protac crbn degrader 1

PROTAC CRBN Degrader-1 is a chemical compound consisting of a cereblon (CRBN) ligand binding group, a linker, and a von Hippel-Landau (VHL) binding group. It functions as a cereblon (CRBN) degrader[1].

Thalidomide 4-fluoride (E3 ligase Ligand 4) 是一种基于 Thalidomide 的 Cereblon 配体，可用于募集 CRBN 蛋白。它能够利用 linker 与 IRAK4 靶蛋白配体连接，得到 PROTAC IRAK4 degrader-1。

Desmorpholinyl Navitoclax-NH-Me (Desmorpholinyl ABT-263-NH-Me) 是一种 Bcl-xL 抑制剂，这是一种 PROTAC BCL-XL 降解剂,可与 CRBN 配体一起使用以合成 XZ739 [1] [2]。

PROTAC Mcl1 degrader-1 是一种基于 Cereblon 配体的靶向嵌合体的蛋白水解 (PROTAC) ，是选择性的 Mcl-1 抑制剂，通过劫持 CRBN 泛素连接酶与靶蛋白形成三元复合物,诱导的 Mcl-1 泛素化,可用于研究肿瘤。

PROTAC BRD9 Degrader-1 is a leading PROTAC BRD9 chemical degrader with an IC50 of 13.5 nM.

Homo-PROTAC cereblon degrader 1 (compound 15a) 是一种高效 cereblon 降解剂，对 IKZF1 和 IKZF3 的影响很小。

PROTAC CDK9 degrader-2 (compounds 11c) is a potent and selective CDK9 degrader based on PROTAC, with an IC50 of 17 μM in MCF-7 cell lines. Natural product Wogonin binds ubiquitin E3 ligase cereblon (CRBN) via a linker to form PROTAC[1].

K-Ras ligand-Linker Conjugate 1 is a chemical compound that includes a ligand for K-Ras and a PROTAC linker, facilitating the recruitment of E3 ligases VHL, CRBN, MDM2, and IAP. It can be utilized in the synthesis of PROTAC K-Ras Degrader-1, a highly effective K-Ras degrader that achieves ≥70% degradation efficacy in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 2 is a chemical compound that includes a ligand for K-Ras and a PROTAC linker. This compound is capable of recruiting E3 ligases like VHL, CRBN, MDM2, and IAP. It is utilized in the synthesis of PROTAC K-Ras Degrader-1, which is a highly effective PROTAC K-Ras degrader with a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 3 (Compound 001371) is a chemical compound that consists of a ligand for K-Ras recruiting moiety and a PROTAC linker, responsible for recruiting E3 ligases (e.g., VHL, CRBN, MDM2, and IAP). This compound is essential in the synthesis of PROTAC K-Ras Degrader-1, a potent PROTAC K-Ras degrader that demonstrates a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 4 is a chemical compound that combines a ligand for K-Ras recruiting moiety with a PROTAC linker. This linker is responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. The compound has the potential to be used in the synthesis of PROTAC K-Ras Degrader-1, a powerful degrader of K-Ras that has been shown to exhibit a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 5 is a chemical compound that combines a ligand for the K-Ras recruiting moiety with a PROTAC linker. This linker is responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. The K-Ras ligand-Linker Conjugate 5 plays a crucial role in the synthesis of PROTAC K-Ras Degrader-1, a highly potent K-Ras degrader. In SW1573 cells, this degrader exhibits an impressive degradation efficacy of ≥70% [1].

PROTAC BRD2 BRD4 degrader-1 (compound 15) serves as a potent, selective degrader of BET proteins BRD4 and BRD2, achieving rapid, reversible, and unexpectedly selective elimination of BRD4 and BRD2 compared to BRD3. Its efficacy in suppressing solid tumors manifest with minimal cytotoxic effects. This compound comprises a BET inhibitor, a connecting linker, and thalidomide as the ligand for cereblon (CRBN) cullin 4A[1].

TD-165 是一种基于 PROTAC 技术的 CRBN 降解剂。它包括一个 CRBN 配体结合基团，一个 linker 和一个 VHL 结合基团。

Thalidomide-C2-amido-C2-COOH is a compound that includes a CRBN ligand for the E3 ubiquitin ligase, as well as a linker. It is utilized in the development of PROTAC CDK2 9 Degrader-1[1].

JQ dS-4 是一种针对Brahma-related gene 1 (BRG1) BRM SMARCA4 的降解剂 (PROTAC®; DC50 范围为9 - 390 nM，适用于胶质瘤模型和细胞系)。该化合物通过连接器将BRG1抑制剂与cereblon (CRBN) E3连接酶配体结合。在HSJD-DIPG007和SU-DIPGXIIIP细胞中，48小时和72小时后BRG1被完全降解，并且能减少包括H3K27M胶质瘤、前列腺、甲状腺和涎腺癌细胞系的活性。

PROTAC TRIB2 degrader-1 (Compound 5k) 作为一种选择性TRIB2降解剂，通过CRBN依赖的泛素-蛋白酶体途径有效诱导TRIB2的降解。此化合物能够抑制细胞增殖并诱导细胞凋亡(apoptosis)，有望在癌症研究中发挥重要作用。

PROTAC JNK1-targeted-1 (PA2) 是一种 JNK1 PROTAC 降解剂，具有 DC50 值为 10 nM。此化合物能够降低纤连蛋白水平，并可用于肺纤维化研究。(Pink: JNK1 inhibitor; Black: linker; Blue: CRBN Ligand)

PROTAC CARM1 IKZF3 degrader-1 (Compound 074) 抑制CARM1并减少其底物BAF155的甲基化。它是通过CRBN依赖途径降解IKZF 1 3的PROTAC降解剂，抑制MYC蛋白表达，以减缓多发性骨髓瘤细胞的增殖，并诱导H929细胞凋亡 (apoptosis)。此外，该化合物能够克服对免疫调节药物（IMiD，如泊马度胺）的耐药性，适用于癌症和免疫学研究。(Pink: ligand for target protein CARM1 IKZF3 ligand 1; Active form of target protein ligand: EZM 2302; Black: linker; Blue: ligand for E3 ligase Cereblon Thalidomide 4-fluoride)

ROR1ligand-1 (9-1) 是 PROTAC ROR1 降解剂-1 的特定配体。通过与 VHL型或 CRBN 配体结合，开发并合成了第一个选择性和高效的 ROR1 PROTAC 分子。

PROTAC FGFR1 degrader-1 (compound S2H) 是一种专门靶向FGFR1的PROTAC降解剂，其在 KG1a 细胞中具有 IC50=26.81 nM 和 DC50=39.78 nM。该化合物由 CRBN 型 E3 连接酶配体 (blue part) Pomalidomide、靶蛋白配体 (red part) FGFR1 ligand-1 以及 PROTAC 链接子 (black part) 9-Bromononanoic acid 组成，其中 E3 连接酶配体与链接子共同构成偶联物 E3LigaseLigand-linker Conjugate 164。

CDK9 Antagonist-1 (compounds 11c) is a potent and selective CDK9 degrader based on PROTAC, with an IC50 of 17 μM in MCF-7 cell lines. Natural product Wogonin binds ubiquitin E3 ligase cereblon (CRBN) via a linker to form PROTAC[1]. CDK9|17 μM (IC50, MCF-7 cells) [1]. Bian J , et al. Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity. Bioorg Chem. 2018 Dec;81:373-381.

LSN3106729 hydrochloride, the metabolite of Abemaciclib , is a CDK inhibitor with antitumor activity. LSN3106729 hydrochloride and a CRBN ligand have been used to design PROTAC CDK4 6 degrader[1].

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.