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¹ØÓÚJAK¼¤Ã¸¼°JAK-STATÐźÅͨ·

JAK¼Ò×å

Janus Kinase(JAK)ÊÇÒ»Àà°ûÄÚ·ÇÊÜÌåÀÒ°±Ëἤø£¬JAK¼Ò×åÓÐ4¸ö³ÉÔ±£º £ºJAK1¡¢JAK2¡¢JAK3ºÍTYK2¡£JAK1¡¢JAK2ºÍTYK2ÆÕ±é±£´æÓÚÈËÌ壬¶øJAK3Ö÷Òª±£´æÓÚ¹ÇËèϸ°û¡¢ÐØÏÙϸ°ûºÍÃâÒßϸ°ûÖС£

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ͼ1. JAK¼¤Ã¸¼ò½é

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JAK¼¤Ã¸ÓëÐźÅתµ¼¼°×ªÂ¼¼¤»îÂѰ×(Singal transducers and activators of transcription, STAT)Ö®¼äµÄÏ໥×÷ÓÃÔÚϸ°ûÒò×Ó¡¢¼¤Ëؼ°Ç÷»¯Òò×ÓµÈÊÜÌåÐźÅͨ·ÖÐʩչ×ÅÖ÷Òª×÷Óã¬Èç°×½éËØ¡¢×ÌÈÅËØºÍ¼¯Âä´Ì¼¤Òò×ӵȡ£Òò´Ë£¬JAK-STATÐźÅͨ·¹¦Ð§ÆÕ±é£¬¼ÓÈëϸ°ûµÄÔöÖ³¡¢·Ö»¯ÒÔ¼°ÃâÒßµ÷ÀíµÈÖî¶àÖ÷ÒªµÄÉúÎïѧÀú³Ì£¨Í¼2£©£¬µ«JAK¼¤Ã¸Ì«¹ý»î»¯»áµ¼ÖÂÑ×Ö¢µÈ¼²²¡µÄ±¬·¢¡£

 
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ͼ2. JAK-STATͨ·¼ÓÈëµÄϸ°ûÖÖÖÖÉúÎïѧÀú³Ì(ͼƬȪԴ£º £º²Î¿¼×ÊÁÏ[2])

 

 

JAKÒÖÖÆ¼ÁÑз¢Ç÷ÊÆ

×÷ΪҩÎï°Ðµã¿ª·¢ÒÔÀ´£¬JAKÒѾ­×ß¹ýÁ˽ü30ÄêµÄ·çÓêÀú³Ì£¬³ÉΪÑ×Ö¢¡¢×ÔÉíÃâÒß²¡¡¢°©Ö¢µÈÁìÓòµÄÈÈÃŰе㣬Èçͼ3Ëùʾ¡£JAKÒÖÖÆ¼Á³ýÁËÔÚÀà·çʪÊàŦÑ×ÖÐÁÆÐ§Í»³öÍ⣬ÉÐÓжàÖÖ˳Ӧ֢±»Åú»ò´¦ÓÚÁÙ´²Ñо¿½×¶Î£¬°üÀ¨£º £º¹ÇËèÔöÉúÐÔÖ×Áö¡¢ÒÆÖ²ÎËÞÖ÷²¡¡¢ÒøÐ¼²¡ÊàŦÑס¢Ñ×Ö¢ÐÔ³¦²¡¡¢ºì°ßÀÇ´¯ºÍǿֱ¼¹ÖùÑ׵ȡ£

 

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ͼ3. JAK²î±ðÑÇÐÍÂþÑܼ°ÏìÓ¦ÒÖÖÆ¼Á

(ͼƬȪԴ£º £º²Î¿¼×ÊÁÏ[1])

 

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PARTIAL DATA

1¡¢Ba/F3-TEL-JAK1ϸ°ûÔöֳʵÑéÊý¾Ý

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2¡¢Ba/F3-EPOR-JAK2-V617Fϸ°ûÔöÖ³¼°ÌåÄÚҩЧʵÑéÊý¾Ý

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3¡¢Ba/F3-FL-TYK2£¨È«³¤ÐòÁУ©ÊÔÑéÊý¾Ý±ÈÕÕ

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×óͼ£º £ºBMS½ÒÏþÎÄÕÂÖÐʹÓÃHTRF ¼ì²âBMS-986165ºÍTYK2-JH2µÄÁ¬ÏµÄÜÁ¦;

ÓÒͼ£º £ºÊ¹ÓÃ2121·Ç·²¹¹½¨µÄBa/F3-FL-TYK2(JH1 JH2)ϸ°û¿ÉÒÔÖ±½Ó¼ì²âBMS-986165µÈ±ä¹¹¼Á¶Ôϸ°ûÔöÖ³µÄÒÖÖÆ»îÐÔ¡£

 

×ÊÁϲο¼£º £º

[1]SCHWARTZ D M, KANNO Y, VILLARINO A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases [J]. Nature Reviews Drug Discovery, 2017, 16(12): 843-62.

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