Hydrophilically enhanced 3-carboranyl thymidine analogues (3CTAs) for boron neutron capture therapy (BNCT) of cancer.
Hydrophilically enhanced 3-carboranyl thymidine analogues (3CTAs) for boron neutron capture therapy (BNCT) of cancer.
复制标题
亲水性增强的 3-碳硼烷基胸苷类似物 (3CTA)，用于癌症的硼中子捕获疗法 (BNCT)。
DOI：
10.1016/j.bmc.2006.06.039
复制
发表时间：
2006
影响因子：
3.5
通讯作者：
W. Tjarks
中科院分区：
文献类型：
--
作者：
Sureshbabu Narayanasamy;B. Thirumamagal;Jayaseharan Johnsamuel;Youngjoo Byun;A. S. Al;E. Usova;Guirec Y. Cosquer;Junhua Yan;A. Bandyopadhyaya;R. Tiwari;S. Eriksson;W. Tjarks
设计合成了5种新型3-碳硼基胸苷类似物（3cta），用于硼中子俘获治疗癌症。重组人胸腺嘧啶激酶（hTK1）以三磷酸腺苷（ATP）为磷酸供体催化了所有5种3cta的磷酸化。相对于胸苷的磷酸化率为4% ~ 64.5%。与hTK1结合性能最好的化合物相对于胸腺嘧啶的kcat/ km值为57.4%，hTK1抑制胸腺嘧啶磷酸化的ic50为92μM。在合成的5种3cta中，该药剂的理化性质总体上也是最有利的。因此，它有可能在临床前研究中取代N5-2OH，即目前的3CTA先导药物。开发了该化合物与hTK1结合的硅模型。
Five novel 3-carboranyl thymidine analogues (3CTAs) were designed and synthesized for boron neutron capture therapy (BNCT) of cancer. Phosphorylation of all five 3CTAs was catalyzed by recombinant human thymidine kinase (hTK1) using adenosine triphosphate (ATP) as the phosphate donor. The obtained phosphorylation rates ranged from 4% to 64.5% relative to that of thymidine. The compound with the most favorable hTK1 binding properties had a kcat/KMvalue of 57.4% relative to that of thymidine and an IC50of inhibition of thymidine phosphorylation by hTK1 of 92μM. Among the five synthesized 3CTAs, this agent had also the overall most favorable physicochemical properties. Therefore, it may have the potential to replace N5–2OH, the current lead 3CTA, in preclinical studies. An in silico model for the binding of this compound to hTK1 was developed.
影响因子：
7.3
作者：
McGovern, SL;Shoichet, BK
通讯作者：
Shoichet, BK
影响因子：
3.1
作者：
Schwartz, JL;Tamura, Y;Krohn, KA
通讯作者：
Krohn, KA