protaci

PROTAC-I targets steroid hormone receptors for ubiquitination and degradation.

PROTAC IRAK4 degrader-1 (compound I-210) 是一种基于 Cereblon 的PROTAC，由 IRAK4 配体PROTAC IRAK4 ligand-1，E3 连接酶配体Pomalidomide和PROTAC linker AM-Imidazole-PA-Boc组成。

PROTAC IRAK4 ligand-1 is a synthetic ligand for interleukin-1 receptor-associated kinase 4.

Bestatin-amido-Me, a derivative of Bestatin, acts as an IAP ligand and interacts with ABL inhibitor through a linker to produce SNIPER[1].

MV-1-NH-Me, an MV-1-derived IAP ligand, connects to an ABL inhibitor through a linker, resulting in the formation of SNIPER[1].

PROTAC IRAK4 ligand-5 作为PROTAC靶向蛋白配体，主要应用于合成KT-413。

PROTAC IRAK4 ligand-4，一种PROTAC的靶蛋白配体 (Ligand for Target Protein for PROTAC)，展现出抗肿瘤活性。此化合物能够用作合成PROTAC IRAK4 degrader-12的原料。

PROTACIRAK4 degrader-11 (compound 15) 是一种以Cereblon配体为基础的PROTAC，在HEK293细胞中能够诱导IRAK4降解，最大降解率达到96.25%，其DC50为2.29 nM。

PROTACIRAK4 degrader-13 (Degrader 1) 是一种选择性IRAK4 PROTAC降解剂，在PBMCs中的单核细胞和淋巴细胞的DC50分别为0.86 nM和1.1 nM。该化合物显著激活TIR信号，并抑制Imiquimod诱导的银屑病小鼠模型中循环促炎细胞因子的产生。PROTACIRAK4 degrader-13 可用于研究由TLR和IL-1R驱动的中性粒细胞炎症疾病，例如化脓性汗腺炎 (HS) 和特应性皮炎 (AD)。

PROTAC IDO1 Degrader-1 is the first potent IDO1 (indoleamine 2,3-dioxygenase 1) degrader that hijacks IDO1 to CRBN E3 ligase to introduce IDO1 into UPS and eventually achieve ubiquitination and degradation (DC50=2.84 μM). PROTAC IDO1 Degrader-1 moderately improves the tumor-killing activity of H ER2 CAR-T cells[1]. PROTAC IDO1 Degrader-1 (compound 2c) (10 μM; 24 hours) notably decreases IDO1 level induced by IFN-γ[1].PROTAC IDO1 Degrader-1 and IFN-γ (5 ng/mL) are incubated with HeLa cells for 24 h, and a significant dose-dependent degradation is observed. PROTAC IDO1 Degrader-1 combined with chimeric antigen receptor-modified T (CAR-T) cells can improve the tumor-killing activity of HER-2 CAR-T cells[1].PROTAC IDO1 Degrader-1 induces significant and persistent degradation of IDO1 with maximum degradation (dmax) of 93% in HeLa cells[1]. [1]. Hu M, et al. Discovery of the first potent proteolysis targeting chimera (PROTAC) degrader of indoleamine 2,3-dioxygenase 1. Acta Pharm Sin B. 2020;10(10):1943-1953.

PROTAC IRAK4 degrader-4 (US20190192668A1, compound I-127) is a Cereblon-based PROTAC specifically designed to target and degrade interleukin-1 receptor-associated kinase 4 (IRAK4).

PROTAC IRAK4 degrader-5 is a Cereblon-based IRAK4 degrader.

PROTAC IRAK4 degrader-6 is a potent Cereblon-based compound designed to degrade interleukin-1 receptor-associated kinase 4 (IRAK4).

PROTAC IRAK4 degrader-3 is a PROTAC-induced IRAK4 degrader based on von Hippel-Lindau.

PROTAC IRAK3 degrade-1 is a potent and selective degrader of IRAK3 ( IC 50 = 5 nM).

PROTACIRAK4 degrader-2 (Compound 9) 是一种 PROTACIRAK4降解剂，在外周血单个核细胞 (PBMC) 中，降解 IRAK4，DC50为 151 nM。PROTACIRAK4 Degrader-2 在 PBMC 细胞中诱导 IRAK4蛋白水平降低，DC50为 36 nM。PROTACIRAK4 degrader-2 还抑制 PBMC 中多种细胞因子释放。

KT-474 (KYM-001) 是一种靶向白细胞介素-1 受体相关激酶 4（IRAK4）的 PROTAC 降解剂，具有抗肿瘤活性，可用于研究自身免疫疾病、炎症和心血管疾病疾病。

PROTACIRAK3降解剂-1（化合物23）以IC50为5纳摩的浓度选择性地降解IRAK3，表现出高效性。

PROTACIRAK4 ligand-3 为 PROTACIRAK4 degrader-7 配体，适用于癌症研究领域。

PROTACIRAK4 degrader-10 (compound 10) 为基于Cereblon配体的口服活性PROTAC，能在HEK293细胞里实现对IRAK4的最高95.94%的降解效果，其DC50为7.68 nM。