D77(497836-10-9)藥理學(xué)：

※D77是一種抗HIV-1抑制劑，通過(guò)作用于整合酶與細(xì)胞LEDGF / p75的相互作用，D77抑制HIV-1（IIIB）復(fù)制，作用于MT-4細(xì)胞時(shí)，EC50值23.8μg/ ml（C8166細(xì)胞時(shí)，EC50值5.03μg/ ml）

※D77是抗HIV-1抑制劑，靶向整合酶和細(xì)胞LEDGF / p75之間的相互作用。D77在MT-4細(xì)胞中的EC50值為23.8μg/ ml，抑制HIV-1（IIIB）復(fù)制（對(duì)于C8166細(xì)胞為5.03μg/ ml）。IC50值：23.8μg/ ml（在MT-4細(xì)胞中為EC50），5.03μg/ ml（在C8166細(xì)胞中為EC50）目標(biāo)：體外HIV-1：D77對(duì)HIV-1整合酶催化核心具有高度特異性的結(jié)合親和力與未處理D77的細(xì)胞相比，D77引起濃度依賴性的α-半乳糖苷酶活性急劇下降。D77揭示了對(duì)IN與IBD相互作用的顯著抑制活性.

1、Insight into the inhibitory mechanism and binding mode between D77 and HIV-1 integrase by molecular modeling methods
Ping Li 1, Jian Jun Tan, Ming Liu, Xiao Yi Zhang, Wei Zu Chen, Cun Xin Wang

Abstract 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.