D77
目录号 : GC33982
D77是一种抗HIV-1抑制剂,靶向作用于整合酶与细胞LEDGF/p75的相互作用,D77抑制HIV-1(IIIB)复制,作用于MT-4细胞时,EC50值为23.8μg/ml(C8166细胞时,EC50值为5.03μg/ml)。
Cas No.:497836-10-9
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
D77 is anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75. D77 inhibits HIV-1(IIIB) replication by EC50 value of 23.8 μg/ml in MT-4 cell (5.03 μg/ml for C8166 cells).IC50 value: 23.8 μg/ml (EC50, in MT-4 cell ), 5.03 μg/ml (EC50, in C8166 cell)Target: HIV-1in vitro: D77 exhibits a highly specific binding affinity to HIV-1 integrase catalytic core domain.D77 induces a dramatic concentration-dependent decrease of α-galactosidase activity compared to the D77-untreated cells. D77 reveals a significant inhibition activity against the interaction of IN with IBD.
[1]. Du L, et al. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75. Biochem Biophys Res Commun. 2008 Oct 10;375(1):139-144.
| Cas No. | 497836-10-9 | SDF | |
| Canonical SMILES | O=C(O)C1=CC=C(COC2=CC(Br)=C(/C=C(SC(N3CC(C4=CC=CC=C4)=O)=O)/C3=O)C=C2OCC)C=C1 | ||
| 分子式 | C28H22BrNO7S | 分子量 | 596.45 |
| 溶解度 | Soluble in DMSO | 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 | 1.6766 mL | 8.3829 mL | 16.7659 mL |
| 5 mM | 0.3353 mL | 1.6766 mL | 3.3532 mL |
| 10 mM | 0.1677 mL | 0.8383 mL | 1.6766 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。
D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75
Biochem Biophys Res Commun 2008 Oct 10;375(1):139-44.PMID:18691555DOI:10.1016/j.bbrc.2008.07.139.
Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. Since LEDGF/p75 plays an important role in HIV integration, disruption of the LEDGF/p75 interaction with IN has provided a special interest for anti-HIV agent discovery. In this work, we reported that a benzoic acid derivative, 4-[(5-bromo-4-{[2,4-dioxo-3-(2-oxo-2-phenylethyl)-1,3-thiazolidin-5-ylidene]methyl}-2-ethoxyphenoxy)methyl]benzoic acid (D77) could potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution thus exhibiting antiretroviral activity. Molecular docking with site-directed mutagenesis analysis and surface plasmon resonance (SPR) binding assays has clarified possible binding mode of D77 against HIV-1 integrase. As the firstly discovered small molecular compound targeting HIV-1 integrase interaction with LEDGF/p75, D77 might supply useful structural information for further anti-HIV agent discovery.
Insight into the inhibitory mechanism and binding mode between D77 and HIV-1 integrase by molecular modeling methods
J Biomol Struct Dyn 2011 Oct;29(2):311-23.PMID:21875151DOI:10.1080/07391102.2011.10507387.
Integrase is an essential enzyme in the life cycle of Human immunoficiency virus type 1 (HIV-1) and also an important target for designing integrase inhibitors. In this paper, the binding modes between the wild type integrase core domain (ICD) and the W131A mutant ICD with the benzoic acid derivative--D77 were investigated using the molecular docking combined with molecular dynamics (MD) simulations. The result of MD simulations showed that the W131A substitution affected the flexibility of the region 150-167 in both the monomer A and B of the mutant type ICD. In principle, D77 interacted with the residues around the Lens Epithelium-Derived Growth Factor (LEDGF/p75) binding site which is nearby the HIV-1 integrase dimer interface. However, the specific binding modes for D77-wild type integrase and D77-mutant integrase systems are various. According to the binding mode of D77 with the wild type ICD, D77 can effectively intervene with the binding of LEDGF/p75 to integrase due to a steric hindrance effect around the LEDGF/p75 binding site. In addition, we found that D77 might also affect its inhibitory action by reducing the flexibility of the region 150-167 of integrase. Through energy decomposition calculated with the Molecular Mechanics Generalized Born Surface Area approach to estimate the binding affinity, it seems likely that W131 and E170 are indispensable for the ligand binding, as characterized by the largest binding affinity. All the above results are consistent with the experimental data, providing us with some helpful information not only for the understanding of the mechanism of this kind of inhibitor but also for the rational drug design.
Intracellular drug binding affinities by NMR
Acta Crystallogr D Struct Biol 2021 Oct 1;77(Pt 10):1216-1217.PMID:34605425DOI:10.1107/S2059798321010135.
A commentary on the article by Luchinat et al. [(2021), Acta Cryst. D77, 1247–1258] where they describe an approach to identify the details of a compound binding to a molecular target using in-cell NMR to provide intracellular binding affinities.
Effects of Medicinal Plants and Organic Selenium against Ovine Haemonchosis
Animals (Basel) 2021 May 5;11(5):1319.PMID:34063070DOI:10.3390/ani11051319.
The objective of this study was to determine the effect of traditional medicinal plants typical to Central Europe as well as organic selenium on increasing the resistance of lambs to gastrointestinal nematode (GIN) infection with Haemonchus contortus. 21 female lambs were infected with third-stage larvae of H. contortus on the day (D) 0 and re-infected on D49 and D77. The animals were divided into three groups based on a treatment diet: a basal diet (control), a diet enriched with dry plants (Herbmix), and a diet enriched with selenized yeast (Selplex). The number of eggs per gram (EPG) of feces was quantified on D21, D28, D35, D42, D49, D56, D63, D70, D77, D84, D91, D98, D105, D112, and D119. The mean reductions in EPG on D28 were 43.4 and 28.6% for Selplex and Herbmix, respectively. The reduction in egg output was nearly uniform throughout the experiment for Selplex. However, for Herbmix the mean reduction was only 19.8% up to D91 and 46.1% after D91. Glutathione peroxidase activity in the blood from D35 to D98 was two to three-fold higher for Selplex than the other groups. Both supplements slowed the dynamics of GIN infection and gradually increased the resistance of lambs against ovine haemonchosis.
Detection of new allotypic variants of bovine λ-light chain constant regions in different cattle breeds
Dev Comp Immunol 2012 Jan;36(1):130-9.PMID:21741991DOI:10.1016/j.dci.2011.06.011.
In the cattle breeds German Black Pied (GBP), German Simmental (GS), Holstein Friesian (HF), Aubrac (A) three transcribed allotypic variants in isotype IGLC2 and five allotypic variants in isotype IGLC3 were identified. Substitutions within the putative interface to CH1 at position 11 and 79 were noted. In IGLC2(b), K79E led to a charge conversion. In IGLC3(b) and IGLC3(c), the E79N replacement removed the charge while the T11K substitution resulted in a positively charged amino acid residue. In addition, D15 and T16 were found in IGLC2(c), IGLC3(b), and IGLC3(c). Substitutions located on the outer site of the molecule were observed in IGLC2(b) (V40, H45.5), IGLC2(c) (A1, V40, D77), IGLC3(b) (A1, D77, D109, P127), IGLC3(c) (A1, G45.5, D77, D109, P127), IGLC3(d) (D109), and IGLC3(e) (A1). Amino acid residues P83 (IGLC2(c), IGLC3(b), IGLC3(c)), N93 (IGLC2(b)), D93 (IGLC3(b)), and G93 (IGLC3(c)) were positioned in cavities but seemed to be accessible for solvents.