CAS: 168682-53-9; Ethyl N5-((R)-3-(Benzylthio)-1-(((R)-2-Ethoxy-2-Oxo-1-Phenylethyl)Amino)-1-Oxopropan-2-yl)-L-Glutaminate

上下游产品

(S)-4-{(R)-2-Benzylsulfanyl-1-[((R)-Ethoxycarbonyl-Phenyl-Methyl)-Carbamoyl]-Ethylcarbamoyl}-2-Tert-Butoxycarbonylamino-Butyric Acid Ethyl Ester
Boc-Cys(Bzl)-D-Phg-Oet 247233-37-0

📜左旋苯甘氨酸置于n-甲基吗啉,盐酸,氯化亚砜,1-羟基苯并三唑,盐酸-N-乙基-N'-(3-二甲氨基丙基)碳二亚胺体系中,用 1,4-二氧六环,N,N-二甲基甲酰胺 用作溶剂,化学反应 1.33H,反应生成Ezatiostat游离的
参考文献:Reversal Of Multiple Drug Resistance In Cholangiocarcinoma By The Glutathiones-Transferase-π-Specific Inhibitoro1-Hexadecyl-γ-Glutamyl-S-Benzylcysteinyl-D-Phenylglycine Ethylester
标题:Reversal Of Multiple Drug Resistance In Cholangiocarcinoma By The Glutathiones-Transferase-π-Specific Inhibitoro1-Hexadecyl-γ-Glutamyl-S-Benzylcysteinyl-D-Phenylglycine Ethylester
摘要:胆管癌对化疗有明显的耐药性,预后不良,但其耐药机制尚不清楚.本研究探讨了谷胱甘肽 S-转移酶-π(gstp1-1)是否参与了胆管癌对抗癌药物的耐药性,以及 Gstp1-1 特异性抑制剂能否克服这种耐药性.首先,免疫组化检查显示,17 例胆管癌标本中的 Gstp1-1 均呈强染色,与组织学类型无关.将gstp1-1反义表达载体转染到人胆管癌细胞系(hucct1)后,细胞内的gstp1-1浓度明显降低,与模拟转染者相比,转染者对阿霉素(adr),顺铂以及美法仑和4-羟基过氧环磷酰胺(4-Hc)等烷化剂的敏感性明显增加.接下来,我们通过延长γ-谷氨酰-S-苄基半胱氨酰-苯基甘氨酰二乙基酯 N 端乙酯的碳链,合成了 Gstp1-1 特异性抑制剂,并对其进行了药代动力学研究.在测试的六种 Gstp1-1 抑制剂中,O 1-十六烷基-γ-谷氨酰-S-苄基半胱氨酰-二苯甘氨酸乙酯(c16C2)的中心区容积和稳态分布容积最小,清除率次之,是体内最有效的抑制剂.用 C16C2 处理 Hucct1 细胞时,Adr 或 4-Hc 的 Ic50 值会随着 Gstp1-1 活性的降低而降低,其降低程度与 Gstp1-1 活性的降低程度呈剂量依赖关系.在异种移植模型中,与 C16C2 联合治疗可明显增强 Adr 或环磷酰胺的抗肿瘤活性.总之,我们的研究结果表明,Gstp1-1 是胆管癌抗癌药物的耐药因子,而 C16C2 作为一种 Gstp1-1 特异性抑制剂,是一种有效的抗耐药药物.
Doi:10.1124/jpet.103.052696

专利信息

专利号:US-11285169-B2
优先权日:2013-03-13
标题 :Methods for modulating chemotherapeutic cytotoxicity
发明人：ROBERTS DAVID D; SOTO PANTOJA DAVID R
权利人:US HEALTH
摘要:Methods of reducing cytotoxicity of a chemotherapeutic agent to non-cancer cells by administering to a subject with cancer an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent, such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are provided. Example disclosed methods reduce cardiotoxicity. In one example, the methods include administering to a subject with cancer an effective amount of a CD47 antisense morpholino oligonucleotide and an anthracycline such as doxorubicin. Methods of increasing cytotoxicity of a chemotherapeutic agent in cancer cells by administering to a subject with a tumor an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are also provided. In some embodiments, the inhibitor of CD47 signaling is administered to the subject before, during, or after the administration of the DNA damaging agent.