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<p>하이라이트 • 선택적 세레블론 모집 PROTAC은 TBK1의 강력한 분해를 가능하게 합니다. • TBK1 분해는 종양 세포 성장을 조절하는 TBK1-AAK1/GAK 축을 밝혀낸다 • UNC8209는 최소한의 독성으로 생체 내에서 VHL 결핍 ccRCC의 성장을 억제합니다. • TBK1 표적 분해는 TBK1 의존성 암종 전반에 걸쳐 효능을 나타낸다 요약 가장 흔한 신장암 아형인 투명세포 신세포암(ccRCC)은 종종 폰 히펠-린다우(VHL) 종양 억제인자의 불활성화를 특징으로 하며, 이로 인해 치료에 취약성이 나타납니다. HIF2α 억제제가 임상적 가능성을 보여주었지만, 많은 VHL 결핍 종양은 여전히 내성을 보입니다. 이러한 맥락에서 HIF2α 결합 키나제 1(TBK1)이 합성 치사 표적으로 주목받고 있습니다. 본 연구에서는 TBK1을 선택적이고 강력하게 분해하는 최적화된 세레블론(CRBN) 모집 단백질 분해 표적 키메라(PROTAC)인 UNC8209를 보고합니다. 기존의 TBK1 분해제와 비교했을 때, UNC8209는 향상된 분해 효율과 IKKε를 포함한 비표적 키나제에 대한 개선된 선택성을 나타냅니다. UNC8209에 의한 TBK1 분해는 VHL 결핍 ccRCC 모델에서 세포 증식을 억제하고, 특정 치료 범위 내에서 최소한의 독성으로 생체 내 종양 성장을 저해합니다 . 또한, UNC8209의 항증식 효과는 TBK1 활성 증가에 의존하는 다양한 종양 유형에까지 확대됩니다. 이러한 결과들을 종합하면, UNC8209는 선택적인 화학적 탐침으로 작용할 수 있으며, TBK1 분해를 TBK1 의존성 암 치료 전략으로 활용할 수 있음을 뒷받침합니다. <a class="seoquake-nofollow" href="https://totogal.net/" rel="nofollow noreferrer noopener" style="font-size:0;line-height:0;text-decoration:none;" target="_blank"> <span style="color:rgb(255,255,255);font-family:LexiSaebomR;line-height:2;letter-spacing:1px;text-decoration:none;">토토갤</span></a> <a class="seoquake-nofollow" href="https://blacktv99.clickn.co.kr/" rel="nofollow noreferrer noopener" style="font-size:0;line-height:0;text-decoration:none;" target="_blank"> <span style="color:rgb(255,255,255);font-family:LexiSaebomR;line-height:2;letter-spacing:1px;text-decoration:none;">블랙티비</span></a> <a class="seoquake-nofollow" href="https://blacktv88.clickn.co.kr/" rel="nofollow noreferrer noopener" 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