×ðÁú¿­Ê±

EN
EN
  • ÓªÒµ×Éѯ

    Öйú£º

    Email: marketing@medicilon.com.cn

    ÓªÒµ×ÉѯרÏߣº400-780-8018

    £¨½öÏÞ·þÎñ×Éѯ£¬ÆäËûÊÂÒËÇ벦´ò´¨É³×ܲ¿µç»°£©

    ´¨É³×ܲ¿µç»°: +86 (21) 5859-1500

    ÍâÑó£º

    +1(781)535-1428(U.S.)

    0044 7790 816 954 (Europe)

    Email:marketing@medicilon.com

ÔÚÏßÁôÑÔ¡Á
µã»÷Çл»
News information
ÐÂÎÅ×ÊѶ

Ò»ÎĶÁ¶®£ºÂÑ°×½µ½â°ÐÏòǶºÏÌå (PROTAC£©

2024-11-29
|
»á¼ûÁ¿£º

Ç° ÑÔ

¹Å°åС·Ö×ÓÒ©ÎïµÄ·¢Ã÷Ö÷Òª¼¯ÖÐÔÚÖ±½ÓÓ°ÏìÂÑ°×¹¦Ð§µÄÍŽáλµã»òÕ߱乹λµãÉÏ£¬È»¶ø£¬ÕâÖÖÒªÁìͨ³£ÎÞ·¨°ÐÏòÄÇЩȱ·¦»îÐÔλµãµÄÂÑ°×£¬»ò»îÐÔλµãÊÇ¿í¶ødzµÄÍŽá¿Ú´ü¶øÄÑÒÔ±»Ð¡·Ö×ÓÍŽá¡£Òò´Ë£¬ÕâÀàÄÑÒÔ±»¹Å°åС·Ö×Ó°ÐÏòµÄÂÑ°×ͨ³£±»³ÆΪ¡°²»¿É³ÉÒ©¡±°Ðµã¡£ÈËÀàÂÑ°×ÖÊ×é°üÀ¨Ô¼Äª20000ÖÖÂÑ°×£¬µ«Ö»Óв»µ½ 1000ÖÖÂÑ°×±»Ñé֤ΪҩÎï°Ðµã£¬¾ÝÔ¤¼Æ£¬ÓÉÓÚȱ·¦Ã÷È·µÄÅäÌåÍŽá¿Ú´ü£¬Ô¼80%µÄ¼²²¡Ïà¹ØÂÑ°×ÎÞ·¨Í¨¹ý¹Å°åÒ©Îï¾ÙÐÐÓÐÓøÉÔ¤¡£

ÂÑ°×½µ½â°ÐÏòǶºÏÌå (Proteolysis Targeting Chimera, PROTAC)£¬ÊÇÒ»ÖÖÐÂÐ˵ÄÖÎÁÆ·½·¨£¬ËüʹÓÃϸ°ûµÄ×ÔÈ»ÂÑ°×Öʽµ½â»úÖÆ£¬¼´·ºËØ-ÂÑ°×øϵһÇÐ (UPS) £¬Ñ¡ÔñÐԵذÐÏò½µ½â¼²²¡·¢²¡»úÖÆÖеÄÏà¹ØÂÑ°×£¬´Ó¶ø¿ÉÄܵ÷Àí¹Å°åС·Ö×ÓÄÑÒÔ°ÐÏòµÄ¡°²»¿É³ÉÒ©¡±°Ðµã¡£Òò´Ë£¬PROTAC·Ö×ӵĿ´·¨×Ô2001ÄêÊ״ᨵÀÒÔÀ´£¬Êܵ½ÁËѧÊõ½çºÍ¹¤Òµ½çµÄÆÕ±é¹Ø×¢£¬¾­ÓÉPROTACÉè¼ÆµÄ¶à´ÎÁ¢ÒìºÍÁÙ´²Ç°Ä£×ÓµÄÑÏ¿áÆÀ¹À£¬Ê×ÅúPROTAC·Ö×ÓARV-110¡¢ARV-471ÓÚ2019Äê½øÈëÁÙ´²Ñо¿¡£ÏÖÔÚ£¬È«Çò¹²Óнü40¸öPROTAC·Ö×ÓÒÑÅú×¼ÁÙ´²ÊÔÑ飬Éæ¼°Ö×ÁöºÍ×ÔÉíÃâÒß¼²²¡µÈ˳Ӧ֢¡£ÆäÖУ¬×îÇ°ÑصÄPROTAC·Ö×ÓARV-471ÓÚ2022Äêµ×Æô¶¯ÁËÁÙ´²IIIÆÚÊÔÑé¡£

PROTACµÄ×÷ÓûúÖÆÓëÓÅÊÆ

PROTACÊÇÓÉÁ½¸öͨ¹ýÅþÁ¬×Ó (Linker) ÅþÁ¬µÄÅäÌå×é³ÉµÄÒìË«¹¦Ð§Ð¡·Ö×Ó½µ½â¼Á£ºÒ»¸öÅäÌåÕÐļ²¢ÍŽáÄ¿µÄÂÑ°× (POI) £¬¶øÁíÒ»¸öÅäÌåÕÐļ²¢ÍŽáE3·ºËØÅþÁ¬Ã¸¡£PROTACͬʱÍŽáPOIºÍÅþÁ¬Ã¸£¬Í¨¹ýÐγÉE3-½µ½â¼Á-POIÈýÔª¸´ºÏÎïÓÕµ¼POIµÄ¶à·ºËØ»¯£¬²¢Ëæºó±»26SÂÑ°×øÌå½µ½â£¬Ö®ºóPROTAC·Ö×Ó½«±»½ÓÄÉʹÓã¬ÒÔ°ÐÏòPOIµÄÁíÒ»¸ö¸±±¾¡£

·ºËØ-ÂÑ°×øϵһÇÐ.webp

·ºËØ-ÂÑ°×øϵһÇÐ[1]

PROTAC½éµ¼µÄÄ¿µÄÂÑ°×½µ½â»úÖÆ.webp

PROTAC½éµ¼µÄÄ¿µÄÂÑ°×½µ½â»úÖÆ[1]

Óë¹Å°åµÄС·Ö×ÓÒ©ÎïÏà±È£¬PROTACÓм¸¸öDZÔÚµÄÓÅÊÆ£¬°üÀ¨£º

1) ¹Å°åС·Ö×ÓÒ©ÎïµÄÑо¿Í¨³£¼¯ÖÐÔÚ¿ª·¢¸ßÇ׺ÍÁ¦ÒÖÖƼÁÉÏ£¬ÕâЩÒÖÖƼÁͨ³£°ÐÏòÂѰ׵ĻîÐÔλµã£¬»òÕß°ÐÏòÂѰ׵ı乹λµã£¬ÒԹرÕPOIµÄ¹¦Ð§£¨¡°Õ¼Î»Çý¶¯¡±Ò©Àíѧ£©¡£È»¶ø£¬ÔÚÐí¶àÇéÐÎÏ£¬Ð¡·Ö×ÓÒÖÖƼÁÐèÒªºÍPOIµÄ×ÔÈ»µ×ÎᄎÕùÐÔ͎ᣬÄÑÒÔµÖ´ïºÍά³ÖÓÐÓÃÒÖÖÆPOIËù±ØÐèµÄ¸ß¾Ö²¿Ò©ÎïŨ¶È¡£PROTACµÄ×÷ÓûúÖƲ»ÊÇÓ°ÏìÂѰ׵Ĺ¦Ð§£¬¶øÊǽ鵼°ÐÂѰ׵Ľµ½â£¨¡°ÊÂÎñÇý¶¯¡±Ò©Àíѧ£©£¬²»ÐèҪǿ×÷ÓÃÓÚ»îÐÔλµã£¬Ö»ÐèÒª½éµ¼POIÓëE3·ºËØÅþÁ¬Ã¸µÄ¶ÌÔÝÏ໥×÷Óã¬ÓÕµ¼E3-½µ½â¼Á-POIÈýÔª¸´ºÏÎïµÄÐγÉ£¬´Ó¶ø°ÐÏòһЩ¹Å°åÉÏÒÔΪµÄ¡°²»¿É³ÉÒ©¡±°Ðµã¡£

2) ¹Å°åС·Ö×ÓÒÖÖƼÁ±ØÐè¼á³ÖÆä¾Ö²¿µÄ¸ßŨ¶È²Å»ªÊ©Õ¹ÖÎÁÆ×÷Ó㬶øºã¾Ã¡¢¸ß¼ÁÁ¿µÄÒ©Îï̻¶¿ÉÄÜÔöÌíijЩ²»Á¼·´Ó¦µÄΣº¦£¬²¢ÒýÆðÀÛ»ý¶¾ÐÔ¡£¶øPROTAC¡°ÊÂÎñÇý¶¯¡±µÄ×÷ÓÃģʽ£¬ÆäÑ­»·´ß»¯ÄÜÁ¦Ê¹ÆäÄܹ»´ß»¯¶à¸öPOIµÄ½µ½â£¬Òò´ËÄܹ»ÔÚÑÇ»¯Ñ§¼ÆÁ¿Å¨¶ÈϵִïPOI½µ½âµÄÄ¿µÄ£¬Ö»ÐèÒª½ÏÁ¿µÍµÄ¼ÁÁ¿¾ÍÄִܵïºÍ¼á³ÖÆäҩЧ¡£±ðµÄ£¬ÓÉÓÚPROTAC´ß»¯²¢ÇÒ²»¿ÉÄæµØ½µ½âÖ°©ÂÑ°×£¬PROTAC¾ßÓиü³¤ÆÚµÄÖÎÁÆЧ¹û¡£

3) Ò»Á¬Ê¹ÓÃС·Ö×ÓÒÖÖƼÁÖÎÁÆÒ²¿ÉÄÜÓÕµ¼°ÐÂÑ°×µÄÍ»±ä¼°ÄÍÒ©ÐÔ¡£ÓÉÓÚ¶ÌÔݵİÐÂÑ°×½Ó´¥×ãÒÔʹPOI½µ½â£¬PROTACºÜ¿ÉÄܲ»Ì«ÈÝÒ×Êܵ½warheadÍŽáÇ׺ÍÁ¦½µµÍµÄÍ»±äµÄÓ°Ï죬Òò´Ë£¬PROTACÓпÉÄÜսʤ´ËÀàС·Ö×ÓÒ©ÎïÄÍÒ©ÐÔµÄÎÊÌâ¡£

2 PROTACµÄÉú³¤Àú³Ì

×ÔPROTAC¿´·¨ÓÚ2001ÄêÓÉSakamotoµÈÈËÊ״νÒÏþÒÔÀ´£¬ÒѾ­È¡µÃÁËÐí¶àÖ÷ÒªÉú³¤¡£¶ÔëÄÑÜÉúµÄPROTAC½µ½â¼Á¡¢ÒÔ¼°ÃâÒßµ÷ÀíÑÇ°·Ò©ÎIMiD£©×÷Ϊ·Ö×Ó½º½«µ×ÎïÅþÁ¬µ½E3ÅþÁ¬Ã¸µÄ·¢Ã÷£¬Îª¸ßЧµÄС·Ö×ÓPROTACµÄ·¢Ã÷ºÍ¿ª·¢µÓÚ¨ÁË»ù´¡¡£

ÔÚÒÑÍùµÄ¼¸ÄêÀÂÑ°×½µ½âÁìÓòÂÄÀúÁ˱¬Õ¨Ê½µÄÔöÌí£¬ºÏÀíÉè¼ÆµÄ°ÐÏòÂÑ°×½µ½â¼Á×÷ΪDZÔÚÖÎÁÆÒ©ÎïµÄʱ´úʼÓÚ2019Ä꣬Á½ÖÖPROTACs½øÈëÊ×´ÎÈËÌåÊÔÑ飺ARV-110 £¨NCT03888612£©ºÍARV-471£¨NCT04072952£©£¬»®·Ö°ÐÏòÐÛ¼¤ËØÊÜÌ壨AR£©ºÍ´Æ¼¤ËØÊÜÌ壨ER£©¡£ÏÖÔÚ£¬ÊÇ°ÐÏòÂÑ°×½µ½âµÄ³õʼת»¯½×¶Î£¬ÔÚÕâ¸ö½×¶Î£¬Éè¼ÆÓÃÓÚ½µ½âÖ²¡ÂѰ׵ĶàÖÖ·Ö×ÓÕýÔÚ½øÈëÁÙ´²£¬ÓÐÍûÄܹ»Îª»¼ÕßÌṩÁÙ´²Òæ´¦¡£

PROTACÉú³¤µÄÒªº¦Ï£Íûʱ¼ä±í-1.webp

PROTACÉú³¤µÄÒªº¦Ï£Íûʱ¼ä±í[2]

3 PROTACµÄÁÙ´²Ñо¿Ï£Íû

×Ô2019ÄêÁ½ÖÖС·Ö×ÓPROTAC½µ½â¼Á½øÈëÁÙ´²ÊÔÑéºó£¬Ðí¶àÆäËûС·Ö×ÓPROTACҲ½Ðø½øÈëÁÙ´²Ñо¿£¬Ö÷ÒªÓÃÓÚÖ×ÁöµÄÖÎÁÆÑо¿£¬±ðµÄ»¹Éæ¼°ÃâÒßÑ×Ö¢ÐÔ¼²²¡¡¢Éñ¾­ÍËÐÐÐÔ¼²²¡µÈ˳Ӧ֢¡£×èÖ¹ÏÖÔÚ£¬º£ÄÚÍâ¹²Óнü40¸öPROTACsÒѽøÈëÁËÁÙ´²Ñо¿½×¶Î£¬Ñо¿½Ï¶àµÄ°Ðµã°üÀ¨AR¡¢ER¡¢BTK¡¢EGFR¡¢IRAK4µÈ¡£È»¶ø£¬Ö»¹ÜÓкܺõÄÁÙ´²Ç°Ñо¿Ð§¹û£¬ºÜ´óÒ»²¿·ÖPROTACÔÚÍƽøÈËÌåÁÙ´²ÊÔÑéÀú³ÌÖÐÒ²Óöµ½ÁËÌôÕ½£¬ÏÖÔÚ»¹Ã»ÓÐPROTAC»ñÅúÉÏÊС£

È«ÇòPROTAC¹ÜÏßÁÙ´²Ñз¢Ï£Íû.webp

È«ÇòPROTAC¹ÜÏßÁÙ´²Ñз¢Ï£Íû

4 PROTACµÄÉè¼Æ

PROTACµÄ»ù±¾»¯Ñ§×é³É°üÀ¨£ºÍŽᲢÕÐļE3ÅþÁ¬Ã¸µÄE3ÅäÌ塢͎áPOIµÄÅäÌåºÍÅþÁ¬E3ºÍPOIÅäÌåµÄLinker¡£

PROTACµÄÉè¼Æ£¬Ö÷Òª´ÓÈçϼ¸¸ö·½Ãæ˼Á¿£º

(1) °ÐµãÑ¡Ôñ 

ƾ֤PROTACÆæÒìµÄ¡¢¡°ÊÂÎñÇý¶¯¡±µÄ×÷ÓûúÖÆ£¬°ÐµãµÄÑ¡Ôñͨ³ £¿ÉÒԲο¼ÈçÏÂ6ÏîÔ­Ôò£º

1) ¾­µäµÄ¡°²»¿É³ÉÒ©¡±°Ðµã¡£¹Å°åÉÏ¡°²»¿É³ÉÒ©¡±°Ðµã£¬ÈçKRAS¡¢ÐźŴ«µ¼¼°×ªÂ¼¼¤»îÂÑ°×3 (STAT3) µÈ£¬ÒÑÓб¨µÀÀֳɵØʹÓÃÂÑ°×½µ½â¼Á¾ÙÐÐÁ˽µ½â¡£

2) ÄÍÒ©Í»±ä°Ðµã¡£Ö×Áö°ÐÏòÖÎÁƵÄÄÍÒ©ÐÔͨ³£ÊÇÓÉÓÚÍ»±äµ¼ÖµÄ£¬ÕâЩͻ±ä»òÕßËðº¦Á˹ŰåС·Ö×ÓÒÖÖƼÁÓë°ÐÂÑ°×µÄÍŽáºÍ/»òµ¼Ö°ÐÂÑ°×µÄÌ«¹ý±í´ï£¨Ô­Ôò3£©£¬ÒÔÖÁÓÚÒ©Îï²»¿ÉÔÙ»ñµÃ×ã¹»µÄÁÆЧ¡£PROTAC¿ÉÒÔÀֳɵذÐÏòÕâÀà°ÐÂÑ°×£¬ÈçBTKµÄC481SÍ»±ä£¬BTKÖеÄC481SÍ»±ä×èÖ¹ÁËÁÙ´²ÉÏBTKÒÖÖƼÁµÄ¹²¼ÛÍŽá»îÐÔ£¬µ«ÕâЩÒÖÖƼÁµÄÈõ·Ç¹²¼ÛÍŽáÇ׺ÍÁ¦×ãÒÔÑÜÉúΪ»îÐÔPROTAC¡£

3) »ùÒòÀ©ÔöºÍ/»òÂÑ°×¹ý±í´ï¡£ÈçתÒÆÐÔÈ¥ÊƶԿ¹ÐÔÇ°ÏßÏÙ°© (mCRPC) ¶ÔÐÛ¼¤ËØÊÜÌå (AR) µÄÒ»Á¬ÒÀÀµ£¬ÓÉ¿¹ÐÛ¼¤ËØÖÎÁƵÄÍ»±äºÍ¹ý±í´ïÇý¶¯£¬ÔÙ¼ÓÉϸðеãÒÑÖªµÄÁÙ´²ÓÐÓÃÐÔ£¬Òò´Ë£¬ÁÙ´²Ñо¿ÖеÄPROTACÐí¶àÑ¡ÔñAR×÷Ϊ°Ðµã¡£

4) ¾ßÓвî±ðÒì¹¹Ìå±í´ï»ò¶¨Î»µÄ°Ðµã¡£ÓÉÓÚÂÑ°×¼Ò×åÖÐÒì¹¹ÌåÍŽáλµãµÄ¸ß¶ÈͬԴÐÔ£¬ÓÃС·Ö×ÓÒÖÖƼÁʵÏÖÒì¹¹ÌåÑ¡ÔñÐÔ¾ßÓÐÒ»¶¨µÄÌôÕ½ÐÔ£¬¶øÑо¿·¢Ã÷×ÝȻѡÔñ·ÇÑ¡ÔñÐÔ°ÐÂÑ°×ÍŽáÅäÌåÉè¼ÆµÄPROTAC£¬Ò²¿ÉÄÜÌåÏÖ³öÒì¹¹ÌåµÄÌØÒìÐÔ½µ½â£¬ÀýÈç´ÓË«ÖØCDK4/6ÒÖÖƼÁÖпª·¢³öÑ¡ÔñÐÔCDK4»òCDK6½µ½â¼Á¡£

5) ½ÅÊÖ¼ÜÂѰס£½ÅÊÖ¼ÜÂÑ°×ͨ¹ýÕÐļÆäËûÂÑ°×Ðγɸ´ºÏÎï¶øתµ¼ÐźÅ£¬¶ø²»ÊÇͨ¹ý×ÔÉíµÄ´ß»¯»îÐÔÀ´Ê©Õ¹Æ书Ч£¬Òò´ËºÜÄÑÓùŰåµÄС·Ö×ÓÖ±½Ó°ÐÏò¡£È»¶ø£¬ÕâÀàÂѰ׿ÉÒÔÓÃÂÑ°×½µ½â¼Á°ÐÏò¡£

6) ÂÑ°×Ⱥ¼¯¡£ÂÑ°×ÖÊȺ¼¯ÓëÉñ¾­ÍËÐÐÐÔ¼²²¡ÓйØ£¬°üÀ¨°¢¶û´Äº£Ä¬²¡ºÍÅÁ½ðÉ­²¡£¬ÂÑ°×½µ½âÒªÁìÒ²ÕýÔÚÕâÒ»ÁìÓò¾ÙÐÐ̽Ë÷¡£

(2) E3ÅþÁ¬Ã¸µÄÑ¡Ôñ

ΪÁËÉè¼ÆÓÐÓõÄPROTAC£¬Òªº¦ÊÇҪѡÔñ¶ÔE3ÅþÁ¬Ã¸¾ßÓÐ×㹻͎áÇ׺ÍÁ¦µÄE3ÅäÌ壬²¢ÇÒÔÚ²»Ó°ÏìÆä·ºËØ»¯»îÐÔµÄÇéÐÎÏÂÕÐļ¹¦Ð§»îÔ¾µÄE3ÅþÁ¬Ã¸£¬È»¶øÕâÖÖE3ÅäÌåµÄ¿ÉÓÃÐÔÊÇÓÐÏ޵ġ£ÔÚÈËÀà»ùÒò×éÖбàÂëÁË600¶àÖÖE3ÅþÁ¬Ã¸£¬Æù½ñΪֹֻÓÐԼĪ10ÖÖE3ÅþÁ¬Ã¸±»ÀÖ³ÉÓÃÓÚ°ÐÏòÂÑ°×½µ½â¡£

ÏÖÔÚ£¬°ÐÏòÂÑ°×½µ½â¼ÁÆÕ±éʹÓõÄÁ½ÖÖE3ÅþÁ¬Ã¸ÊÇ von Hippel-Lindau (VHL) ºÍcereblon (CRBN) £¬Ö÷ÒªÔµ¹ÊÔ­ÓÉ°üÀ¨£ºÊ×ÏÈ£¬VHLºÍCRBN¿ÉÒÔʹÓÃÏÖÓеġ¢ÈÝÒ×»ñµÃµÄС·Ö×ÓÍŽáÅäÌ壬ÇÒ¾ßÓÐÊʺÏLinkerÅþÁ¬µÄ½á¹¹Î»µã£»Æä´Î£¬VHLºÍCRBN¿ÉÒÔÎÞаÎȹ̵ؽµ½âÖÖÖÖ°ÐÂÑ°×£»µÚÈý£¬VHLºÍCRBNµÄ±í´ïÏà¶ÔÆձ飬Äܹ»ÊµÏÖ¸ßˮƽµÄϵͳÐÔÂÑ°×½µ½â¡£

³£ÓõĻùÓÚɳÀû¶È°·µÄCRBNÅäÌåºÍ¿ÉÄܵÄLinkerÅþÁ¬·½·¨.webp

³£ÓõĻùÓÚɳÀû¶È°·µÄCRBNÅäÌåºÍ¿ÉÄܵÄLinkerÅþÁ¬·½·¨[3]

³£ÓõÄVHLÅäÌåºÍ¿ÉÄܵÄLinkerÅþÁ¬·½·¨.webp

³£ÓõÄVHLÅäÌåºÍ¿ÉÄܵÄLinkerÅþÁ¬·½·¨ [3]

³ýÁËCRBNºÍVHLÖ®Í⣬ÆäËû³£¼ûµÄE3ÅäÌ廹°üÀ¨IAP¼°MDM2£¬E3ÅþÁ¬Ã¸µÄÐÂÅäÌåµÄ·¢Ã÷ºÍ¿ª·¢Ò²ÕýÔÚ¾ÙÐÐÖУ¬ÈçRNF4¡¢RNF114¡¢DCAF16¡¢KEAP1¡¢DCAF11ºÍFEM1BµÈ¡£ÓÉÓÚ²»¼ÓÇø·ÖµÄϵͳÐÔ°ÐÂÑ°×½µ½â¿ÉÄܵ¼Ö²»¿É½ÓÊܵĶ¾ÐÔºÍÏà¶ÔÏÁÕ­µÄÖÎÁÆÖ¸Êý£¬×éÖ¯ÌØÒìÐÔ»òÖ×ÁöÌØÒìÐÔE3ÅþÁ¬Ã¸µÄÅäÌ忪·¢Êܵ½Ô½À´Ô½¶àµÄ¹Ø×¢¡£Í¨¹ý°ÐÏòÖ×ÁöÌØÒìÐÔE3ÅþÁ¬Ã¸£¬ÌØÒìÐԵؽµ½âÖ×Áö×éÖ¯ÖÐÏà¹ØÂÑ°×£¬Ô­ÔòÉÏ¿ÉÒÔÌá¸ßPROTACµÄÄÍÊÜÐÔ¡£

(3) POIÅäÌåÉè¼Æ

POIÅäÌåµÄÑ¡Ôñ¹ØÓÚPROTACµÄÀÖ³ÉÉè¼ÆÒ²ÊÇÖÁ¹ØÖ÷ÒªµÄ¡£Í¨³££¬Ñ¡ÔñPOIÅäÌåµÄÈܼÁ̻¶ÇøÓò×÷ΪLinkerÅþÁ¬Î»µã£¬ÒÔÖ»¹ÜïÔÌ­LinkerºÍE3ÅäÌå¶ÔPROTAC-POIÍŽáµÄ×ÌÈÅ¡£

PROTACµÄÉè¼Æ¿ÉʹÓÃÒѱ¨µÀµÄ°ÐÂÑ°×ÍŽáÅäÌ壬ÕâЩÅäÌå×î³õ±»Éè¼ÆΪ°ÐÂÑ°×ÒÖÖƼÁ¡£Ëæ×ŶÔеİÐÂÑ°×½µ½âµÄ̽Ë÷£¬ÌØÊâÊǹŰåµÄ¡°²»¿É³ÉÒ©¡±°Ðµã£¬Ê¶±ðеİеã-ÂÑ°×ÍŽáÅäÌåµÄÐèÇóÔöÌí¡£DNA±àÂë¿â (DEL) ÊÖÒÕÊÇÒ»ÖÖ¿ÉÓõÄÂÑ°×½µ½â¼ÁµÄÅäÌåÅжϺͿª·¢µÄÒªÁ죬DELÊÖÒÕɸѡµÄÔ­ÀíÖУ¬ÅäÌåÍŽáλµãºÍÂÑ°×¹¦Ð§»îÐÔÎ޹أ¬ÇÒÔÚûÓиü¶àµÄ½á¹¹Ö§³ÖµÄÇéÐÎÏ£¬Äܹ»ÌṩһÖÖDZÔÚµÄLinkerÅþÁ¬Î»µã£¨¼´DNAÌõÂë±ê¼Çλµã£©¡£DELÊÖÒÕÔÚ·¢Ã÷еķÖ×Ó½º½µ½â¼Á¡¢E3ÅþÁ¬Ã¸ÅäÌåµÈ·½ÃæÒ²ÓÐDZÔÚµÄÓÃ;¡£

(4) LinkerÉè¼Æ

°ÐÂÑ°×ÓëE3ÅþÁ¬Ã¸ÅäÌåÖ®¼äʹÓõÄLinkerÀàÐͺͳ¤¶ÈÊÇÖÁ¹ØÖ÷ÒªµÄ£¬Í¨³£Ê¹Óòî±ð³¤¶ÈµÄÍé»ù»ò¾ÛÒÒ¶þ´¼ (PEG) Linker£¬ÒÔÈ·¶¨°ÐÂѰ׺ÍE3ÅþÁ¬Ã¸Ö®¼äµÄ×î¼Ñ¾àÀë¡£ÓÉÓÚÂÑ°×Ö®¼äµÄ¿Õ¼äλ×裬LinkerÌ«¶Ì»á×èÖ¹¸ßЧÈýÔª¸´ºÏÎïµÄÐγÉ£»Ì«³¤µÄLinker¿ÉÄÜ»áʹÈýÔª¸´ºÏÎïʧȥÂÑ°×½µ½â»îÐÔ¡£ÔÚijЩÇéÐÎÏ£¬LinkerÔÚÈýÔª¸´ºÏÎïÖв»µ«Æðµ½ÅþÁ¬×÷Ó㬻¹¿ÉÒÔÓëÂÑ°×ÍâòÐγɽӴ¥¡£

һЩÑо¿ÒѾ­Ö¤Êµ£¬LinkerµÄ¹¹ÏóÔ¼Êø¿ÉÒÔͨ¹ý½µµÍ×ÔÓɶȻòËø¶¨ÉúÎï»îÐÔ¹¹ÏóÀ´½øÒ»²½Ìá¸ß»îÐÔ¡£¹¹ÏóÏÞÖÆÐÔLinkerÒѱ»¿ª·¢ÓÃÓÚϵÁÐSMARCA2/4½µ½â¼Á¡¢AR½µ½â¼Á¡¢¼°ER½µ½â¼ÁARV-471µÈ¡£±ðµÄ£¬»¹¿Éͨ¹ýLinkerµÄ½á¹¹Éè¼Æ£¬À´µ÷ÀíPROTACµÄÒ©´ú¶¯Á¦Ñ§ÐÔ×Ó¡£

5 PROTACÒ©Î↑·¢µÄÄѵãÓëÌôÕ½

ËäÈ»PROTAC¾ßÓÐÀå¸ïÒ©Îï·¢Ã÷ÁìÓòµÄDZÁ¦£¬È»¶ø£¬ÓÉÓÚÆä½á¹¹ÌØÕ÷µÄ¹ÌÓÐȱÏÝ£¬¶ÔPROTACµÄÁÙ´²×ª»¯×é³ÉÁËÖØ´óÌôÕ½£¬ÏÞÖÆÁËÆäÁÙ´²Ó¦Óãº

1) ÓÉÓÚE3·ºËØÅþÁ¬Ã¸ÔÚÕý³£×éÖ¯ºÍ¼²²¡²¿Î»µÄ·ÇÑ¡ÔñÐÔ±í´ï£¬µ¼ÖÂPROTACµÄÍѰлîÐÔ£¬´Ó¶ø¿ÉÄÜÒýÆð¸±×÷Óõı¬·¢¡£

2) PROTAC·Ö×ÓÁ¿£¨>800 Da£©Ïà±ÈÓڹŰåС·Ö×ÓÒ©ÎïÒª¸ü´ó£¬Í¨³£Ë®ÈÜÐԽϲÍùÍùµ¼Ö½ϵ͵ÄÉúÎïʹÓöÈ¡£

3) PROTACµÄ¸ß¼«ÐÔÍâòÏÞÖÆÁË·Ö×ÓµÄÉø͸ÐÔ£¬¼«´óµØ×è°­ÁËPROTAC·Ö×Ó͸Ï꾡°ûĤºÍÐÄÀíÆÁÕÏ¡£

4) ϸ°ûÄڽϸßŨ¶ÈµÄPROTACÇãÏòÓÚÐγÉPOI-½µ½â¼ÁµÄ¶þÔª¸´ºÏÎ¶ø²»ÊÇÐγÉÈýÔª¸´ºÏÎ±¬·¢HookЧӦ£¬´Ó¶ø½µµÍ°ÐÂѰ׵Ľµ½â»îÐÔ£¬²¢×è°­ÁËÆäÌåÄÚ¼ÁÁ¿µÄºÏÀíÉè¼Æ¡£

PROTACµÄÖ÷Òª¾ÖÏÞÐÔ.webp

PROTACµÄÖ÷Òª¾ÖÏÞÐÔ [4]

6 ÐÂÒ»´úPROTAC

ËäȻͨ¹ý½á¹¹ÐÞÊÎÓÐÍûսʤPROTACµÄijЩÏÞÖÆ£¬µ«Í¬Ê±ÓÅ»¯ÆäÀí»¯ÐÔ×ÓÒÔÄܹ»ÓÐÓõØÔÚÌåÄÚÓ¦Óã¬ÕâÊÇÒ»¸öÖØ´óµÄÌôÕ½¡£ÐÂÒ»´úPROTACµÄÉè¼Æ¿ÉÄܽâ¾öÕâЩÄÑÌ⣬¶ø²»Êǽö½öÒÀÀµÓÚÌ«¹ýµÄ»¯Ñ§ÓÅ»¯¡£ÕâÀàÐÂÒ»´úPROTACÔÚÌض¨×éÖ¯Êܵ½ÍâÔ´ÐÔ»òÄÚÔ´ÐԴ̼¤ºó£¬»Ö¸´POI½µ½âµÄ¹¦Ð§£¬¶øÔÚÆäËû×éÖ¯¼á³ÖÎÞ»îÐÔ״̬£¬´Ó¶øÓÐÍûʵÏָ߶ȰÐÏòÖÎÁÆ£¬ïÔÌ­¸±×÷Óá£

ÀýÈ磺
(1) µã»÷ÊÍ·ÅÐÔPROTAC (Click-release PROTAC)
(2) øÏìÓ¦ÐÔPROTAC (Enzyme-responsive PROTAC)
(3) ¹Èë׸ÊëÄÏìÓ¦ÐÔPROTAC (GSH-responsive PROTAC)
(4) µÍÑõÏìÓ¦ÐÔPROTAC (Hypoxia-responsive PROTAC)
(5) ¹â¼¤»îÐÔPROTAC (Photo-activatable PROTAC)
(6) ·øÉäÏìÓ¦ÐÔPROTAC (Radiation-responsive PROTAC)
(7) »îÐÔÑõÏìÓ¦ÐÔPROTAC (ROS-responsive PROTAC) µÈ

? µã»÷ÊÍ·ÅÐÔPROTACµÄ¿ª·¢ £¬ÓÐÍûսʤ¹Å°åPROTAC·Ö×ÓÁ¿½Ï´óµÄÏÞÖÆ£¬È»¶ø£¬ÓÉÓÚÿ¸öÇ°Ìå·Ö×ÓÌåÏÖ³ö²î±ðµÄPKÐÔ×Ó£¬ÐèҪ˼Á¿ÕâЩǰÌåµÄÌåÍâ·´Ó¦»îÐԺͺÏÊʵķÖ×Ó±ÈÀý¡£

? ¹â¼¤»îÐÔPROTACµÄÒ»¸öÖ÷ÒªÏÞÖÆÒòËØÊÇ×ÏÍâ¹âȱ·¦×ã¹»µÄ×éÖ¯´©Í¸ÄÜÁ¦£¬Õâ×è°­ÁËÕâЩ¹â¼¤»îPROTACÇ°Ò©µÄ¿ª·¢ºÍÓ¦Óá£ÎªÏàʶ¾öÕâ¸öÎÊÌ⣬¿ÆÑÐְԱ̽Ë÷¿ª·¢ÁËÒ»ÖÖÔÚʵÌåÖ×ÁöÖ줻îPROTACÇ°Ò©µÄÌæ»»Õ½ÂÔ£¬Ê¹ÓÃÄÚÔ´ÐÔÌØÕ÷£¬ÈçȱÑõ¡¢GSHºÍROSµÈˮƽÉý¸ßÀ´¼¤»îPROTAC£¬ÒÔʵÏÖ¾«×¼µÄÂÑ°×½µ½â¡£

ËäÈ»ÕâЩҪÁì¾ßÓнϴ󿪷¢Ç±Á¦£¬µ«ÔÚPROTACÇ°Ò©Éè¼ÆÖÐÐèÒªÉè¼ÆÌØÁíÍâÏìÓ¦²¿·Ö£¬²»¿É×èÖ¹µØµ¼ÖÂPROTAC·Ö×ÓÁ¿µÄÔöÌí£¬Õâ¿ÉÄÜ»á¸øËüÃǵijÉÒ©ÐÔ´øÀ´ÐµÄÌôÕ½¡£

ÐÂÒ»´úPROTACÉè¼ÆÖÐʹÓõÄÕ½ÂÔ.webp

ÐÂÒ»´úPROTACÉè¼ÆÖÐʹÓõÄÕ½ÂÔ[4]

ÅäÌåÐÞÊΠ

ÐÂÒ»´úPROTAC»¹¿Éͨ¹ýÅäÌåÐÞÊΣ¬´Ó¶øÑ¡ÔñÐÔ°ÐÏòÌض¨Ï¸°û£¬ÈçÒ¶Ëá (Folate-targeting PROTAC) ¡¢¿¹Ìå (Antibody-PROTAC conjugate) ºÍÊÊÅäÌå (Aptamer-PROTAC conjugate) µÈ¡£

ÓÉÓÚÕâÀàÅäÌåÐÞÊεÄPROTAC£¬Äܹ»Ñ¡ÔñÐÔµØÍŽᰩϸ°ûÍâò±í´ïµÄÌض¨ÊÜÌå»òÉúÎï·Ö×Ó£¬ÓÐÓõؽ«½µ½â¼ÁÌØÒìÐÔµØÔËË͵½Ö×Áö×éÖ¯£¬×î´óÏ޶ȵØïÔÌ­¶Ô¿µ½¡×éÖ¯µÄ̻¶£¬Òò´ËÒѳÉΪÖ×Áöϸ°û°ÐÏòÂÑ°×½µ½âµÄDZÔÚÖÎÁÆÒ©Îï¡£

È»¶ø£¬Éè¼ÆÓÐÓõÄÅäÌåÐÞÊÎPROTACÇ°Ò©ÐèÒª×Ðϸ˼Á¿¼¸¸öÒòËØ£º
? Ñ¡ÔñºÏÊʵÄÅäÌ壬¶ÔÆä°ÐÊÜÌåÌåÏÖ³ö¸ßÇ׺ÍÁ¦ºÍÑ¡ÔñÐÔ£¬ÊÇʵÏÖ×î¼ÑÖÎÁÆЧ¹ûµÄÒªº¦£»
? È·±£Ñ­»·ÎȹÌÐÔ£¬±ÜÃâÔڵִﲡ±ä×é֮֯ǰ¹ýÔç½µ½â»òËðʧ»îÐÔ£»
? ºÏÀíµÄÅäÌåÉè¼Æ£¬Ôö½øÓÐÓÃÊÍ·Å»îÐÔPROTACÄÚ»¯µ½°©Ï¸°û¡£
×ÜÖ®£¬ÐèÒª×Ðϸ¿ØÖÆÊͷŵÄʱ¼äºÍˮƽ£¬ÒÔ×î´óÏ޶ȵØÌá¸ßÖÎÁÆЧ¹û£¬Í¬Ê±Ö»¹ÜïÔ̭DZÔڵIJ»Á¼·´Ó¦¡£

ÄÉÃ׿ÅÁ£µÝËÍϵͳ

±ðµÄ£¬ÄÉÃ׿ÅÁ£µÝËÍϵͳҲ¿ÉÄܳÉΪһÖÖÓÐÓõÄÌæ»»Õ½ÂÔ£¬Èçµ÷ÀíPROTACµÄË®ÈÜÐÔ¡¢Ï¸°ûÉø͸ÐԺ͸ÄÉÆÌåÄÚÒ©´ú¶¯Á¦Ñ§ÐÔ×Ó£¬ÒÔ¼°ÔöÇ¿PROTACÔÚ²¡±ä×éÖ¯ÖеĻýÀÛ£¬¼õÇáÂÑ°×Öʽµ½â¼ÁµÄ×éÖ¯Íâ°ÐÏò¸±×÷Óã¬ÒÔµÖ´ï¸üºÃµÄÖÎÁÆЧ¹û¡£ÓÃÓÚÒ©ÎïµÝË͵ÄÄÉÃ׿ÅÁ£´óÖ¿ɷÖΪÓлúÄÉÃ׿ÅÁ£ºÍÎÞ»úÄÉÃ׿ÅÁ££¬ÓлúÄÉÃ׿ÅÁ£½øÒ»²½·ÖΪ¾ÛºÏÎïÄÉÃ׿ÅÁ£ºÍÖ¬ÖÊÄÉÃ׿ÅÁ£¡£

Ö»¹Ü¾ßÓкܴóµÄDZÁ¦£¬PROTACÄÉÃ׿ÅÁ£µÝËÍϵͳÈÔÈ»ÃæÁÙ×ÅһЩÏÞÖÆÆäÆÕ±éÓ¦ÓõÄÌôÕ½£º

? È·±£Ò©ÎïµÝËÍϵͳÖÐʹÓõÄÔØÌåÖÊÁϵÄÉúÎïÏàÈÝÐÔ£¬Ó¦×ÐϸÆÀ¹ÀºÍÑ¡ÔñÔÚÌåÄÚʹÓÃÇå¾²ÇÒ²»»áÒýÆð²»Á¼·´Ó¦»ò¶¾ÐÔµÄÖÊÁÏ, ÔÚÓÅ»¯Ð§¹ûµÄͬʱȷ±£Æ丱×÷ÓÃÔڿɽÓÊܵĹæÄ£ÄÚ£»

? ÁíÒ»¸öÖ÷ÒªµÄ˼Á¿ÒòËØÊÇÖÊÁ¿¿ØÖƵĿɿ¿ÐÔ£¬ÓÉÓÚÕâЩµÝËÍϵͳÉæ¼°ÖØ´óµÄÅä·½ºÍ¹¤ÒÕ£¬Òò´ËÔÚÕû¸öÉú²úÀú³ÌÖн¨É轡ȫµÄÖÊÁ¿¿ØÖƲ½·¥ÖÁ¹ØÖ÷Òª£»

? ÌØÁíÍâÔØÌåÖÊÁϺÍÒ©Óø¨ÁÏ¿ÉÄÜ»áÔöÌíPROTACµÄÉú²ú±¾Ç®£¬Ó¦ÆÀ¹ÀÉú²ú¹¤ÒյķŴó¿ÉÐÐÐԺͱ¾Ç®Ð§Ò棬ÒÔÈ·±£ÓÐÓõĴó¹æÄ£Éú²ú¶ø²»Ó°Ïì²úÆ·ÖÊÁ¿¡£

×ܽáÓëÕ¹Íû

PROTAC½µ½â¼ÁµÄ¿ª·¢ÔÚÒÑÍùµÄ¼¸ÄêÖлñµÃÁËѸËÙÉú³¤£¬°üÀ¨´ÓÒ©ÎﻯѧÉè¼ÆºÍ½á¹¹ÓÅ»¯£¬¹âÁÙ´²Ç°ÊµÑéµÄ»îÐÔÆÀ¹À£¬ÔÙ¹âÁÙ´²Ñо¿µÄÑéÖ¤¡£ÁÙ´²Ç°Êý¾ÝµÄ±¨µÀ£¬ÓÐÁ¦µØ֤ʵÎúPROTAC¶ÔÆä°ÐµãµÄÌØÒìÐÔ£¬ÒÔ¼°ÒÖÖÆÖ×ÁöÉú³¤µÄ»îÐÔ¡£±ðµÄ£¬ÁÙ´²Ç°Êý¾ÝÅú×¢£¬ÂÑ°×½µ½â¼Á¶ÔС·Ö×ÓÒÖÖƼÁÖÎÁƺ󱬷¢µÄÄÍÒ©ÐÔÍ»±ä¾ßÓлîÐÔ¡£Ö»¹Ü»¹È±·¦×ã¹»ÁÙ´²Êý¾Ý£¬µ«PROTACÒÑÏÔʾ³ö¶ÔÍíÆÚÇ°ÏßÏÙ°©¡¢ÈéÏÙ°©»òÂýÐÔÁÜ°Íϸ°û°×Ѫ²¡£¨CLL£©»¼ÕßµÄÁÆЧ£¬°üÀ¨»®·Ö¾ßÓÐAR¡¢ERºÍBTKÄÍÒ©Í»±äµÄ»¼Õß¡£PROTAC·Ö×ÓµÄÁÆЧºÍÇå¾²ÐÔ£¬ÔÚ¸ü´óµÄ»¼ÕßȺÌåÖоÙÐÐ̽Ë÷ÊǺÜÊÇÓÐÐëÒªÇÒÓÐÒæµÄ¡£

ÓÉÓÚPROTACÑо¿½Ï¶à¼°Ç°Ñصİе㣬°üÀ¨°ÐÏòAR¡¢ER»òBTKµÄARV-110¡¢ARV-471ºÍNX-2127µÈ£¬ÕâЩ°Ðµã´ËÇ°ÒÑÔÚ¼²²¡µÄ·¢²¡»úÖÆÖÐÑéÖ¤ÁËÆä×÷Óã¬ÏÂÒ»²½µÄÒªº¦ÊÇҪȷ¶¨PROTACÊÖÒÕÊÇ·ñÄܹ»ÕæÕýʵÏÖ¾­µäµÄ¡°²»¿É³ÉÒ©¡±°ÐµãµÄ½µ½â¡£ºÃ±È£¬ÏÖÔÚÔÚÁÙ´²IÆÚÑо¿ÖеÄSTAT3½µ½â¼ÁKT-333¡¢KRAS G12D ½µ½â¼ÁASP-3082£¬»®·ÖÓÃÓÚ¸´·¢ºÍ/»òÄÑÖÎÐÔÁÜ°ÍÁöºÍÍíÆÚʵÌåÁö¡¢ÍíÆÚKRAS G12D Í»±äʵÌåÁö»¼ÕßµÄÖÎÁÆ¡£³ýÁËÔÚ°©Ö¢µÄÖÎÁÆÓ¦Óã¬PROTACÊÖÒÕÒ²¿ÉÓÃÓÚ°ÐÏò¼ÓÈëÆäËû¼²²¡Éú³¤µÄÂÑ°×£¬ÀýÈç°ÐÏòIRAK4½µ½âÓÃÓÚ×ÔÉíÃâÒßÐÔ¼²²¡µÄÖÎÁÆ£¬´Ó¶øÌṩ¸ü¹ãµÄÖÎÁÆDZÁ¦¡£

±ðµÄ£¬ÂÑ°×½µ½â¼ÁµÄ°ÐÏòµÝËÍ£¬¿ÉÄÜʵÏÖ×î´óÏ޶ȵØïÔÌ­È«ÉíµÝË͵ÄDZÔÚ¶¾ÐÔ¡£ÏÖÔÚ£¬ÒѾ­±¨µÀµÄÖÖÖÖµÝËÍϵͳ£¬°üÀ¨¿¹Ìå-PROTACżÁªÎïµÈ£¬¿ÉÒÔÔÚÖ×ÁöÖб»¹â¡¢Ò¶Ëá»ò»îÐÔÑõµÈÑ¡ÔñÐÔ¼¤»î£¬ÒÔʵÏÖPROTACµÄ°ÐÏòµÝËÍ¡£

Ö»¹ÜPROTACÔÚÁÙ´²Ç°ºÍÁÙ´²Öж¼ÏÔʾ³öÖÎÁÆDZÁ¦£¬µ«PROTACµÄ¿ª·¢Ò²ÃæÁÙ×ÅÌôÕ½£¬È综ÕßÊÇ·ñ»á¶ÔÂÑ°×½µ½â¼Á±¬·¢ÄÍÒ©ÐÔ¡£ÏÖÔÚ£¬ÁÙ´²Ç°µÄÑо¿±¨µÀÓÐÏÞ£¬Æù½ñΪֹµÄ´ó´ó¶¼ÂÑ°×½µ½â¼ÁÄÍÒ©ÐԵı¬·¢ÊÇͨ¹ýÓ°Ïì·ºËØ-ÂÑ°×øϵһÇеĸı䣬ÀýÈçE2·ºËØÍŽáøµÄ¹¦Ð§Ëðʧ¡¢E3·ºËØÅþÁ¬Ã¸µÄ×é·Ö»òE3ÅþÁ¬Ã¸»îÐԵĵ÷ÀíÒò×Ó£¬¶ø²»ÊÇ°ÐÂѰ׵ĸıä¡£Ò»ÏîÁÙ´²Ç°Ñо¿ÏÔʾ£¬Ò©ÎïÍâÅűÃMDR1µÄÉϵ÷ÊǶÔÂÑ°×½µ½â¼Á±¬·¢ÄÍÒ©ÐԵĻúÖÆÖ®Ò»¡£ÐèÒª¶Ôºã¾ÃʹÓÃÂÑ°×½µ½â¼ÁÖÎÁƵĻ¼Õß¾ÙÐÐÆÀ¹À£¬ÒÔÈ·ÈÏÁÙ´²Ç°ÊӲ쵽µÄÄÍÒ©»úÖÆÊÇ·ñÒ²»á±¬·¢ÔÚÁÙ´²ÖС£

×ܶøÑÔÖ®£¬ÔÚÒÑÍùµÄ¶þÊ®ÄêÀPROTACÂÄÀúÁË´ÓʵÑéÊÒ¹âÁÙ´²Ñо¿µÄÂþ³¤ÂóÌ£¬ÔÚ2019ÄêÊ״νøÈëÁÙ´²¿ª·¢£¬ÆðÔ´ÁÙ´²Êý¾ÝµÄЧ¹ûÅú×¢PROTAC¾ßÓÐÓÃÓÚ°©Ö¢ÖÎÁƵÄDZÁ¦£¬¸ü¶à¹ØÓÚPROTACµÄÁÙ´²Ñо¿ÕýÔÚ¾ÙÐÐÖС£³ýÁËPROTACÖ®Í⣬ÆäËû°ÐÏòÂÑ°×½µ½âÊÖÒÕÒ²ÕýÔÚ¿ª·¢£¬°üÀ¨Í¬Ñù»ùÓÚ·ºËØ-ÂÑ°×øϵһÇеķÖ×Ó½º¡¢¼°»ùÓÚÈÜøϵһÇеÄÈÜøÌå°ÐÏòǶºÏÌå (LYTAC) ºÍ×ÔÊÉ°ÐÏòǶºÏÌå (AUTAC) µÈ£¬ÕâЩÊÖÒÕÀ©Õ¹ÁËTPDµÄ¹æÄ££¬Îª¼²²¡µÄÖÎÁÆÌṩÁËÁÉÀ«µÄÔ¶¾°¡£

²Î¿¼ÎÄÏ×£º

[1] Brandon Dale et al. Advancing targeted protein degradation for cancer therapy. Nat. Rev. Cancer 2021, 21(10): 638-654.
[2] Mikl¨®s B¨¦k¨¦s et al. PROTAC targeted protein degraders: the past is prologue. Nat. Rev. Drug Discov.2022, 21(3): 181-200.
[3] Ale?a Bricelj et al. E3 Ligase Ligands in Successful PROTACs: An Overview of Syntheses and Linker Attachment Points. Front. Chem. 2021, 9: 707317.
[4] Chao Wang et al. New-generation advanced PROTACs as potential therapeutic agents in cancer therapy. Mol. Cancer 2024, 23(1): 110.
[5] Deborah Chirnomas et al. Protein degraders enter the clinic-a new approach to cancer therapy. Nat. Rev. Clin. Oncol. 2023, 20(4): 265-278.

PROTACÑз¢·þÎñƽ̨.webp

×ðÁú¿­Ê±PROTACÒ©ÎïÑз¢·þÎñƽ̨»ã×ÜÁËÄ¿½ñÊ¢ÐеÄÈÈÃŵİбêÂÑ°×ÅäÌ壻½¨ÉèÁËÆÕ±éµÄÈÈÃÅ°ÐÏòÂѰ׸߶ÈÇ׺ÍÁ¦Ð¡·Ö×Ó¼°Ð¡·Ö×ÓƬ¶Ï»¯ºÏÎï¿â£¬ÆÕ±éµÄE3ÅþÁ¬Ã¸¸ß¶ÈÇ׺ÍÁ¦µÄС·Ö×Ó¼°Ð¡·Ö×ÓƬ¶Ï£»½¨ÉèÁËPROTAC Linker¿â¡£ÕâЩ»ýÀ۵Ļ¯ºÏÎï¿â¿ÉÒÔ×ÊÖú¿Í»§¿ìËÙ¸ßЧµØºÏ³É´ó×ڸ߻îÐÔPROTAC·Ö×Ó£¬¼«´óµØÌá¸ß½ÓÄÉPROTACÊÖÒÕ¾ÙÐеÄÒ©ÎïÑз¢Àú³Ì¡£³ýÁË¿ìËٺϳÉÖ®Í⣬×ðÁú¿­Ê±¿ÉÒÔΪ¿Í»§ÌṩPROTACÌåÄÚÍâҩЧÆÀ¼Û¡¢Ò©´ú¶¯Á¦Ñ§Ñо¿ºÍÇå¾²ÐÔÆÀ¼ÛµÈ·þÎñ¡£

×èÖ¹2024Äê6ÔÂ⣬×ðÁú¿­Ê±ÒÑÀÖ³ÉÖúÁ¦6¸öPROTACÒ©Îï»ñÅúÁÙ´²£¬ÁíÍâÓÐ20+PROTACÏîÄ¿ÔÚÑС£

×Éѯ·þÎñ

ÍƼöÔĶÁ£º

ÐÛ¼¤ËØÊÜÌåPROTAC½µ½â¼ÁµÄÌåÍâѪ½¬ÎȹÌÐÔÑо¿
¡¾ÊÓƵ¡¿ÔõÑùÑ¡ÔñºÏÊʵÄÌåÍâassay¾ÙÐÐPROTAC·Ö×Ó¹¹Ð§¹ØϵÑо¿
¡¾ÊÓƵ¡¿PROTACºÍ¹ÑºËÜÕËáÀàÒ©ÎïÑз¢µÄDMPKÒªµã

Ïà¹ØÐÂÎÅ
¡Á
ËÑË÷ÑéÖ¤
µã»÷Çл»
ÍøÕ¾µØͼ
ÓÑÇéÁ´½Ó£ºÌìÓεǼÖÐÐÄ  amjs°Ä½ðɳÃÅ  ×ðÁú¿­Ê±  js1996¹ÙÍø  ²©ÌìÓéÀÖAGÆì½¢Ìü×îÐÂÏûÏ¢  cq9µç×Ó  ÀÖÌìÌÃfun88  ¹ã¶«»á  k8¿­·¢¹ÙÍøÈë¿Ú  cq9µç×Ó  AG¿­·¢k8ÕæÈËÓéÀÖ  PPµç×Ó  tyc131Ì«Ñô¼¯ÍųǠ ca88¹ÙÍø  ca88¹ÙÍø