近日,,夏威夷癌癥研究中心的James Turkson博士領(lǐng)導(dǎo)的研究團隊創(chuàng)建了一個名為BP-1-102的新型抗癌藥物。該藥物可以口服,,其作用靶標(biāo)就是針對觸發(fā)許多類型癌癥包括肺癌,、乳腺癌、皮膚癌的關(guān)鍵蛋白質(zhì),。
BP-1-102是研究團隊基于計算機分析STAT3蛋白創(chuàng)造出來的,Stat 3能促進異常細胞的生長,,導(dǎo)致癌癥的發(fā)生于發(fā)展,。
BP-1-102的一個獨特的功能是即使口服后仍然能非常有效對抗癌癥。目前,,大多數(shù)抗癌藥物需要靜脈注射(IV),,這不但需要醫(yī)院或診所特有設(shè)施,同時也增加了癌癥患者的財力、物力和情感負擔(dān),。
目前,,乳腺癌和肺癌是最常見癌癥類型,,在美國每年有超過20萬人因這兩種癌癥疾病而死亡,。在夏威夷每年平均有1500例被確證患有這兩種類型癌癥,,超過600人死于乳腺癌和肺癌,。(生物谷:Bioon.com)
doi:10.1073/pnas.1121606109
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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 (KD) 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.