VALIDATION OF HMGI-C AS A DRUG TARGET IN OBESITY

HMGene独特的、新颖的方法是开发直接作用于脂肪组织的药物。II期的目标是进一步验证hgi - c，一种调节脂肪形成基因表达的建筑转录因子，作为肥胖的药物靶点。I期研究表明，hgi - c失活可逆转瘦素缺乏引起的肥胖。第二阶段将扩展这些研究，以证明饮食引起的肥胖同样适用，这是一种更生理的模型，更接近于人类疾病。由于HMGI-C是一种转录调节因子，位于基因组级联的顶端，DNA微阵列和RNA差异显示技术将用于识别HMGI-C基因组通路中的基因，从而提供新的药物靶点。最后，由于最终目标是开发一种安全有效的治疗肥胖的方法，因此将开发生化和基于细胞的检测方法，以筛选可能用于治疗肥胖的HMGI-C的小分子抑制剂。建议的商业应用：本项目的成功完成将为发现有效的、具有临床价值的抗肥胖药物开辟新的前景，这将具有巨大的商业潜力。据估计，美国处方抗肥胖药物的年销售额约为10亿美元。对于非处方药来说，潜在市场被认为是100亿美元。

The unique, novel approach of HMGene to obesity treatment is to develop drugs that act directly on adipose tissue. The goal of Phase II will be to further validate HMGI-C, an architectural transcription factor which regulates gene expression in adipogenesis, as a drug target in obesity. In Phase I, it was shown that inactivation of HMGI-C reverses the obesity induced by leptin deficiency. Phase II will extend those studies to show that the same holds true for diet induced obesity which is a more physiological model and more closely parallels the human disease. As HMGI-C is a transcriptional regulator and sits at the apex of a genomic cascade, DNA microarray and RNA differential display technology will be used to identify genes in the HMGI-C genomic pathway which will provide novel drug targets. Finally, as the ultimate goal is to develop a safe, effective therapeutic for the treatment of obesity, both biochemical and cellular based assays will be developed in order to screen for small molecule inhibitors of HMGI-C which may be useful in the treatment of obesity. PROPOSED COMMERCIAL APPLICATIONS: Successful completion of this project would open up new prospects of the discovery of effective, clinically valuable anti-obesity drugs, which would have an enormous commercial potential. It is estimated that the U.S. mark for a prescription anti-obesity drug is approximately $ 1 billion in annual sales. For an over-the-counter drug, potential market is believed to be $10 billion.