proteasome in 1

Proteasome-IN-1 is an inhibitor of proteasome.

PARP-1/Proteasome-IN-1 (compound 42i) 是一种能够同时抑制 PARP-1 和蛋白酶体的化合物，对乳腺癌表现出显著的抑制效果。通过下调 BRCA1 和 RAD51 的表达，PARP-1/Proteasome-IN-1 抑制了同源重组修复功能，并诱导细胞凋亡 (apoptosis)。

PROTAC 20S proteasomesubunit β5 degrader 1 (compound 12f)，一种针对20S蛋白酶体亚基β5的靶向降解剂，在FaDu细胞中表现出0.11 μM的DC50值。此化合物能在FaDu和KM3/BTZ细胞中干扰细胞周期，促进细胞凋亡(apoptosis)，并有效抑制细胞的增殖与迁移。此外，PROTAC 20S proteasomesubunit β5 degrader 1 还可用于研究咽癌和多发性骨髓瘤中对Bortezomib的耐药性。

Proteasome-activating peptide 1 TFA 是一种肽类蛋白酶体激活剂，能显著增强胰凝乳蛋白酶样蛋白酶体的催化活性，进而提升体外及培养环境中的蛋白质水解效率。此外，Proteasome-activating peptide 1 TFA 还能有效阻止肌萎缩侧索硬化症细胞模型内的蛋白质聚集现象。

Proteasome-activating peptide 1 是一种肽，其作用是提升胰凝乳蛋白酶样蛋白酶体（proteasome）的催化活性，有效增强体外及细胞培养环境下的蛋白质降解效率。此外，该肽能阻止肌萎缩侧索硬化症（Amyotrophic Lateral Sclerosis, ALS）细胞模型中蛋白质的过度聚集。

Proteasomeβ2c/i-IN-1（compound 37）为针对β2c和β2i亚基的选择性蛋白酶抑制剂。

HM90822 是一种新型合成凋亡蛋白（IAP）拮抗剂，通过蛋白酶体依赖性降解含有BIR2/3结构域的IAPs诱导人胰腺癌细胞凋亡。HM90822 抑制对 HM822 敏感的 Panc-1 和 BxPC-3 细胞中 XIAP 和 cIAP1/2 蛋白的表达，诱导 IAP 泛素化并促进蛋白酶体依赖性 IAP 降解。

S119-8 是一种广谱甲型和乙型流感病毒抑制剂，抑制多种乙型流感病毒和耐奥司他韦的甲型流感病毒。

Radicicol(Monorden，根赤壳菌素)是一种抗真菌抗生素，也是热休克蛋白90（Hsp90）的强效抑制剂（IC50 = 1 μM），通过结合Hsp90的ATP结合口袋，导致Hsp90被蛋白酶体降解。此外，Radicicol还抑制多种肿瘤细胞系的生长和增殖。它还具有抗疟疾活性，并可作为脂肪和肥胖相关蛋白（FTO）的抑制剂。Radicicol通过阻断p38激酶信号通路和NF-κB/Rel抑制iNOS基因表达

Rpn11-IN-1 is an effective and selective inhibitor of proteasome subunit Rpn11 (IC50: 390 nM).

SPDP-C6-NHS ester 是一种基于烷基/醚的连接子，用于 PROTAC 合成。PROTAC 分子由两种配体通过连接子连接：一端配体招募 E3 泛素连接酶，另一端结合靶蛋白。SPDP-C6-NHS ester 利用泛素-蛋白酶体系统实现靶蛋白的选择性降解。

Boc-C1-PEG3-C4-OBn (PROTAC Linker 15) is a PEG-based PROTAC linker employed in the synthesis of various PROTACs, including PROTAC SGK3 degrader-1. PROTACs are composed of two distinct ligands connected by a linker; one ligand binds to an E3 ubiquitin ligase, while the other specifically interacts with the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs can selectively degrade target proteins[1].

Boc-C1-PEG3-C4-OH is an Alkyl/ether-based PROTAC linker utilized in the synthesis of PROTACs, which are characterized by their structure comprising two distinct ligands tethered by a linker. One ligand of PROTACs binds to an E3 ubiquitin ligase, while the other binds to the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs facilitate the targeted degradation of specific proteins[1].

Phthalimide-PEG3-C2-OTs (Compound 5) is a PROTAC linker composed of PEGs. It is utilized in the synthesis of various PROTACs, which involve the connection of two distinct ligands through a linker. One ligand is specific for an E3 ubiquitin ligase, while the other ligand is designed for targeting the specific protein of interest. Through leveraging the intracellular ubiquitin-proteasome system, PROTACs are capable of selectively degrading target proteins [1].

Phthalimide-PEG4-MPDM-OH, a PROTAC linker with a PEGs composition, has applications in the synthesis of various PROTACs. These PROTACs consist of a linker connecting two distinct ligands: one binds to an E3 ubiquitin ligase, while the other binds to the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs selectively induce the degradation of target proteins [1].

Phthalimide-PEG4-PDM-OTBS is a PROTAC linker comprised of polyethylene glycols (PEGs). This compound is utilized in the synthesis of a range of PROTACs, which consists of two distinct ligands connected by a linker. One ligand binds to an E3 ubiquitin ligase, while the other ligand binds to the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs selectively degrade target proteins[1].

(±)15-HETE是一种二十烷酸类化合物，具有内在生物活性，并作为多种其他生物活性脂质衍生衍生物生物合成的关键酶促前体。此外，(±)15-HETE可作为蛋白水解靶向嵌合体（PROTAC）连接子，用于化学合成多种设计用于靶向蛋白降解的PROTAC分子。

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。

TrxR/EGFR-IN-1 (Compound L1Au2) 是一款TrxR/EGFR的抑制剂，针对吉非替尼敏感及耐药的肺癌均展示出活性，有效抑制肿瘤增殖并诱导细胞凋亡 (apoptosis)。该化合物通过自噬溶酶体和蛋白酶体途径加速GPX4蛋白的降解，从而引发铁死亡 (ferroptosis)。此外，TrxR/EGFR-IN-1 还可以诱发内质网应激并引发免疫原性细胞死亡，因此适用于吉非替尼耐药肺癌的研究。

MS9024 是一种 DNA 甲基转移酶 1 (DNMT1) 的降解剂，它通过泛素-蛋白酶体途径在 HCT116 细胞中降解 DNMT1，其 DC50 为 35 nM（在 MDA-MB-468 和 H1299 中的 DC50 分别为 254 nM 和 101 nM）。此外，MS9024 对 DNMT1 的抑制作用，IC50 为 0.43 μM。

c-Met degrader-1 (Compound H11) 是一种口服活性的c-Met降解剂，利用泛素蛋白酶体系统进行降解，具有抗肝细胞癌 (HCC) 的活性，并能抑制 MHCC97H 异种移植瘤的生长。这种化合物可以抑制 HCC 细胞的增殖，阻止细胞周期进程，并诱导细胞凋亡 (Apoptosis)。此外，c-Met degrader-1 有可能克服细胞对 Ib 型 c-Met 抑制剂产生的耐药性。

Steviol (NSC-226902) 是一种甜菊糖甙的主要代谢物。它能降低 AQP2 的表达，并促进 AQP2 的降解，从而减缓肾囊肿的生长。

Potent and selective BTK Degrader (IC50 = 5.1 nM); degrades BTK in a proteasome- and CRBN-dependent manner. Suppresses BTK signaling and proliferation in mantle cell lymphoma (MCL) cells by degrading BTK, IKFZ1, and IKFZ3 (3 validated targets in B-cell malignancies). Also degrades Ibrutinib (Cat. No. 6813) -resistant C481S-BTK mutant cancer cells. Exhibits no binding against a panel of 468 kinases at 1 μM. Reduces tumor burden and extends survival in lymphoma patient-derived xenograft models.

C6 urea ceramide is an inhibitor of neutral ceramidase.1 It increases total ceramide levels in wild-type mouse embryonic fibroblasts (MEFs) and in HT-29 colon cancer cells but not in MEFs lacking neutral ceramidase. It inhibits proliferation of, and induces apoptosis and autophagy in HT-29, but not non-cancerous RIE-1, cells when used at concentrations of 5 and 10 μM. C6 urea ceramide decreases total β-catenin, increases phosphorylated β-catenin, and induces colocalization of β-catenin with the 20S proteasome in HT-29 and HCT116, but not RIE-1, cells. It reduces tumor growth and increases C16, C18, C20, and C24 ceramide levels in tumor tissue in an HT-29 mouse xenograft model when administered at doses of 1.25, 2.5, and 5 mg/kg for five days. |1. García-Barros, M., Coant, N., Kawamori, T., et al. Role of neutral ceramidase in colon cancer. FASEB J. 30(12), 4159-4171 (2016).