JP2011511076A5 - - Google Patents

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Publication number
JP2011511076A5
JP2011511076A5 JP2010545895A JP2010545895A JP2011511076A5 JP 2011511076 A5 JP2011511076 A5 JP 2011511076A5 JP 2010545895 A JP2010545895 A JP 2010545895A JP 2010545895 A JP2010545895 A JP 2010545895A JP 2011511076 A5 JP2011511076 A5 JP 2011511076A5
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JP
Japan
Prior art keywords
use according
peptidomimetic macrocycle
amino acid
polypeptide
linking agent
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JP2010545895A
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English (en)
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JP2011511076A (ja
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Priority claimed from PCT/US2009/000837 external-priority patent/WO2009099677A2/en
Publication of JP2011511076A publication Critical patent/JP2011511076A/ja
Publication of JP2011511076A5 publication Critical patent/JP2011511076A5/ja
Pending legal-status Critical Current

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Claims (27)

  1. 障害の治療を必要とするヒト患者における障害を治療するための医薬の製造におけるペプチド模倣大環状分子の使用であって、
    a)ポリペプチドの2つのアミノ酸残基の間に架橋剤を導入することによって治療用ペプチド模倣大環状分子を調製する工程、
    b)インビボアッセイにおいて最小の抗体応答についてペプチド模倣大環状分子を試験する工程、および
    c)対応する非架橋ポリペプチドと比較して前記ペプチド模倣大環状分子が減少した免疫原性の応答を有する場合に、ペプチド模倣大環状分子を医薬の製造において使用する工程
    を含む使用。
  2. 前記減少した免疫原性の応答が、インビボアッセイにおいて最小の抗体応答として証明される、請求項1に記載の使用。
  3. ペプチド模倣大環状分子がヘリックスを含む、請求項1に記載の使用。
  4. ペプチド模倣大環状分子がα−ヘリックスを含む、請求項1に記載の使用。
  5. 障害が癌である、請求項1に記載の使用。
  6. 障害が代謝障害である、請求項1に記載の使用。
  7. ペプチド模倣大環状分子がBH3ドメインを含む、請求項1に記載の使用。
  8. 前記ペプチド模倣大環状分子におけるα−炭素原子が、式R−の独立した置換基でさらに置換され、R−は、非置換もしくハロ−で置換された、アルキル、アルケニル、アルキニル、アリールアルキル、シクロアルキルアルキル、ヘテロアルキル、またはヘテロシクロアルキルである、請求項1に記載の使用。
  9. 架橋剤が接続するα−炭素原子が、式R−の置換基でさらに置換され、R−は、非置換もしくはハロ−で置換された、アルキル、アルケニル、アルキニル、アリールアルキル、シクロアルキルアルキル、ヘテロアルキル、またはヘテロシクロアルキルである、請求項8に記載の使用。
  10. 架橋剤が接続する2つのα−炭素原子が、式R−の独立した置換基でさらに置換され、R−は、非置換もしくはハロ−で置換された、アルキル、アルケニル、アルキニル、アリールアルキル、シクロアルキルアルキル、ヘテロアルキル、またはヘテロシクロアルキルである、請求項9に記載の使用。
  11. R−がアルキルである、請求項8に記載の使用。
  12. 架橋剤が2つのα−炭素原子を連結する、請求項1に記載の使用。
  13. 架橋剤が連続した炭素−炭素結合から形成される、請求項1に記載の使用。
  14. 架橋剤が連続した約9個の結合を含有する、請求項1に記載の使用。
  15. 架橋剤が連続した約12個の結合を含有する、請求項1に記載の使用。
  16. 架橋剤が少なくとも約6個の炭素原子を含む、請求項1に記載の使用。
  17. 架橋剤が少なくとも約9個の炭素原子を含む、請求項1に記載の使用。
  18. ペプチド模倣大環状分子が細胞透過性である、請求項1に記載の使用。
  19. 架橋剤の長さが、α−ヘリックスのターン当たり約5Å〜約9Åである、請求項4に記載の使用。
  20. ペプチド模倣大環状分子がBIDポリペプチドである、請求項1に記載の使用。
  21. BIDポリペプチドが、配列DIIRNIARHLAVGDNleDRSI(配列番号2)と約60%超同一であり、はテザーアミノ酸であり、Nleはノルロイシンである、請求項20に記載の使用。
  22. BIDポリペプチドが、配列DIIRNIARHLAVGDNleDRSI(配列番号2)と約80%超同一であり、はテザーアミノ酸であり、Nleはノルロイシンである、請求項20に記載の使用。
  23. BIDポリペプチドが、配列DIIRNIARHLAVGDNleDRSI(配列番号2)と約95%超同一であり、はテザーアミノ酸であり、Nleはノルロイシンである、請求項20に記載の方法。
  24. ペプチド模倣大環状分子がBIMポリペプチドである、請求項1に記載の使用。
  25. BIMポリペプチドが、アミノ酸配列IWIAQELRIGDFNAYYARR(配列番号1)と約60%超同一であり、はテザーアミノ酸である、請求項24に記載の使用。
  26. BIMポリペプチドが、アミノ酸配列IWIAQELRIGDFNAYYARR(配列番号1)と約80%超同一であり、は、テザーアミノ酸である、請求項24に記載の使用。
  27. BIMポリペプチドが、アミノ酸配列IWIAQELRIGDFNAYYARR(配列番号1)と約95%超同一であり、はテザーアミノ酸である、請求項24に記載の使用。
JP2010545895A 2008-02-08 2009-02-09 治療用ペプチド模倣大環状分子 Pending JP2011511076A (ja)

Applications Claiming Priority (3)

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US2732608P 2008-02-08 2008-02-08
US12038008P 2008-12-05 2008-12-05
PCT/US2009/000837 WO2009099677A2 (en) 2008-02-08 2009-02-09 Therapeutic peptidomimetic macrocycles

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JP2011511076A5 true JP2011511076A5 (ja) 2012-03-29

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US (4) US20090275519A1 (ja)
EP (2) EP2926827A3 (ja)
JP (2) JP2011511076A (ja)
KR (1) KR20100126361A (ja)
CN (2) CN101980718A (ja)
BR (1) BRPI0907754A2 (ja)
CA (1) CA2714251C (ja)
DE (1) DE112009000300T5 (ja)
GB (1) GB2471588A (ja)
IL (2) IL207421A0 (ja)
WO (1) WO2009099677A2 (ja)
ZA (1) ZA201005741B (ja)

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