CAS: 478183-57-2; (R)-2-((Tert-Butoxycarbonyl)Amino)-3-(3-Chloro-4-Hydroxyphenyl)Propanoic Acid

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CAS号24424-99-5 二碳酸二叔丁酯 | CAS号162599-96-4 3-Cl-D-Tyr-OH | CAS号556-02-5 D-酪氨酸

📜D-酪氨酸置于氯化亚砜,溶剂黄146,三乙胺体系中,用 1,4-二氧六环,水 作为反应溶剂,化学反应 8.25H,反应生成 Boc-D-3-氯酪氨酸
参考文献:Cryptophycin-55/52 Based Antibody-Drug Conjugates: Synthesis,Efficacy,And Mode Of Action Studies
标题:Cryptophycin-55/52 Based Antibody-Drug Conjugates: Synthesis,Efficacy,And Mode Of Action Studies
摘要:Cryptophycin-52 (Cr52),A Tubulin Inhibitor,Exhibits Promising Antitumor Activity In Vitro (Picomolar Level) And In Mouse Xenograft Models. However,The Narrow Therapeutic Window In Clinical Trials Limits Its Further Development. Antibody-Drug Conjugate (Adc),Formed By Coupling Cytotoxic Compound (Payload) To An Antibody Via A Linker,Can Deliver Drug To Tumor Locations In A Targeted Manner By Antibody,Enhancing The Therapeutic Effects And Reducing Toxic And Side Effects. In This Study,We Aim To Explore The Possibility Of Cr52-Based Adc For Tumor Targeted Therapy. Due To The Lack Of A Coupling Site In Cr52,Its Prodrug Cryptophycin-55 (Cr55) Containing A Free Hydroxyl Was Synthesized And Conjugated To The Model Antibody Trastuzumab (Anti-Her2 Antibody Drug Approved By Fda For Breast Cancer Therapy) Via The Linkers Based On Mc-Nhs And Mc-Val-Cit-Pab-Pnp. The Average Drug-To-Antibody Ratios (Dars) Of Trastuzumab-Cr55 Conjugates (Named T-L1-Cr55,T-L2-Cr55,And T-L3-Cr55) Were 3.50,3.29,And 3.35,Respectively. These Conjugates Exhibited Potent Cytotoxicity In Her2-Positive Tumor Cell Lines With Ic50 Values At Low Nanomolar Levels (0.58-1.19 Nm). Further,They Displayed Significant Antitumor Activities At The Doses Of 10 Mg/kg In Established Ovarian Cancer (Skov3) And Gastric Cancer (Nci-N87) Xenograft Models Without Overt Toxicities. Finally,The Drug Releases Were Analyzed And The Results Indicated That T-L3-Cr55 Was Able To Effectively Release Cr55 And Further Epoxidized To Cr52,Which May Be Responsible For Its Best Performance In Antitumor Activities. In Conclusion,Our Results Demonstrated That These Conjugates Have The Potential For Tumor Targeted Therapy,Which Provides Insights To Further Research The Cr55/cr52-Based Adc For Tumor Therapy. (C) 2020 Elsevier Masson Sas. All Rights Reserved.
DOI:10.1016/j.Ejmech.2020.112364

专利信息

专利号:EP-0830136-B1
优先权日:1995-03-07
标 题:New cryptophycins from synthesis
发明人：MOORE RICHARD E; TIUS MARCUS A; BARROW RUSSELL A; LIANG JIAN; CORBETT THOMAS H; VALERIOTE FREDERICK A; HEMSCHEIDT THOMAS K; GOLAKOTI TRIMURTULU
权利人:UNIV HAWAII; UNIV WAYNE STATE
摘要:Novel cryptophycin compounds are disclosed, together with methods of producing cryptophycins by total synthesis and methods for the use of such cryptophycins in pharmaceuticals to inhibit the proliferation of mammalian cells and to treat neoplasia.

专利号:US-6013626-A
优先权日:1993-12-21
标题 :Cryptophycins from synthesis
发明人：MOORE RICHARD E; TIUS MARCUS A; BARROW RUSSELL A; LIANG JIAN; CORBETT THOMAS H; VALERIOTE FREDERICK A; GOLAKOTI TRIMURTULU; HEMSCHEIDT THOMAS K
权利人:UNIV HAWAII; UNIV WAYNE STATE
摘要:A cryptophycin compound is provided having the structure: ##STR1## Further provided are methods of producing cryptophycins by total synthesis and methods of using cryptophycins in pharmaceuticals. It is a further object of this invention to use cryptophycins to inhibit the proliferation of mammalian cells. Moreover, methods of using cryptophycins to treat neoplasia is also provided.