proteasome inhibitor-1

PSI 是蛋白酶体proteasome 抑制剂。它对原发性渗出性淋巴瘤 (PEL) 细胞的增殖具有抑制作用。它可用于 KSHV 相关淋巴瘤、卡波济氏肉瘤相关疱疹病毒 (KSHV) 感染的研究。

Cereblon modulator 1 是一种 GSPT1 选择性cereblon (CRBN)E3 连接酶调节剂，以分子胶的方式作用。它通过 CRL4CRBN选择性靶向 GSPT1 进行泛素化和蛋白酶体降解。

Proteasome inhibitor IX (PS-IX) 是 Chalcone 的一种衍生物，对20S 蛋白酶体的胰凝乳蛋白酶样活性有抑制作用，IC50约为 1 μM。它抑制 HCT116 p53+ +细胞生长，IC50为 1.49 μM，显示出有效的抗癌活性。

UT-34 是选择性的、具有口服活性的泛雄激素受体拮抗剂和降解剂，能够作用于野生型 AR (IC50:211.7 nM)、F876L-AR (IC50:262.4 nM)、W741L-AR (IC50:215.7 nM)。它与配体结合结构域和功能 1结构域结合，并需要泛素蛋白酶体途径来降解AR。它有抗前列腺癌的能力。

ONX-0914 (PR-957) 是选择性的低分子量多肽-7(LMP7)的抑制剂，LMP7 是免疫蛋白酶体的类糜蛋白酶亚单位。它是分枝杆菌蛋白酶体的非竞争性不可逆抑制剂，Ki 值为5.2 μM。它通过 HSF-1 介导的 p-TEFb 活化激活潜伏的 HIV-1。

Calpeptin 是一种具有细胞穿透性的calpain 抑制剂，也是cathepsin K 抑制剂，其对人血小板 Calpain I 的ID50值为40 nM。

VR23 是一种蛋白酶体抑制剂，对胰蛋白酶样蛋白酶体、糜蛋白酶样蛋白酶体和半胱天冬酶样蛋白酶体的 IC50 分别是1 nM、50-100 nM 和3 μM。

LMTK3-IN-1 是一种有效的 ATP 竞争性狐猴酪氨酸激酶 3 (LMTK3) (Kd=2.5 μM) 抑制剂，通过泛素蛋白酶体途径降解 LMTK3 发挥特性。LMTK3-IN-1 在多种癌细胞系和体内 BC 小鼠模型中展现出抗癌活性。 LMTK3-IN-1（10-20 μM） 可诱导 BC 细胞系凋亡。

DD1 (HUN85111) 是一种蛋白酶体抑制剂，可诱导人髓系肿瘤选择性凋亡。

Proteasome-IN-1 is an inhibitor of proteasome.

(R)-MG-132 (Z-Leu-D-leu-leu-al) 是一种 MG-132 的对映异构体，是一种蛋白酶体 (proteasome) 抑制剂，细胞毒性比 MG-132 弱。

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).

SNIPER(BRD)-1 is a chemical compound composed of a derivative of the IAP antagonist LCL-161 and the BET inhibitor (+)-JQ-1, linked together. It promotes the degradation of BRD4 through the ubiquitin-proteasome pathway and effectively degrades cIAP1, cIAP2, and XIAP with IC50 values of 6.8 nM, 17 nM, and 49nM, respectively[1].

PIN1degrader-1 (Compound 158H9) 是一种脯氨酸顺反异构酶 (Pin1) 抑制剂，具有IC50值21.5 nM。PIN1degrader-1 通过与Pin1的Cys113形成共价键，引起构象变化，降低Pin1稳定性，并导致蛋白酶体依赖的降解。此化合物能抑制多种癌细胞的活力，可应用于癌症研究。

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。

MG-115 (Z-LL-Nva-CHO) 是一种有效且可逆的蛋白酶体抑制剂，对20S 和26S 蛋白酶体的 Ki 值分别为 21 nM 和 35 nM。MG-115 特异性抑制蛋白酶体的胰凝乳蛋白酶样活性，诱导 p53 依赖性细胞凋亡。

MG-262 是一种可逆的蛋白酶体抑制剂，具有多种生物活性。

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).

KZR-616, a first-in-class inhibitor of the immunoproteasome, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP7/mLMP7) subunits of the immunoproteasome. KZR-616 has the potential for the research of multiple autoimmune diseases[1][2]. KZR-616 also inhibits MECL-1 subunit (IC50=623 nM) and constitutive proteasome β5 subunit (IC50=688 nM). KZR-616 maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. KZR-616 (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)[1].KZR-616 is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 and PR-924 [3]. KZR-616 (5 mg/kg; i.v.; dosing was repeated on days 6, 8, 11, and 13) shows efficacy in the anticollagen antibody induced arthritis (CAIA) model[1]. [1]. Johnson HWB, et al. Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide). J Med Chem. 2018 Dec 27;61(24):11127-11143. [2]. Muchamuel T, et al. FRI0296 Kzr-616, a selective inhibitor of the immunoproteasome, blocks the disease progression in multiple models of systemic lupus erythematosus (SLE). Annals of the Rheumatic Diseases 2018;77:685. [3]. Xi J, et al. Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases. Eur J Med Chem. 2019;182:111646.

VCP p97 inhibitor-1, a highly effective compound, inhibits VCP p97 (also known as Cdc48, CDC-48, or Ter94) with an IC 50 of 54.7 nM. This inhibitor induces a disruption in protein homeostasis and interferes with the degradation process of misfolded polypeptides by the ubiquitin-proteasome system (UPS).

Immunoproteasome inhibitor 1 is a highly potent and reversible inhibitor of both immunoproteasome and proteasome activity. It exhibits time-independent inhibitory effects on immunoproteasome subunits β5c, β1i, and β5i, with respective Ki values of 1.18 μM, 0.27 μM, and 1.91 μM. This compound shows promising potential for the treatment of select neoplastic diseases [1].

GSK3494245 (DDD01305143) 是一种有效的、选择性的、口服具有活力的、可在夹在 β4 和 β5 亚基之间的位点结合寄生虫蛋白酶体 (proteasome) 的糜蛋白酶样活性抑制剂，能够作用于 WTL.donovani 蛋白酶体，其 IC50 值为 0.16μM。GSK3494245 表现出良好的生物安全特性。GSK3494245 对人蛋白酶体的糜蛋白酶样活性具有适当的抑制作用 (IC50: 26S=13 μM；富集的 THP-1 提取物 IC50=40 μM)。

20S Proteasome-IN-4 (Compound 7) 是一种能透过血脑屏障的、寄生虫选择性的、具有口服活性的20Sproteasome 抑制剂，对T. b. brucei20S 蛋白酶体的IC50为 6.3 nM。20S Proteasome-IN-4 可用于非洲人类锥虫病的研究。