S26131
目录号 : GC38844
S26131 (compound 5) 是一种高效、选择性的 MT1 褪黑激素配体。对 MT1 和 MT2 的 Ki 值分别为 0.5 和 112 nM。S26131 表现为 MT1 和 MT2 拮抗剂。
Cas No.:296280-56-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
S26131 (compound 5) is a potent and selective MT1 melatoninergic ligand, and the Ki values are 0.5 and 112 nM for MT1 and MT2, respectively. S26131 behaves as an MT1 and MT2 antagonist[1].
S26131 behaves as an antagonist on MT1 and MT2 receptors with KB values of 5.32 and 143 nM, respectively[1].
[1]. Descamps-FranÇois C, et al. Design and synthesis of naphthalenic dimers as selective MT1 melatoninergic ligands. J Med Chem. 2003 Mar 27;46(7):1127-9.
| Cas No. | 296280-56-3 | SDF | |
| Canonical SMILES | CC(NCCC1=C2C=C(C=CC2=CC=C1)OCCCOC3=CC=C4C=CC=C(C4=C3)CCNC(C)=O)=O | ||
| 分子式 | C31H34N2O4 | 分子量 | 498.61 |
| 溶解度 | DMSO: 5 mg/mL (10.03 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 | 2.0056 mL | 10.0279 mL | 20.0558 mL |
| 5 mM | 0.4011 mL | 2.0056 mL | 4.0112 mL |
| 10 mM | 0.2006 mL | 1.0028 mL | 2.0056 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。
Melatonin inhibits muscular-mucosal stretch-sensitive bladder afferents via the MT2 receptors
Sci Rep 2022 Oct 21;12(1):17686.PMID:36271291DOI:10.1038/s41598-022-22705-z.
Melatonin is a circadian rhythm regulator capable of controlling a variety of physiological processes in the body. It predominantly acts via the melatonin 1 (MT1) and MT2 receptors expressed in the CNS neurons and peripheral organs and tissues. Melatonin can modulate urinary bladder function, however, to date it is not known if melatonin can regulate activity of sensory neurons innervating the bladder. Bladder afferents play an important role in urine storage and voiding. Therefore, this study aims to determine if melatonin can regulate mechanosensitivity of 2 major classes of sensory neurons in the guinea pig bladder: stretch-insensitive mucosal and low threshold stretch-sensitive muscular-mucosal afferents. The effects of melatonin on the mechanosensitivity of mucosal and muscular-mucosal afferents were measured ex vivo using single unit extracellular recording. Melatonin did not affect the responses of mucosal afferents to stroking of their receptive fields but did concentration-dependently, significantly inhibit 69% of muscular-mucosal afferents responses to stroking and bladder stretch. This inhibitory effect was not affected by the MT1 receptor antagonist, S26131 but was blocked by the selective MT2 receptor antagonists, K-185 and 4-P-PDOT. Forskolin significantly potentiated the responses of muscular-mucosal afferents to stroking and stretch, which were prevented by melatonin. These findings demonstrate a direct inhibitory effect of melatonin on the mechanosensitivity of low threshold stretch-sensitive muscular-mucosal bladder afferents acting via MT2 receptors, which is independent from its action on detrusor muscle. This may have important clinical implications for the treatment of many common bladder disorders including nocturia.
Melatonin promotes the proliferation of primordial germ cell-like cells derived from porcine skin-derived stem cells: A mechanistic analysis
J Pineal Res 2022 Nov;73(4):e12833.PMID:36106819DOI:10.1111/jpi.12833.
In vitro differentiation of stem cells into functional gametes remains of great interest in the biomedical field. Skin-derived stem cells (SDSCs) are an adult stem cells that provides a wide range of clinical applications without inherent ethical restrictions. In this paper, porcine SDSCs were successfully differentiated into primordial germ cell-like cells (PGCLCs) in conditioned media. The PGCLCs were characterized in terms of cell morphology, marker gene expression, and epigenetic properties. Furthermore, we also found that 25 μM melatonin (MLT) significantly increased the proliferation of the SDSC-derived PGCLCs while acting through the MLT receptor type 1 (MT1). RNA-seq results found the mitogen-activated protein kinase (MAPK) signaling pathway was more active when PGCLCs were cultured with MLT. Moreover, the effect of MLT was attenuated by the use of S26131 (MT1 antagonist), crenolanib (platelet-derived growth factor receptor inhibitor), U0126 (mitogen-activated protein kinase kinase inhibitor), or CCG-1423 (serum response factor transcription inhibitor), suggesting that MLT promotes the proliferation processes through the MAPK pathway. Taken together, this study highlights the role of MLT in promoting PGCLCs proliferation. Importantly, this study provides a suitable in vitro model for use in translational studies and could help to answer numerous remaining questions related to germ cell physiology.
Melatonin reduces neuropathic pain behavior and glial activation through MT2 melatonin receptor modulation in a rat model of lysophosphatidylcholine-induced demyelination neuropathy
Neurochem Int 2020 Nov;140:104827.PMID:32853748DOI:10.1016/j.neuint.2020.104827.
In this study, we investigated whether melatonin treatment prevents development of neuropathic pain via suppression of glial mitogen-activated protein kinases (MAPKs) activation in the cuneate nucleus (CN) in a lysophosphatidylcholine (LPC)-induced median nerve demyelination neuropathy model. Rats were fed orally with melatonin once a day at a dose of 37.5, 75, or 150 mg/kg 30 min before until 3 days after LPC treatment. Subsequently, behavioral tests were conducted on these animals, and immunohistochemistry and immunoblotting were used for qualitative and quantitative analysis of glia and MAPKs, including ERK, JNK, and p38, activation. Enzyme-linked immunosorbent assays were applied to measure pro-inflammatory cytokine responses. Furthermore, intra-CN microinjection of S26131 (MT1 receptor antagonist), 4P-PDOT (MT2 receptor antagonist), or prazosin (MT3 receptor antagonist) were performed to investigate the association between melatonin receptor subtypes and effects of melatonin on demyelination neuropathy. LPC treatment of the median nerve induced a significant increase in glial fibrillary acidic protein (GFAP; an astrocyte marker) and ED1 (an activated microglia marker) immunoreactivity in the ipsilateral CN and led to development of neuropathic pain behavior. Inspection of GFAP-immunoreactive astrocytes revealed that astrocytic hypertrophy, but not proliferation, contributed to increased GFAP immunoreactivity. Double immunofluorescence showed that both GFAP-immunoreactive astrocytes and ED1-immunoreactive microglia co-expressed p-ERK, p-JNK, and p-p38 immunoreactivity. Melatonin administration dose-dependently reduced neuropathic pain behavior, decreased glial and MAPKs activation, and diminished the release of pro-inflammatory cytokines in the ipsilateral CN after LPC treatment. Furthermore, 4P-PDOT, but not S26131 or prazosin, antagonized the therapeutic effects of melatonin. In conclusion, administration of melatonin, via its cognate MT2 receptor, inhibited activation of glial MAPKs, production of pro-inflammatory cytokines, and development of demyelination-induced neuropathic pain behavior.