protac errα degrader 3

PROTAC ERRα Degrader-3 is a highly effective and selective von Hippel-Lindau-based ligand that efficiently degrades the ERRα protein. At a concentration of 30 nM, this compound exhibits a remarkable degradation capability, reducing the ERRα protein levels by >80%. Importantly, PROTAC ERRα Degrader-3 shows no activity against the ERRβ and ERRγ proteins.

PROTAC BRAF-V600E degrader-1 (Compound 23) 选择性地诱导 BRAF-V600E 的降解，而不是野生型 BRAF。

Gefitinib-based PROTAC 3 通过 linker 将 EGFR 结合元件与 von Hippel-Lindau 配体结合，在 HCC827（外显子 19 del）和 H3255（L858R 突变）细胞中诱导 EGFR 降解，DC50 分别为 11.7 和 22.3 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。

Homo-PROTAC pVHL30 degrader 1 是一种基于 PROTAC 的 pVHL30 降解剂。

PROTACSOS1 degrader-8 (Compd 10) 是SOS1的PROTAC降解剂，其中包含SOS1配体（红色）、连接子（黑色）和E3连接酶配体（蓝色）。

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（结构备注：(蓝色：Cereblon配体，黑色：连接体；粉红色：IRAK4抑制剂)）。

PROTACATRdegrader-2 (Compound 8i) 作为一种有效的ATRPROTAC降解剂，能够在急性髓系白血病 (AML) 细胞 MV-4-11 和 MOLM-13 中分别以 DC50 值 22.9 nM 和 34.5 nM 降解 ATR。此外，PROTACATRdegrader-2 还能诱导细胞凋亡（apoptosis）并抑制 AML 细胞的增殖。在小鼠体内，该化合物示出了优良的药物代谢动力学属性及显著的抗AML肿瘤活性。 (Pink: ATRligand; Blue: E3 ligase ligand Lenalidomide; Black: linker)

PROTACFLT-3degrader 4 是一种口服活性强的 CRBN 基于的 FLT3-PROTAC 降解剂，能够通过泛素-蛋白酶体系统有效降解 FLT3-ITD。此化合物对 FLT3-ITD 突变的急性髓性白血病 (AML) 细胞展现出高度选择性。

PROTAC SOS1 degrader-8 (Compd 1) 是一种用于降解SOS1的PROTAC分子（Red: SOS1 Ligand, Black: linker, Blue: E3 ligase ligand）。

PROTAC CDK9 Degrader-1 是一种选择性 CDK9 降解剂，是由Cereblon 配体和CDK 配体相连的PROTAC。

PROTACeDHFR Degrader-1是一种高效的PROTAC，针对eDHFR-YFP和多种POI（如YFP、荧光素酶）具有显著的降解作用。

PROTACBRD4 Degrader-21 (Comp 74)为BRD4降解剂，其在小鼠荷瘤异种移植模型中展现出显著抑制肿瘤生长的能力，适用于抗癌研究。

PROTACPTPN2 degrader-2（例187B）TFA 作为PTPN2降解剂，展现出对癌症及代谢性疾病研究的潜在效用。

PROTACTG2 degrader-2（compound 7）是一种针对Transglutaminase 2（TG2）的选择性竞争性降解剂，其Kd值大于100 μM。该化合物能有效抑制卵巢癌细胞的迁移，并降低其TG2表达水平，因此可作为卵巢癌研究的工具。

PROTACBRD9 Degrader-2是针对癌症研究的BRD9双功能性降解剂。

PROTAC BRD4 Degrader-10, also known as compound 8b, is a dual ligand-based PROTAC that combines ligands for von Hippel-Lindau and BRD4. To degrade the BRD4 protein in PC3 prostate cancer cells, PROTAC BRD4 Degrader-10 can be conjugated with STEAP1 and CLL1 antibodies, with respective DC 50 values of 1.3 nM and 18 nM.

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

PROTACAxl Degrader 2 是一种有效的选择性 PROTACAxl 降解剂，IC50为 1.61 µM。PROTACAxl Degrader 2 显示出体外抗增殖活性、抗迁移活性。PROTACAxl Degrader 2 诱导巨泡式细胞死亡 (mehuosis)。

PROTACBcl-xL degrader-3 是一种有效的 PROTACBcl-xL 降解剂。

PROTACBRD4 Degrader-19 (化合物 176)，一种针对BRD4蛋白的PROTAC，具有可靶向降解BRD4蛋白的特性，主要应用于癌症研究。

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。

PROTACBRD4Degrader-7 是一种有效的溴结构域BRD4降解剂，对 BRD4-BD1 和 BRD4-BD2 的IC50分别为 15.5 和 12.3 nM。

PROTAC BRD4 Degrader-15 is a chemical compound consisting of a PROteolysis TArgeting Chimera (PROTAC) linked to ligands specific to von Hippel-Lindau and BRD4. It exhibits an IC50 of 7.2 nM for BRD4 BD1 and 8.1 nM for BRD4 BD2. Additionally, PROTAC BRD4 Degrader-15 demonstrates potent degradation activity against the BRD4 protein in PC3 prostate cancer cells.

PROTAC BRD4 Degrader-5 is a PROTAC-based BRD4 degrader. PROTAC BRD4 Degrader-5 can potent degrade BRD4 in HER2 positive and negative breast cancer cell lines[1].

PROTAC ERα Degrader-2 comprises a cIAP1 ligand binding group, a linker and an estrogen receptor α (ERα) binding group. PROTAC ERα Degrader-2 is an ERα degrader. Maximal ERα degradation at 30 μM concentration in human mammary tumor MCF7 cells. Degradation inducers based on cIAP1 are called specific and non-genetic IAP-dependent protein erasers (SNIPERs)[1].

PROTAC BET degrader-2 is a highly potent degrader of Bromodomain and Extra-Terminal (BET) proteins, with an IC50 of 9.6 nM.

PROTAC FAK degrader 1 is a selective and potent degrader of focal adhesion kinase (Fak) with an IC50 of 6.5 nM.

PROTAC Mcl1 degrader-1 induces the ubiquitination and proteasomal degradation of Mcl-1 by introducing the E3 ligase cereblon (CRBN)-binding ligand pomalidomide to Mcl-1 inhibitor S1-6 with μM-range affinity. PROTAC Mcl1 degrader-1, a proteolysis targeting chimera (PROTAC), is a potently and selectively Mcl-1 inhibitor with an IC50 of 0.78 μM.

PROTAC BRD4 Degrader-2 is an efficacious degrader of PROTAC BRD4(BRD4 BD1,IC50 of 14.2 nM).

PROTAC Sirt2 Degrader-1 is a SirReal-based PROTAC, acts as a Sirt2 degrader, composed of a highly potent and isotype-selective Sirt2 inhibitor, a linker, and a bona fide cereblon ligand for E3 ubiquitin ligase. PROTAC Sirt2 Degrader-1 shows an IC50 of 0.25 μM for Sirt2, with no effect on Sirt1 Sirt3 (IC50s > 100 μM)[1].

PROTAC Bcl2 degrader-1 is a PROTAC, which potently and selectively induces the degradation of Mcl-1 (IC50: 11.81 μM) and Bcl-2 (IC50: 4.94 μM; DC50: 3.0 μM).

PROTAC MDM2 Degrader-3 is a compound that leverages PROTAC technology to degrade MDM2. It consists of a highly effective MDM2 inhibitor, a linker, and the MDM2 ligand for E3 ubiquitin ligase[1].

PROTAC BRD4 Degrader-3 is an efficacious degrader of PROTAC BRD4.

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].

PROTAC ER Degrader-2 serves as a synthesis intermediate for the production of PAC, a compound that incorporates the ADCs linker and PROTACs, which are subsequently conjugated to an antibody. PAC, exhibits a greater capability to degrade estrogen receptor-alpha (ERα) compared to PROTAC (without the presence of an antibody)[1].

PROTAC ER Degrader-3, an intermediate for the synthesis of PAC, specifically compound LP2. PAC serves as the linker for ADCs and PROTACs that are conjugated to an antibody. Notably, when PAC is conjugated to an antibody, it exhibits enhanced degradation of estrogen receptor-alpha (ERα) compared to PROTAC alone [1].

PROTAC RIPK degrader-2 is a nonpeptidic PROTAC ,and potently targets serine-threonine kinase RIPK2 and has highly selective for RIPK2 degradation.

PROTACTYK2 degrader-1 (CPD-155), 作为TYK2的PROTAC靶向降解剂，其Dmax超过60%。 (Srtucture Note: PINK, TYK2 ligand 1; Blue, VHL ligand Thalidomide; Black, linker)

PROTACpan-IAP degrader-1 (Compound 9) 是一种 pan-IAPPROTAC 降解剂。PROTACpan-IAP degrader-1 在 MM.1S 细胞中降解 XIAP、cIAP1 和 cIAP2 的 DC50分别为 0.7、2.4 和 6.2 nM。

PROTACAR-NTD antagonist 1 (compound 18) 是一款针对雄激素受体AR-V7变体的PROTACs，它特异性地拮抗AR的N末端结构域 (AR-NTD)，能有效诱导前列腺癌细胞凋亡，并在VCaP细胞中以1 μM 和 5 μM的浓度分别实现了62.2%和71.1%的AR-V7蛋白降解率。

PROTACHer3 Degrader-8（Compound PP2）是一类PROTAC，能在体外及细胞实验中降解Her3蛋白，适用于HER家族蛋白调控的疾病研究。

PROTAC CRABP-II Degrader-2 is a potent cIAp1-based degrader of cellular retinoic acid binding protein (CRABP-II).

PROTACIRAK4 degrader-7 (Compound I-417) 是一种具有口服活性的 PROTACIRAK4降解剂，具有抗肿瘤效果。

PROTAC STING Degrader-2 是针对 Stimulator of interferon genes (STING) 的蛋白质降解剂，具有DC50为0.53 μM的活性。它通过同时与STING蛋白和E3泛素连接酶共价结合，诱导STING蛋白的降解。该化合物可用于研究STING在自身炎症和自身免疫性疾病中的作用 (PINK:STINGbinder ; Blue: VHL ligand ; Black: linker)。

PROTAC EGF R degrader 10 (Compound B56) 是一种针对表皮生长因子受体 (EGFR) 的 PROTAC 降解剂，其 DC50 小于 100 nM。它可以结合 CRBN-DDB1，Ki 为 37 nM。PROTAC EGF R degrader 10 能降解 EGFR、粘着斑激酶 (FAK) 和 RSK1，并有效抑制 BaF3 野生型和 EGFR 突变体的细胞增殖，IC50 小于 150 nM。

PROTACERα Degrader-7 (compound i-320) 作为一种高效的雌激素受体 α (estrogen receptor alpha (ERα)) PROTAC降解剂，其 DC50 值仅为0.000006 µM。该化合物具备小分子 LBM 部分与配体 ERBM 的连接，其中配体 ERBM 能特异性地结合ERα，并且含有苯并稠合部分以及饱和的6元碳环或杂环结构。

PROTACSOS1 degrader-5 (compound 4) 作为高效的PROTACSOS1降解剂，显示出 DC50 为 13 nM。此外，PROTACSOS1 degrader-5 在抑制 NCI-H358 细胞增殖方面表现出色，其 IC50 达到 5 nM。