Authors:IS Fernández, P Cuevas, J Angulo, P López-Navajas, A Canales-Mayordomo, R González-Corrochano, RM Lozano, S Valverde, J Jimenez-Barbero, A Romero, G Gimenez-Gallego

作者：IS Fernández, P Cuevas, J Angulo, P López-Navajas, A Canales-Mayordomo, R González-Corrochano, RM Lozano, S Valverde, J Jimenez-Barbero, A Romero, G Gimenez-Gallego

Journal:Journal of Biological Chemistry, 2010, Volume 285, Issue 15, Pages 11714-11729

期刊：《生物化学杂志》，2010年，第285卷，第15期，第11714-11729页

DOI:10.1074/jbc.M109.064618

Objective:

This study investigates gentisic acid (GA; 2,5-dihydroxybenzoic acid), a plant secondary metabolite and a catabolite of aspirin. The authors discovered that GA is a potent inhibitor of fibroblast growth factors (FGFs), proteins involved in intercellular signaling that, when improperly mobilized, contribute to disease pathology. GA and its derivatives represent a new class of fibroblast growth factor inhibitors, potentially useful in treating cancer and angiogenesis-dependent diseases.

研究目的：

本研究调查了槲皮酸（GA；2,5-二羟基苯甲酸），这种化合物是植物的次级代谢产物，也是阿司匹林的代谢产物。作者发现GA是一种强效的成纤维细胞生长因子（FGF）抑制剂。FGF是在细胞间信号传导中起关键作用的蛋白质，当其被不恰当地释放时，会导致疾病病理。GA及其衍生物代表了一类新的FGF抑制剂，可能对癌症和依赖血管生成的疾病的治疗有用。

Key Findings:

1. **Inhibition Mechanisms**: GA was shown to interfere with the assembly of signaling complexes that trigger FGF-driven mitogenesis through two different mechanisms.
2. **In Vivo Efficacy**: Evidence from disease models suggested that this new class of inhibitors could be effective in treating cancer and other diseases related to angiogenesis.
3. **Experimental Procedures**: The cDNAs encoding FGF-1 and FGF-2 were cloned and expressed in *Escherichia coli*, followed by purification through heparin-Sepharose chromatography. Various assays confirmed the inhibitory activity of GA on FGF.

主要发现：

1. **抑制机制**: GA通过两种不同的机制干扰触发FGF驱动的有丝分裂的信号复合体的组装。
2. **体内疗效**: 疾病模型的证据表明，这类新的抑制剂可能在治疗癌症和其他依赖血管生成的疾病方面有效。
3. **实验程序**: 编码FGF-1和FGF-2的cDNA被克隆并在*大肠杆菌*中表达，然后通过肝素-琼脂糖亲和层析纯化。各种检测证实了GA对FGF的抑制活性。

Related Compounds and CAS Numbers

1. **Gentisic Acid**: CAS 490-79-9
2. **Aspirin (Acetylsalicylic Acid)**: CAS 50-78-2
3. **Salicylic Acid**: CAS 69-72-7