НЮ Децян (US),ПЕТТЕР Рассел С. (US),СИНГХ Джасвиндер (US),КЛЮГ Артур Ф. (US),МАЗДИЯСНИ Хормоз (US),ЧЖУ Чжэньдон (US),ЦЯО Лисинь (US),КУНТЦ Кевин (US)
申请号：
RU2012110024/04
公开号：
RU2012110024A
申请日:
2010.09.09
申请国别(地区):
RU
年份:
2013
代理人:
摘要：
1. A conjugate containing one or more PI3 kinases containing a cysteine residue, CysX, wherein said CysX is covalently and irreversibly linked to an inhibitor, thereby maintaining inhibition of PI3 kinase, where CysX is selected from Cys862 to PI3K alpha, Cys2243 to MTOR, Cys83838 in PI3K alpha, Cys869 in PI3K gamma, Cys815 in PI3K delta, Cys841 in PI3K beta, class 1A, Cys1119 in PI3K beta, class 2, Cys3683 in DNA-PK, Cys2770 in ATM kinase, Cys2753 in ATM kinase, Cys1840 in PI4KA, Cys1844 in PI4KA or Cys1797 in PI4KA.2. The conjugate according to claim 1, containing one or more PI3 kinases containing a cysteine residue selected from: (a) Cys862 in PI3K alpha； or (b) any of Cys869 in PI3K gamma, Cys838 in PI3K alpha, Cys815 in PI3K delta, Cys841 in PI3K beta, class 1, or Cys1119 in PI3K beta, class 2.3. The conjugate according to claim 1, wherein said conjugate has the formula C: CysX modifier — inhibitory fragment Where: CysX is selected from Cys862 in PI3K alpha, Cys2243 in MTOR, Cys838 in PI3K alpha, Cys869 in PI3K-gamma, Cys815 in PI3K- delta, Cys841 in PI3K beta, class 1A, Cys1119 in PI3K beta, class 2, Cys3683 in DNA-PK, Cys2770 in ATM kinase, Cys2753 in ATM kinase, Cys1840 in PI4KA, Cys1844 in PI4KA or Cys1797 in PI4KA； the modifier is a divalent group formed by covalent binding of the active group to CysX in PI3 kinase； the active group is a functional group capable of covalently binding to CysX； the inhibitory fragment is a fragment that binds to the active site of PI3.4 kinase. The conjugate according to claim 1, wherein said conjugate has the formula C-1: Cys862-modifier is an inhibitor fragment of C-1, where: Cys862 is Cys862 in PI3 kinase； the modifier is a divalent group formed by covalent binding of the active group to Cys862 in PI3 kinase； the active group is a functional group capable of forging1. Конъюгат, содержащий одну или более PI3-киназ, содержащих остаток цистеина, CysX, причем указанный CysX ковалентно и необратимо связан с ингибитором, что о
