CMP-5
目录号 : GC39665
CMP-5 是一种有效的选择性 PRMT5 抑制剂，对 PRMT1，PRMT4 和 PRMT7 酶无活性。CMP-5 在组蛋白的准备过程中，通过抑制 PRMT5 甲基转移酶活性选择性地阻断 S2Me-H4R3。CMP-5 阻断 EBV 驱动的 B 淋巴细胞转化，但对正常 B 细胞没有影响。
Cas No.:880813-42-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
CMP-5 is a potent, specific, and selective PRMT5 inhibitor, while displays no activity against PRMT1, PRMT4, and PRMT7 enzymes. CMP-5 selectively blocks S2Me-H4R3 by inhibiting PRMT5 methyltransferase activity on histone preparations. CMP-5 prevents Epstein-Barr virus (EBV)-driven B-lymphocyte transformation but leaving normal B cells unaffected[1][2].
[1]. Alinari L, et al. Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation.Blood. 2015 Apr 16;125(16):2530-43. [2]. Webb LM, et al. PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis. J Immunol. 2017 Feb 15;198(4):1439-1451.
| Cas No. | 880813-42-3 | SDF | |
| Canonical SMILES | CCN1C2=C(C3=C1C=CC=C3)C=C(CNCC4=NC=CC=C4)C=C2 | ||
| 分子式 | C21H21N3 | 分子量 | 315.41 |
| 溶解度 | DMSO: 125 mg/mL (396.31 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 | 3.1705 mL | 15.8524 mL | 31.7048 mL |
| 5 mM | 0.6341 mL | 3.1705 mL | 6.341 mL |
| 10 mM | 0.317 mL | 1.5852 mL | 3.1705 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。
L. pneumophila CMP-5,7-di-N-acetyllegionaminic acid synthetase (LpCLS)-involved chemoenzymatic synthesis of sialosides and analogues
Org Biomol Chem 2020 Jan 28;18(4):738-744.PMID:31912849DOI:10.1039/c9ob02476j.
5,7-Di-N-acetyllegionaminic acid (Leg5,7Ac2) is a bacterial nonulosonic acid (NulO) analogue of sialic acids, an important class of monosaccharides in mammals and in some bacteria. To develop efficient one-pot multienzyme (OPME) glycosylation systems for synthesizing Leg5,7Ac2-glycosides, Legionella pneumophila cytidine 5'-monophosphate (CMP)-Leg5,7Ac2 synthetase (LpCLS) was cloned and characterized. It was successfully used in producing Leg5,7Ac2-glycosides from chemoenzymatically synthesized Leg5,7Ac2 using a one-pot two-enzyme system or from its chemically synthesized six-carbon monosaccharide precursor 2,4-diacetamido-2,4,6-trideoxymannose (6deoxyMan2,4diNAc) in a one-pot three-enzyme system. In addition, LpCLS was shown to tolerate Neu5Ac7NAc, a C9-hydroxyl analogue of Leg5,7Ac2 and also a stable analogue of 7-O-acetylneuraminic acid (Neu5,7Ac2), to allow OPME synthesis of the corresponding α2-3-linked sialosides, from chemically synthesized six-carbon monosaccharide precursor 4-N-acetyl-4-deoxy-N-acetylmannosamine (ManNAc7NAc).
In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals
J Mol Graph Model 2021 Dec;109:108038.PMID:34607208DOI:10.1016/j.jmgm.2021.108038.
The aim of this study is to identify potential drug-like molecules against SARS-CoV-2 virus among the natural antiviral compounds published in the Encyclopedia of Traditional Chinese Medicine. To test inhibition capability of these compounds first, we docked them with Spike protein, angiotensin-converting enzyme 2 (ACE2) (PDB ID: 6M0J) and neuropilin 1 (NRP1) (PDB ID: 7JJC) receptors, and found significant docking scores with extra precision up to -11 kcal/mol. Then, their stability in the binding pockets were further evaluated with molecular dynamics simulation. Eight natural antiviral compounds were identified as potential inhibitors against SARS-CoV-2 cell entry after 200 ns molecular dynamics simulations. We found CMP-3, CMP-4, CMP-5, CMP-6 and CMP-8 are strong binders for the spike protein, CMP-1, CMP-2, CMP-4, CMP-5 and CMP-7 are strong binders for the neuropilin receptor, and CMP-5 is a strong binder for the ACE2. Quercetin derivatives (CMP-4, CMP-5, CMP-6 and CMP-7) were found highly stable in the active domain of NRP1, ACE2 and Spike protein. Especially, CMP-5 showed an inhibitory activity for all targets. These natural antivirals may be potential drug candidates for the prevention of SARS-CoV-2 infection.
Protein arginine methyltransferase 5 (PRMT5) promotes survival of lymphoma cells via activation of WNT/β-catenin and AKT/GSK3β proliferative signaling
J Biol Chem 2019 May 10;294(19):7692-7710.PMID:30885941DOI:10.1074/jbc.RA119.007640.
Epigenetic regulation by the type II protein arginine methyltransferase, PRMT5, plays an essential role in the control of cancer cell proliferation and tumorigenesis. In this report, we investigate the relationship between PRMT5 and WNT/β-CATENIN as well as AKT/GSK3β proliferative signaling in three different types of non-Hodgkin's lymphoma cell lines, clinical samples, and mouse primary lymphoma cells. We show that PRMT5 stimulates WNT/β-CATENIN signaling through direct epigenetic silencing of pathway antagonists, AXIN2 and WIF1, and indirect activation of AKT/GSK3β signaling. PRMT5 inhibition with either shRNA-mediated knockdown or a specific small molecule PRMT5 inhibitor, CMP-5, not only leads to derepression of WNT antagonists and decreased levels of active phospho-AKT (Thr-450 and Ser-473) and inactive phospho-GSK3β (Ser-9) but also results in decreased transcription of WNT/β-CATENIN target genes, CYCLIN D1, c-MYC, and SURVIVIN, and enhanced lymphoma cell death. Furthermore, PRMT5 inhibition leads to reduced recruitment of co-activators CBP, p300, and MLL1, as well as enhanced recruitment of co-repressors HDAC2 and LSD1 to the WNT/β-CATENIN target gene promoters. These results indicate that PRMT5 governs expression of prosurvival genes by promoting WNT/β-CATENIN and AKT/GSK3β proliferative signaling and that its inhibition induces lymphoma cell death, which warrants further clinical evaluation.
Identification of C3b-Binding Small-Molecule Complement Inhibitors Using Cheminformatics
J Immunol 2017 May 1;198(9):3705-3718.PMID:28298523DOI:10.4049/jimmunol.1601932.
The complement system is an elegantly regulated biochemical cascade formed by the collective molecular recognition properties and proteolytic activities of more than two dozen membrane-bound or serum proteins. Complement plays diverse roles in human physiology, such as acting as a sentry against invading microorganisms, priming of the adaptive immune response, and removal of immune complexes. However, dysregulation of complement can serve as a trigger for a wide range of human diseases, which include autoimmune, inflammatory, and degenerative conditions. Despite several potential advantages of modulating complement with small-molecule inhibitors, small-molecule drugs are highly underrepresented in the current complement-directed therapeutics pipeline. In this study, we have employed a cheminformatics drug discovery approach based on the extensive structural and functional knowledge available for the central proteolytic fragment of the cascade, C3b. Using parallel in silico screening methodologies, we identified 45 small molecules that putatively bind C3b near ligand-guided functional hot spots. Surface plasmon resonance experiments resulted in the validation of seven dose-dependent C3b-binding compounds. Competition-based biochemical assays demonstrated the ability of several C3b-binding compounds to interfere with binding of the original C3b ligand that guided their discovery. In vitro assays of complement function identified a single complement inhibitory compound, termed CMP-5, and mechanistic studies of the CMP-5 inhibitory mode revealed it acts at the level of C5 activation. This study has led to the identification of a promising new class of C3b-binding small-molecule complement inhibitors and, to our knowledge, provides the first demonstration of cheminformatics-based, complement-directed drug discovery.
Molecular structures of cytidine-5'-diphosphate and cytidine-5'-diphospho-choline, and their role in intermidiary metabolism
Nature 1975 Dec 11;258(5535):497-501.PMID:172799DOI:10.1038/258497a0.
The nucleotide coenzyme cytidine-5'-diphospho-choline is highly folded. The CMP-5' parts of the molecules in the crystal structure are strongly linked by metal ligation and hydrogen bonds leaving the phosphoryl-choline residues relatively free. Cytidine-5'-diphosphoric acid exists as a zwitterion with N31 protonated. The P-O bond lengths from the anhydride bridging oxygen in the pyrophosphate are significantly different.