MT1
目录号 : GC61097
MT1是BETbromodomains的化学探针，其对BRD4(1)的IC50值为0.789nM。
Cas No.:2060573-82-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
MT1 is a bivalent chemical probe of BET bromodomains, with an IC50 of 0.789 nM for BRD4(1)[1].
MT1 (100 nM, 24 h) significantly induces apoptosis via caspase-3 and PARP in MV4;11 cells[1]. Western Blot Analysis[1] Cell Line: MV4;11 cells[1].
MT1 (44.2 and 22.1 µmol/kg, ip daily, for 14 days) significantly delayed leukemia progression in mice (Mus musculus) compared to JQ1[1].MT1 exhibits terminal t1/2 of 2.70 h in mice[1]. Animal Model: Leukemia xenograft models[1].
[1]. Minoru Tanaka, et al. Design and characterization of bivalent BET inhibitors. Nat Chem Biol. 2016 Dec;12(12):1089-1096.
| Cas No. | 2060573-82-0 | SDF | |
| Canonical SMILES | CC1=NN=C2N1C3=C(C(C4=CC=C(C=C4)Cl)=N[C@H]2CC(NCCOCCOCCOCCOCCOCCOCCOCCNC(C[C@@H]5N=C(C6=C(N7C5=NN=C7C)SC(C)=C6C)C8=CC=C(C=C8)Cl)=O)=O)C(C)=C(C)S3 | ||
| 分子式 | C54H66Cl2N10O9S2 | 分子量 | 1134.2 |
| 溶解度 | DMSO: 150 mg/mL (132.25 mM); Water: < 0.1 mg/mL (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 | 0.8817 mL | 4.4084 mL | 8.8168 mL |
| 5 mM | 0.1763 mL | 0.8817 mL | 1.7634 mL |
| 10 mM | 0.0882 mL | 0.4408 mL | 0.8817 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。
Microglial MT1 activation inhibits LPS-induced neuroinflammation via regulation of metabolic reprogramming
Aging Cell 2021 Jun;20(6):e13375.PMID:33964119DOI:10.1111/acel.13375.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Although its pathogenesis remains unclear, a number of studies indicate that microglia-mediated neuroinflammation makes a great contribution to the pathogenesis of PD. Melatonin receptor 1 (MT1) is widely expressed in glia cells and neurons in substantia nigra (SN). Neuronal MT1 is a neuroprotective factor, but it remains largely unknown whether dysfunction of microglial MT1 is involved in the PD pathogenesis. Here, we found that MT1 was reduced in microglia of SN in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Microglial MT1 activation dramatically inhibited lipopolysaccharide (LPS)-induced neuroinflammation, whereas loss of microglial MT1 aggravated it. Metabolic reprogramming of microglia was found to contribute to the anti-inflammatory effects of MT1 activation. LPS-induced excessive aerobic glycolysis and impaired oxidative phosphorylation (OXPHOS) could be reversed by microglial MT1 activation. MT1 positively regulated pyruvate dehydrogenase alpha 1 (PDHA1) expression to enhance OXPHOS and suppress aerobic glycolysis. Furthermore, in LPS-treated microglia, MT1 activation decreased the toxicity of conditioned media to the dopaminergic (DA) cell line MES23.5. Most importantly, the anti-inflammatory effects of MT1 activation were observed in LPS-stimulated mouse model. In general, our study demonstrates that MT1 activation inhibits LPS-induced microglial activation through regulating its metabolic reprogramming, which provides a mechanistic insight for microglial MT1 in anti-inflammation.
Fetal liver mesenchymal stem cells restore ovarian function in premature ovarian insufficiency by targeting MT1
Stem Cell Res Ther 2019 Nov 29;10(1):362.PMID:31783916DOI:10.1186/s13287-019-1490-8.
Background: With the development of regenerative medicine and tissue engineering technology, almost all stem cell therapy is efficacious for the treatment of premature ovarian failure (POF) or premature ovarian insufficiency (POI) animal models, whereas little stem cell therapy has been practiced in clinical settings. The underlying molecular mechanism and safety of stem cell treatment in POI are not fully understood. In this study, we explored whether fetal mesenchymal stem cells (fMSCs) from the liver restore ovarian function and whether melatonin membrane receptor 1 (MT1) acts as a regulator for treating POI disease. Methods: We designed an in vivo model (chemotherapy-induced ovary damage) and an in vitro model (human ovarian granulosa cells (hGCs)) to understand the efficacy and molecular cues of fMSC treatment of POI. Follicle development was observed by H&E staining. The concentration of sex hormones in serum (E2, AMH, and FSH) and the concentration of oxidative and antioxidative metabolites and the enzymes MDA, SOD, CAT, LDH, GR, and GPx were measured by ELISA. Flow cytometry (FACS) was employed to detect the percentages of ROS and proliferation rates. mRNA and protein expression of antiapoptotic genes (SURVIVIN and BCL2), apoptotic genes (CASPASE-3 and CASPASE-9), and MT1 and its downstream genes (JNK1, PCNA, AMPK) were tested by qPCR and western blotting. MT1 siRNA and related antagonists were used to assess the mechanism. Results: fMSC treatment prevented cyclophosphamide (CTX)-induced follicle loss and recovered sex hormone levels. Additionally, fMSCs significantly decreased oxidative damage, increased oxidative protection, improved antiapoptotic effects, and inhibited apoptotic genes in vivo and in vitro. Furthermore, fMSCs also upregulated MT1, JNK1, PCNA, and AMPK at the mRNA and protein levels. With MT1 knockdown or antagonist treatment in normal hGCs, the protein expression of JNK1, PCNA, and AMPK and the percentage of proliferation were impaired. Conclusions: fMSCs might play a crucial role in mediating follicular development in the POI mouse model and stimulating the activity of POI hGCs by targeting MT1.
Melatonergic Receptors (MT1/Mt2) as a Potential Additional Target of Novel Drugs for Depression
Neurochem Res 2022 Oct;47(10):2909-2924.PMID:35689787DOI:10.1007/s11064-022-03646-5.
A complex pathogenesis involving several physiological systems is theorized to underline the development of depressive disorders. Depression is accompanied by circadian regulation disruption and interaction with the functioning of both central and peripheral oscillators. Many aspects of melatonin function unite these systems. The use of drugs for circadian rhythm disorders could inspire a potential treatment strategy for depression. Melatonin plays an essential role in the regulation of circadian rhythms. It exerts effect by activating two types of melatonin receptors, type 1A (MT1) and 1B (MT2). These are G-protein-coupled receptors, predominantly located in the central nervous system. MT1/MT2 agonists could be a useful treatment approach according to all three prevalent theories of the pathogenesis of depression involving either monoamines, synaptic remodeling, or immune/inflammatory events. MT1/MT2 receptors can be a potential target for novel antidepressants with impact on concentrations of neurotrophins or neurotransmitters, and reducing levels of pro-inflammatory cytokines. There is an interesting cross-talk mediated via the physical association of melatonin and serotonin receptors into functional heteromers. The antidepressive and neurogenetic effects of MT1/MT2 agonists can also be caused by the inhibition of the acid sphingomyelinase, leading to reduced ceramide, or increasing monoamine oxidase A levels in the hippocampus. Compounds targeting MT1 and MT2 receptors could have potential for new anti-depressants that may improve the quality of therapeutic interventions in treating depression and relieving symptoms. In particular, a combined effect on MT1 and/or MT2 receptors and neurotransmitter systems may be useful, since the normalization of the circadian rhythm through the melatonergic system will probably contribute to improved treatment. In this review, we discuss melatonergic receptors as a potential additional target for novel drugs for depression.
MT1 Melatonin Receptor Reconstitution in Nanodiscs
Methods Mol Biol 2022;2550:171-178.PMID:36180690DOI:10.1007/978-1-0716-2593-4_21.
A way to study G protein-coupled receptors in a minimal system is to reconstruct artificial membrane mimics, made of detergent and/or of lipids in which the purified receptor is maintained. In particular, it is now possible to generate lipid nanoparticles, such as nanodiscs, in which a single receptor molecule is included. Such objects offer the invaluable potential of studying an isolated receptor stabilized in a finely controlled membrane-like environment to evaluate its pharmacology, its function, and its structure at the molecular level. In this chapter, we detail the different steps from the extraction and isolation of a recombinant MT1 melatonin receptor in detergent, down to its reconstitution into nanodiscs. A G protein activation test is further described in order to exemplify how the functionality of such particles may be investigated.
MT1 Receptor Signaling Pathways by Impedance Measurement
Methods Mol Biol 2022;2550:201-206.PMID:36180694DOI:10.1007/978-1-0716-2593-4_25.
Melatonin exerts its classical effects of relay of the circadian rhythm through two G protein-coupled receptors, MT1 and MT2. The functions attributed to melatonin are so numerous that the action of this neurohormone should be through several protein targets or through new coupled biochemistry routes at its receptors. In order to better explore and understand these melatonin-dependent activities, we enlarged the functional pathways linked to the activation of the receptors in living system. Impedance has been shown to rely on the shape-shifting capacity of receptor-associated mechanisms. Those changes elicited by an agonist lead to changes in the actual shape of the cells, and thus to their electric conductivity. The impact of those changes onto the physiology of the cells is not completely understood from a mechanistic point of view, but the measure of these changes associated with various ligands at the melatonin receptor(s) might bring new information on melatonin-dependent cell reactivity. The following chapter is a detailed account of the way impedance can be measured in MT1-experssing cells.