PNAS：新计算机建模技术创造出新的抗癌药物

近日，夏威夷癌症研究中心的James Turkson博士领导的研究团队创建了一个名为BP-1-102的新型抗癌药物。该药物可以口服，其作用靶标就是针对触发许多类型癌症包括肺癌、乳腺癌、皮肤癌的关键蛋白质。

BP-1-102是研究团队基于计算机分析STAT3蛋白创造出来的，Stat 3能促进异常细胞的生长，导致癌症的发生于发展。

BP-1-102的一个独特的功能是即使口服后仍然能非常有效对抗癌症。目前，大多数抗癌药物需要静脉注射（IV），这不但需要医院或诊所特有设施，同时也增加了癌症患者的财力、物力和情感负担。

目前，乳腺癌和肺癌是最常见癌症类型，在美国每年有超过20万人因这两种癌症疾病而死亡。在夏威夷每年平均有1500例被确证患有这两种类型癌症，超过600人死于乳腺癌和肺癌。

doi:10.1073/pnas.1121606109
Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts

Xiaolei Zhanga, Peibin Yueb, Brent D. G. Pagec, Tianshu Lia, Wei Zhaoa, Andrew T. Namanjad, David Paladinob, et al.

Computer-aided lead optimization derives a unique, orally bioavailable inhibitor of the signal transducer and activator of transcription (Stat)3 Src homology 2 domain. BP-1-102 binds Stat3 with an affinity (K_D) of 504 nM, blocks Stat3–phospho-tyrosine (pTyr) peptide interactions and Stat3 activation at 4–6.8 μM, and selectively inhibits growth, survival, migration, and invasion of Stat3-dependent tumor cells. BP-1-102–mediated inhibition of aberrantly active Stat3 in tumor cells suppresses the expression of c-Myc, Cyclin D1, Bcl-xL, Survivin, VEGF, and Krüppel-like factor 8, which is identified as a Stat3 target gene that promotes Stat3-mediated breast tumor cell migration and invasion. Treatment of breast cancer cells with BP-1-102 further blocks Stat3–NF-κB cross-talk, the release of granulocyte colony-stimulating factor, soluble intercellular adhesion molecule 1, macrophage migration-inhibitory factor/glycosylation-inhibiting factor, interleukin 1 receptor antagonist, and serine protease inhibitor protein 1, and the phosphorylation of focal adhesion kinase and paxillin, while enhancing E-cadherin expression. Intravenous or oral gavage delivery of BP-1-102 furnishes micromolar or microgram levels in tumor tissues and inhibits growth of human breast and lung tumor xenografts.