X77
目录号 : GC62512
X77 是 SARS-CoV-2 蛋白酶 (SARS-CoV-2 Mpro) 的有效非共价键抑制剂。X77 与 SARS-CoV-2 Mpro结合的 Kd 值为 0.057 μM。
Cas No.:2455518-33-7
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
X77 is a potent non-covalent inhibitor of the main protease of SARS-CoV-2 (SARS-CoV-2 Mpro)[1]. X77 binds to SARS-CoV-2 Mpro with a Kd value of 0.057 μM[2].
X77 can bind to SARS-CoV-2 Mpro (PDB code: 6W63). SARS-CoV-2 Mpro (PDB code: 6W63) is the main protease of SARS-CoV-2 and is one of the most important drug targets among coronaviruses[1].
[1]. Sohini Chakraborti, et al. Drug Repurposing Approach Targeted Against Main Protease of SARS-CoV-2 Exploiting ’Neighbourhood Behaviour’ in 3D Protein Structural Space and 2D Chemical Space of Small Molecules.
[2]. Alexander M Andrianov, et al. Computational discovery of small drug-like compounds as potential inhibitors of SARS-CoV-2 main protease. J Biomol Struct Dyn
| Cas No. | 2455518-33-7 | SDF | |
| 分子式 | C27H33N5O2 | 分子量 | 459.58 |
| 溶解度 | 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 | 2.1759 mL | 10.8795 mL | 21.759 mL |
| 5 mM | 0.4352 mL | 2.1759 mL | 4.3518 mL |
| 10 mM | 0.2176 mL | 1.0879 mL | 2.1759 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。
Molecular Docking Studies of Bioactive Nicotiflorin against 6W63 Novel Coronavirus 2019 (COVID-19)
Comb Chem High Throughput Screen 2021;24(6):874-878.PMID:33109057DOI:10.2174/1386207323999200820162551.
Background: COVID-19 which is known as the novel coronavirus was reported in December 2019 in Wuhan city, China and many people have been contaminated by environmental contamination and transmission from one human to another until now. Objective: The objective of the present work is to establish the inhibitory potential of nicotiflorin, a Kaempferol 3-O-rutinoside flavonoid, against the deadly coronavirus (COVID-19) 6W63 (main protease 3Clpro protein), using molecular docking approach. Methods: The Molegro Virtual Docker software (MVD) with a 30 Å grid resolution was used. The structure was drawn by Chem 3D software and energy minimization was done by the MM2 force field. The protein 6W63 was downloaded from the protein data bank. Molegro modeller was used for score calculations. Result: The molecular docking studies were carried out on nicotiflorin and standard inhibitor X77, where standard inhibitor was observed in a co-crystallized state with main protease 3Clpro protein 6W63. The MolDock score, Rerank Sore, and H Bond score of nicotiflorin and standard inhibitor X77 were observed as -173.058, -127.302, -21.9398 and -156.913,-121.296,-5.7369, respectively. Conclusion: Molecular docking studies have confirmed that the affinity of flavonoid nicotiflorin with the amino acids of the viral protein 6W63 was relatively more than the standard X77. For the effective treatment of novel coronavirus COVID-19, the effectiveness of the identified flavonoid nicotiflorin can further be evaluated for safety and efficacy parameters at both preclinical and clinical stages.
Computational discovery of small drug-like compounds as potential inhibitors of SARS-CoV-2 main protease
J Biomol Struct Dyn 2021 Sep;39(15):5779-5791.PMID:32662333DOI:10.1080/07391102.2020.1792989.
A computational approach to in silico drug discovery was carried out to identify small drug-like compounds able to show structural and functional mimicry of the high affinity ligand X77, potent non-covalent inhibitor of SARS-COV-2 main protease (MPro). In doing so, the X77-mimetic candidates were predicted based on the crystal X77-MPro structure by a public web-oriented virtual screening platform Pharmit. Models of these candidates bound to SARS-COV-2 MPro were generated by molecular docking, quantum chemical calculations and molecular dynamics simulations. At the final point, analysis of the interaction modes of the identified compounds with MPro and prediction of their binding affinity were carried out. Calculation revealed 5 top-ranking compounds that exhibited a high affinity to the active site of SARS-CoV-2 MPro. Insights into the ligand - MPro models indicate that all identified compounds may effectively block the binding pocket of SARS-CoV-2 MPro, in line with the low values of binding free energy and dissociation constant. Mechanism of binding of these compounds to MPro is mainly provided by van der Waals interactions with the functionally important residues of the enzyme, such as His-41, Met-49, Cys-145, Met-165, and Gln-189 that play a role of the binding hot spots assisting the predicted molecules to effectively interact with the MPro active site. The data obtained show that the identified X77-mimetic candidates may serve as good scaffolds for the design of novel antiviral agents able to target the active site of SARS-CoV-2 MPro.Communicated by Ramaswamy H. Sarma.
Computation screening of narcissoside a glycosyloxyflavone for potential novel coronavirus 2019 (COVID-19) inhibitor
Biomed J 2020 Aug;43(4):363-367.PMID:32426388DOI:10.1016/j.bj.2020.05.002.
Background: The present study demonstrates the potential of flavanoid narcissoside against the novel corona virus (COVID-19) complications using molecular docking studies. Methods: The computation molecular docking screening was performed using Molegro Virtual Docker software (MVD) with grid resolution of 30 Å. Protein of COVID 19 virus was taken from protein data bank. Results: The standard inhibitor X77 (N-(4-tert-butylphenyl)-N-[(1R)-2-(cyclohexylamino)-2-oxo-1-(pyridin-3-yl)ethyl]-1H-imidazole-4-carboxamide) identified from the protein inhibitor complex 6W63 from protein data bank was docked with COVID 19 protein 6W63 which showed MolDock score of -156.913, rerank Sore -121.296 and H Bond -5.7369, while the flavanoid narcissoside had showed MolDock score -180.739, Rerank Sore -137.092 and H Bond -18.6771. The narcissoside showed potent inhibitory effect which is greater than standard X77. The result showed that narcissoside have high affinity towards 6W63 as it showed thirteen hydrogen bonds with nine amino acids (Arg 188, Glu 166, His 164, Cys 145 (2 bonds), Asn 14 (2 bonds), Cys 44 (2 bonds), His 41 (2 bonds), Gln 192, Thr 190) while X777 showed four hydrogen bonds with amino acids (Gly 143, Cys 145, Glu 166, Ser 144). Conclusion: From computation approach it was concluded that narcissoside is a potent inhibitor of viral COVID 19 protein 6W63. The narcissoside have high affinity and inhibition potential than standard inhibitor X77 (N-(4-tert-butylphenyl)-N-[(1R)-2-(cyclohexylamino)-2-oxo-1-(pyridin-3-yl)ethyl]-1H-imidazole-4-carboxamide). The narcissoside predicted as more potent inhibitor which can be further optimize, pharmacologically and clinically evaluated for the treatment of novel coronavirus COVID-19.
Repositioning of anti-dengue compounds against SARS-CoV-2 as viral polyprotein processing inhibitor
PLoS One 2022 Nov 16;17(11):e0277328.PMID:36383621DOI:10.1371/journal.pone.0277328.
A therapy for COVID-19 (Coronavirus Disease 19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains elusive due to the lack of an effective antiviral therapeutic molecule. The SARS-CoV-2 main protease (Mpro), which plays a vital role in the viral life cycle, is one of the most studied and validated drug targets. In Several prior studies, numerous possible chemical entities were proposed as potential Mpro inhibitors; however, most failed at various stages of drug discovery. Repositioning of existing antiviral compounds accelerates the discovery and development of potent therapeutic molecules. Hence, this study examines the applicability of anti-dengue compounds against the substrate binding site of Mpro for disrupting its polyprotein processing mechanism. An in-silico structure-based virtual screening approach is applied to screen 330 experimentally validated anti-dengue compounds to determine their affinity to the substrate binding site of Mpro. This study identified the top five compounds (CHEMBL1940602, CHEMBL2036486, CHEMBL3628485, CHEMBL200972, CHEMBL2036488) that showed a high affinity to Mpro with a docking score > -10.0 kcal/mol. The best-docked pose of these compounds with Mpro was subjected to 100 ns molecular dynamic (MD) simulation followed by MM/GBSA binding energy. This showed the maximum stability and comparable ΔG binding energy against the reference compound (X77 inhibitor). Overall, we repurposed the reported anti-dengue compounds against SARS-CoV-2-Mpro to impede its polyprotein processing for inhibiting SARS-CoV-2 infection.
Isolation and In Silico SARS-CoV-2 Main Protease Inhibition Potential of Jusan Coumarin, a New Dicoumarin from Artemisia glauca
Molecules 2022 Mar 31;27(7):2281.PMID:35408682DOI:10.3390/molecules27072281.
A new dicoumarin, jusan coumarin, (1), has been isolated from Artemisia glauca aerial parts. The chemical structure of jusan coumarin was estimated, by 1D, 2D NMR as well as HR-Ms spectroscopic methods, to be 7-hydroxy-6-methoxy-3-[(2-oxo-2H-chromen-6-yl)oxy]-2H-chromen-2-one. As the first time to be introduced in nature, its potential against SARS-CoV-2 has been estimated using various in silico methods. Molecular similarity and fingerprints experiments have been utilized for 1 against nine co-crystallized ligands of COVID-19 vital proteins. The results declared a great similarity between Jusan Coumarin and X77, the ligand of COVID-19 main protease (PDB ID: 6W63), Mpro. To authenticate the obtained outputs, a DFT experiment was achieved to confirm the similarity of X77 and 1. Consequently, 1 was docked against Mpro. The results clarified that 1 bonded in a correct way inside Mpro active site, with a binding energy of -18.45 kcal/mol. Furthermore, the ADMET and toxicity profiles of 1 were evaluated and showed the safety of 1 and its likeness to be a drug. Finally, to confirm the binding and understand the thermodynamic characters between 1 and Mpro, several molecular dynamics (MD) simulations studies have been administered. Additionally, the known coumarin derivative, 7-isopentenyloxycoumarin (2), has been isolated as well as β-sitosterol (3).