在研究确定GBA-05和AKBA等乳香酸类等化合物具有抑制胰腺癌细胞系生长活性的基础上，进行深入的作用机理研究。以转染cyclin D1(T286A)的AsPC-1细胞为研究对象，考察降解cyclin D1水平与这类化合物抑制胰腺癌细胞生长的关系；研究GBA-05等化合物通过降解cyclin D1抑制胰腺癌细胞生长的具体通路；探讨抑制Pin1活性与降解cyclin D1之间的关系。开展基于Pin1结构的化合物设计，对天然乳香酸类化合物AKBA和ATA进行系统的结构修饰和改造，扩展化学结构上的多样性；进行体外抗肿瘤细胞增殖活性筛选和Pin1抑制试验，探讨结构和活性之间的关系。寻找具有特异性抑制Pin1、降解cyclin D1的抗肿瘤活性化合物，为自主创制新药奠定基础。

Boswellic acids have been shown to have antitumor activities and a series of compounds were designed and synthesized based on their active groups. GBA-05 is a modified derivative of boswellic acid with significantly improved antitumor effects in pancreatic cancer with degradation of cyclin D1, a key regulator of cell cycle progression. The requirement of cyclin D1 degradation by GBA-05 to inhibit cancer cell growth will be determined using cells transfected with mutant cyclin D1 defecting proteolysis. The signaling pathway of GBA-05-induced cyclin D1 down-regulation will be determined by testing inhibition of Pin1, a key enzyme stabilizing cyclin D1. Based on the crystal structure of the Pin1/EGCG complex, a series of new boswellic acids derivatives will be designed and synthesized utilizing AKBA and ATA as the lead compounds. Antiproliferative activities of these compounds will be determined in pancreatic, breast and prostate cancer cell lines. The quantitative structure-activity relationships (QSAR) of antiproliferative and inhibiting Pin1 activities of boswellic acid derivatives will be determined. Through these approaches we hope to develop a novel group of anticancer agents with a specific target.