J-2156
(Synonyms: J-2156) 目录号 : GC36358
J-2156 是一种高效，选择性的生长抑素受体 4 型 (SST4 受体) 激动剂，对于人和大鼠 SST4 受体的 IC50 分别为 0.05 nM 和 0.07 nM[1]。 J-2156 用于缓解大鼠同侧后爪的机械性异常性疼痛和机械性痛觉过敏的 ED50 分别为 3.7 mg/kg 和 8.0 mg/kg。
Cas No.:848647-56-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
J-2156 is a high potent, selective somatostatin receptor type 4 (SST4 receptor) agonist with IC50s of 0.05 nM and 0.07 nM for human and rat SST4 receptors, respectively. The ED50 of J-2156 in rats for the relief of mechanical allodynia and mechanical hyperalgesia in the ipsilateral hindpaws was 3.7 and 8.0 mg/kg, respectively[1]. IC50: 0.05 nM (human SST4) and 0.07 nM (rat SST4)[1]
J-2156 (1-10mg/kg; i.p.; for 3 hours) of single bolus doses has anti-allodynic effect on ipsilateral and contralateral in BCIBP-rats[1]. Animal Model: BCIBP-rats[1]
[1]. Shenoy PA, et al. The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain. Front Pharmacol. 2018 May 15;9:495.
| Cas No. | 848647-56-3 | SDF | |
| 别名 | J-2156 | ||
| Canonical SMILES | O=C(N)[C@@H](NC([C@H](CCN)NS(C1=CC=C(C)C2=CC=CC=C21)(=O)=O)=O)CC3=CC=CC=C3 | ||
| 分子式 | C24H28N4O4S | 分子量 | 468.57 |
| 溶解度 | DMSO : 250 mg/mL (533.54 mM; Need ultrasonic) | 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 | 2.1342 mL | 10.6708 mL | 21.3415 mL |
| 5 mM | 0.4268 mL | 2.1342 mL | 4.2683 mL |
| 10 mM | 0.2134 mL | 1.0671 mL | 2.1342 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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J-2156, a somatostatin receptor type 4 agonist, alleviates mechanical hyperalgesia in a rat model of chronic low back pain
Biomed Pharmacother 2019 Sep;117:109056.PMID:31181441DOI:10.1016/j.biopha.2019.109056.
Chronic low back pain (LBP) ranks among the most common reasons for patient visits to healthcare providers. Drug treatments often provide only partial pain relief and are associated with considerable side-effects. J-2156 [(1'S,2S)-4amino-N-(1'-carbamoyl-2'-phenylethyl)-2-(4"-methyl-1"-naphthalenesulfonylamino)butanamide] is an agonist that binds with nanomolar affinity to the rat and human somatostatin receptor type 4 (SST4 receptor). Hence, our aim was to assess the efficacy of J-2156 for relief of chronic mechanical LBP in a rat model. Male Sprague Dawley rats were anaesthetised and their lumbar L4/L5 and L5/L6 intervertebral discs (IVDs) were punctured (0.5 mm outer diameter, 2 mm-deep) 10 times per disc. Sham-rats underwent similar surgery, but without disc puncture. For LBP-rats, noxious pressure hyperalgesia developed in the lumbar axial deep tissues from day 7 to day 21 post-surgery, which was maintained until study completion. Importantly, mechanical hyperalgesia did not develop in the lumbar axial deep tissues of sham-rats. In LBP-rats, single intraperitoneal (i.p.) injection of J-2156 (3, 10, 30 mg kg-1) alleviated primary and secondary hyperalgesia in the lumbar axial deep tissues at L4/L5 and L1, respectively. This was accompanied by a reduction in the otherwise augmented lumbar (L4-L6) dorsal root ganglia expression levels of the pro-nociceptive mediators: phosphorylated p38 (pp38) mitogen-activated protein kinase (MAPK) and phosphorylated p44/p42 MAPK and a reduction in pp38 MAPK in the lumbar enlargement of the spinal cord. The SST4 receptor is worthy of further investigation as a target for discovery of novel analgesics for the relief of chronic LBP.
The somatostatin receptor 4 agonist J-2156 reduces mechanosensitivity of peripheral nerve afferents and spinal neurons in an inflammatory pain model
Eur J Pharmacol 2015 Jan 5;746:274-81.PMID:25445035DOI:10.1016/j.ejphar.2014.11.003.
Somatostatin (SST) is a peptide hormone that regulates the endocrine system and affects neurotransmission via interaction with G protein-coupled SST receptors and inhibition of the release of different hormones. The aim of this study was to investigate whether the analgesic properties of the selective SSTR4 agonist J-2156 are mediated via peripheral and/or spinal receptors. Effect on mechanical hyperalgesia in the Complete Freund׳s Adjuvant (CFA) model was measured after intraperitoneal application of J-2156. Electrophysiological neuronal recordings were conducted 24 h after injection of CFA or vehicle into the paw of Wistar rats. Mechanosensitivity of peripheral afferents of the saphenous nerve as well as of spinal wide dynamic range (WDR) and nociceptive-specific (NS) neurons were measured after systemic or spinal application of J-2156. In CFA animals J-2156 dose dependently reduced hyperalgesia in behavioral studies. The minimal effective dose was 0.1 mg/kg. Mechanosensitivity of peripheral afferents and spinal neurons was significantly reduced by J-2156. NS neurons were dose dependently inhibited by J-2156 while in WDR neurons only the highest concentration of 100 µM had an effect. In sham controls, J-2156 had no effect on neuronal activity. We demonstrated that J-2156 dose-dependently reduces peripheral and spinal neuronal excitability in the CFA rat model without affecting physiological pain transmission. Given the high concentration of the compound required to inhibit spinal neurons, it is unlikely that the behavioral effect seen in CFA model is mediated centrally. Overall these data demonstrated that the analgesic effect of J-2156 is mediated mainly via peripheral SST4 receptors.
The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain
Front Pharmacol 2018 May 15;9:495.PMID:29867498DOI:10.3389/fphar.2018.00495.
In the majority of patients with breast cancer in the advanced stages, skeletal metastases are common, which may cause excruciating pain. Currently available drug treatments for relief of breast cancer-induced bone pain (BCIBP) include non-steroidal anti-inflammatory drugs and strong opioid analgesics along with inhibitors of osteoclast activity such as bisphosphonates and monoclonal antibodies such as denosumab. However, these medications often lack efficacy and/or they may produce serious dose-limiting side effects. In the present study, we show that J-2156, a somatostatin receptor type 4 (SST4 receptor) selective agonist, reverses pain-like behaviors in a rat model of BCIBP induced by unilateral intra-tibial injection of Walker 256 breast cancer cells. Following intraperitoneal administration, the ED50 of J-2156 for the relief of mechanical allodynia and mechanical hyperalgesia in the ipsilateral hindpaws was 3.7 and 8.0 mg/kg, respectively. Importantly, the vast majority of somatosensory neurons in the dorsal root ganglia including small diameter C-fibers and medium-large diameter fibers, that play a crucial role in cancer pain hypersensitivities, expressed the SST4 receptor. J-2156 mediated pain relief in BCIBP-rats was confirmed by observations of a reduction in the levels of phosphorylated extracellular signal-regulated kinase (pERK), a protein essential for central sensitization and persistent pain, in the spinal dorsal horn. Our results demonstrate the potential of the SST4 receptor as a pharmacological target for relief of BCIBP and we anticipate the present work to be a starting point for further mechanism-based studies.
Assessment of the anti-hyperalgesic efficacy of J-2156, relative to clinically available analgesic/adjuvant agents in a rat model of mild to moderate chronic mechanical low back pain (LBP)
Clin Exp Pharmacol Physiol 2020 Dec;47(12):1912-1922.PMID:32686129DOI:10.1111/1440-1681.13383.
Chronic mechanical low back pain (cLBP) is a leading cause of disability and a major socio-economic burden internationally. The lifetime prevalence of non-specific LBP is approximately 84%, with the prevalence of cLBP at about 23%. Clinically available analgesic/adjuvant medications often provide inadequate pain relief in patients experiencing cLBP. Hence, the urgency for discovery of effective and better tolerated medications. Fourteen days after the induction of five shallow annular punctures (5X) in the lumbar intervertebral discs at L4/L5 and L5/L6 in male Sprague-Dawley rats, mechanical hyperalgesia was fully developed in the lumbar axial deep tissues at L4/L5 (primary) and L1 (secondary). Importantly, mechanical allodynia in the hindpaws was absent. From day 28, we assessed the face validity of our mild to moderate LBP-5X rat model using four clinically available analgesic/adjuvant drugs, namely gabapentin, morphine, meloxicam and amitriptyline relative to vehicle. Additionally, the anti-hyperalgesic effects of J-2156, a highly selective small molecule somatostatin type 4 receptor agonist was assessed. Single i.p. bolus doses of gabapentin and meloxicam at the highest doses tested (100 and 30 mg/kg, respectively) alleviated secondary hyperalgesia (L1) but not primary hyperalgesia (L4/5). Morphine at 1 mg/kg alleviated both primary and secondary hyperalgesia in these tissues, whereas amitriptyline at the doses tested, lacked efficacy. These findings attest to the face validity of our model. J-2156 at 10 and 30 mg/kg alleviated secondary hyperalgesia in the lumbar axial deep tissues at L1 with a non-significant trend for relief of primary hyperalgesia in the corresponding tissues at L4/L5 in these animals.
Analgesic effects of the somatostatin sst4 receptor selective agonist J-2156 in acute and chronic pain models
Eur J Pharmacol 2006 Jun 6;539(1-2):71-5.PMID:16697366DOI:10.1016/j.ejphar.2006.03.082.
Somatostatin released from capsaicin-sensitive afferents exerts systemic anti-nociceptive actions, presumably via somatostatin receptor subtype 4 (sst4). In the present study, the antinociceptive effects of a novel somatostatin sst4 receptor selective peptidomimetic compound, J-2156 (1-100 microg/kg i.p.), were examined. J-2156 inhibited nocifensive behaviour of mice in the second phase of the formalin test. Adjuvant-evoked chronic inflammatory mechanical allodynia was decreased in rats treated with J-2156 for 21 days. Sciatic nerve ligation-induced neuropathic mechanical hyperalgesia was inhibited by J-2156 on the seventh postoperative day. Results obtained using this highly selective agonist suggest that somatostatin sst4 receptors represent a promising target for new perspectives in analgesic therapy.