auditory brainstem responses (ABRs) and distortion products of otoacoustic emissions (DPOAEs). D-JNKI-1 in artificial perilymph (AP) or AP alone was delivered into the scala tympani immediately after electrode trauma and for 7 days. Controls were nontreated contralateral and D-JNKI-1-treated ears without electrode insertion trauma. Results: There was no increase in the hearing thresholds of either the contralateral control ears or in the D-JNKI-1 without trauma animals. There was a progressive increase in ABR thresholds and decrease in DPOAE amplitudes after electrode insertion trauma in untreated and in AP-treated cochleae. Treatment with D-JNKI-1 prevented the progressive increase in ABR thresholds and decrease in DPOAE amplitudes that occur after electrode insertion trauma. Conclusion: Hearing loss caused by cochlear implant electrode insertion trauma in guinea pigs has both acute and delayed components. The delayed component can be prevented by treating the cochlea with D-JNKI-1.
The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium
J Inflamm Res 2013 May 3;6:71-81.23667316 PMC3650567
Purpose: The c-Jun N-terminal kinases (JNK) are involved in the activation of T cells and the synthesis of proinflammatory cytokines. Several studies have established the relevance of the JNK pathway in inflammatory bowel diseases. The present study analyzed the therapeutic effect of D-JNKI-1, a specific JNK-inhibiting peptide, in a low-dose dextran sulfate sodium (DSS) model of chronic colitis. Methods: DSS colitis was induced in female C57/BL6 mice by cyclic administration using different concentrations of DSS (1.0% and 1.5%). Mice in the intervention groups received subcutaneous administration of 1 μg/kg D-JNKI-1 on days 2, 12, and 22. They were monitored daily to assess the severity of colitis, body weight, stool consistency, and the occurrence of occult blood or gross rectal bleeding using evaluation of the disease activity index. The animals were sacrificed after 30 days, and the inflamed intestine was histologically evaluated using a crypt damage score. Immunohistochemical quantification of CD4(+) and CD8(+) cells was also carried out. Results: Administration of 1 μg/kg D-JNKI-1 resulted in a significant decrease in the disease activity index (P = 0.013 for 1.0% DSS; P = 0.007 for 1.5% DSS). As a mild form of colitis was induced, histological examination did not show any distinct damage to the mucosa and crypts. However, expression of CD4(+) and CD8(+) cells was reduced in mice treated with D-JNKI-1 (not significant). Conclusion: Administration of D-JNKI-1 resulted in a clinical attenuation of chronic DSS colitis, and a therapeutic effect of D-JNKI-1 must therefore be assumed. The decrease in CD4(+) and CD8(+) cells may reflect the influence of D-JNKI-1 on T-cell activation, differentiation, and migration.
The JNK inhibitor D-JNKI-1 blocks apoptotic JNK signaling in brain mitochondria
Mol Cell Neurosci 2012 Mar;49(3):300-10.22206897 10.1016/j.mcn.2011.12.005
Kainic acid (KA) induced seizures provokes an extensive neuronal degeneration initiated by c-Jun N-terminal kinases (JNK) as central mediators of excitotoxicity. However, the actions of their individual isoforms in cellular organelles including mitochondria remain to be elucidated. Here, we have studied the activation of JNK1, JNK2 and JNK3 and their activators, mitogen-activated protein kinase kinase (MKK) 4/7, in brain mitochondria, cytosolic and nuclear fractions after KA seizures. In the mitochondrial fraction, KA significantly increased the presence of JNK1, JNK3 and MKK4 and stimulated their phosphorylation i.e. activation. The pro-apoptotic proteins, Bim and Bax were induced and, consequently, the ratio Bcl-2-Bax decreased. These changes were paralleled by the release of cytochrome c and cleavage of poly(ADP-ribose)-polymerase (PARP). The JNK peptide inhibitor, D-JNKI-1 (XG-102) reversed these pathological events in the mitochondria and almost completely abolished cytochrome c release and PARP cleavage. Importantly, JNK3, but not JNK1 or JNK2, was associated with Bim in mitochondria and D-JNKI-1 prevented the formation of this apoptotic complex. Apart from of the attenuation of c-Jun phosphorylation in the nucleus, D-JNKI-1 did not affect the level of JNK3 isoform in the nuclear and cytosolic fractions. These findings provide novel insights into the mode of action of individual JNK isoforms in cell organelles and points to the JNK3 pool in mitochondria as a target of the JNK inhibitor D-JNKI-1 to confer neuroprotection.