Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA.
Fox Chase Therapeutics Discovery, Inc., USA.
Antiviral Res. 2024 Jun;226:105899. doi: 10.1016/j.antiviral.2024.105899. Epub 2024 May 3.
We recently developed compound FC-7269 for targeting the Molluscum contagiosum virus processivity factor (mD4) and demonstrated its ability to inhibit viral processive DNA synthesis in vitro and cellular infection of an mD4-dependent virus (Antiviral Res 211, 2023,105520). However, despite a thorough medicinal chemistry campaign we were unable to generate a potent second analog as a requisite for drug development. We overcame this impasse, by conjugating a short hydrophobic trivaline peptide to FC-7269 to produce FC-TriVal-7269 which significantly increased antiviral potency and reduced cellular toxicity.
我们最近开发了一种名为 FC-7269 的化合物，用于靶向传染性软疣病毒（MCV）的延伸因子（mD4），并证明其在体外抑制病毒延伸性 DNA 合成和 mD4 依赖性病毒的细胞感染的能力（Antiviral Res 211, 2023, 105520）。然而，尽管进行了彻底的药物化学研究，但我们仍无法生成一种有效的第二类似物，这是药物开发的必要条件。我们通过将一个短的疏水性三肽连接到 FC-7269 上来克服这一困境，生成了 FC-TriVal-7269，这显著提高了抗病毒活性并降低了细胞毒性。
