1246815-54-2Relevant academic research and scientific papers
Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates
Yao, Yuqin,Yu, Lin,Su, Xiaolan,Wang, Yuxi,Li, Wenting,Wu, Yangpin,Cheng, Xiangzheng,Zhang, Hang,Wei, Xian,Chen, Hao,Zhang, Rundong,Gou, Lantu,Chen, Xiaoxin,Xie, Yongmei,Zhang, Bo,Zhang, Yonghui,Yang, Jinliang,Wei, Yuquan
, p. 5 - 17 (2015)
Antibody-drug conjugates (ADCs), combining monoclonal antibody with high cytotoxicity chemotherapeutic drug (warhead), have been successfully applied for clinical cancer therapy. Linker technology to select and design linker connecting warhead with antibo
A multi-stimuli responsive nanoparticulate SN38 prodrug for cancer chemotherapy
Liu, Xun,Huang, Qian,Yang, Caixia,Zhang, Qianzhi,Chen, Wan,Shen, Youqing,Sui, Meihua
, p. 661 - 670 (2017)
Modification of drug delivery systems (DDSs) with stimuli-responsive elements could significantly increase the tumor-specific delivery of anticancer drugs. Herein we synthesized a novel multiple stimuli-responsive SN38 prodrug, named PEG-S-S-SN38, by conjugating PEG (MW: 2000) and SN38 with disulfide bonds and carbonic ester linkages as linkers for efficient delivery of SN38. The amphiphilic PEG-S-S-SN38, with a high SN38 loading content, could self-assemble into nanoparticles (NPs) with a stable diameter of ～73 nm. PEG-S-S-SN38 NPs release SN38 very slowly at physiological pH, while they quickly release SN38 in the presence of GSH, esterase and H2O2, all of which are abundant in the cytoplasm of cancer cells. PEG-S-S-SN38 NPs could be quickly internalized into tumor cells, achieve vesicular escape and nuclear localization, and exhibit remarkable in vitro anticancer activity similar to SN38. Encouragingly, PEG-S-S-SN38 NPs exhibit the same effects on cell cycle regulations as SN38 in vitro. Most importantly, the inhibition rate of tumor growth induced by PEG-S-S-SN38 NPs in a xenograft tumor model reached 72.49% ± 6.26%, which was nearly double that of the corresponding clinical drug CPT-11 (38.64% ± 13.04%) at a dosage equivalent to 10 mg kg?1 SN38. Our data suggest that the multi-stimuli responsiveness of PEG-S-S-SN38 NPs remarkably enhances their therapeutic activity against heterogeneous or mixed cell population in tumors, making this new DDS a promising alternative to CPT-11 for cancer treatment.
IRINOTECAN IMMUNOASSAY
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Page/Page column 26; 29, (2011/06/26)
Novel conjugates of the pharmaceutically active metabolite of irinotecan and novel immunogens derived from this pharmaceutically active metabolite and monoclonal antibodies generated by these immunogens which are useful in immunoassays for the quantificat
Camptothecin intermediates and prodrugs and methods of preparation thereof
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Page/Page column 11, (2008/06/13)
The present invention relates to novel intermediates and prodrugs of camptothecin and related analogs.
A versatile prodrug approach for liposomal core-loading of water-insoluble camptothecin anticancer drugs
Liu, Xinli,Lynn, Bert C.,Zhang, Junhong,Song, Lin,Bom, David,Du, Wu,Curran, Dennis P.,Burke, Thomas G.
, p. 7650 - 7651 (2007/10/03)
We describe a versatile prodrug strategy for loading the liposomal lumen with water-insoluble camptothecins. The procedure involves conversion of an active camptothecin analogue to a 20-OR ω-aminoalkanoanic ester prodrug in which R = CO[CH2]nNH2 and n = 1-3. The basic amino group of the prodrug serves three roles. First, at pH ranges of 3-5, the amine enhances aqueous solubility. Second, it enhances responsiveness to a transmembrane ammonium sulfate gradient across the liposomal bilayer, thereby facilitating active loading of the agent into the liposomal aqueous core. Third, at a physiological pH of 7 or above (the pH to be encountered following drug release at the tumor site), the nucleophilicity of the amine manifests itself and cyclization to the C-21 carbonyl carbon occurs. This cyclization triggers a rapid and convenient nonenzymatic decomposition process that releases active camptothecin. Accordingly, this novel liposomal approach offers a potential system for tumor-targeting prodrugs of many water-insoluble camptothecins, including the highly lipophilic and clinically attractive analogues SN-38, 9-nitrocamptothecin and DB-67. The rate of formation of the active agent at the tumor site can be controlled through the selection of n (the length of the alkyl spacer group). Copyright
