er a-1

Ginsenoside Ra1 是来自人参的成分。 Ginsenoside Ra1 对缺氧 复氧诱导的蛋白酪氨酸激酶 (PTK) 活化具有显着抑制作用。

Giredestrant tartrate (Estrogen receptor antagonist 1) 是一种新型的、具有口服活性的、有选择性的、有效的的非甾体雌激素受体拮抗剂。Giredestrant tartrate 与 ER 强效结合，导致 ER 无法激活靶向基因的转录，并促使 ER 蛋白降解。Giredestrant tartrate 可用于治疗肿瘤疾病。

TASIN-1 Hydrochloride (TASIN-1 HCl) 是一种截短型 APC 的选择性抑制剂，通过降低细胞胆固醇水平和通过结肠癌细胞中的 ER 应激 ROS JNK 信号传导诱导凋亡细胞死亡来选择性杀死表达截短型 APC 的结肠直肠癌细胞。

Vepdegestrant （ARV-471） 是一种雌激素受体 (ER) α PROTAC 分子，可降解 ER 阳性乳腺癌细胞系中的 ER，DC50 约为 1 nM。它可以通过降解 ER 来降低经典调节的 ER 靶基因的表达并抑制 ER 依赖性细胞系（包括表达 ESR1 变体的细胞系，例如 Y537S 和 D538G）的生长。

Galeterone (VN 124) 是CYP17抑制剂，能够多功能的抗雄激素，在去势抵抗性前列腺癌中，其IC50值为 47 nM。

Fatostatin hydrobromide (Fatostatin A HBr) 是一种 SREBP 活化的特异性抑制剂，可抑制 SREBP-1 和 SREBP-2 的活化。它与 SCAP (SREBP 裂解激活蛋白) 结合，抑制 SREBPs 的 ER-Golgi 易位。它具有抗肿瘤作用，能抑制 ob ob 小鼠的高血糖。它抑制了细胞中成脂基因的转录。

Fatostatin A 是一种SREBP 活化的特异性抑制剂，能够抑制 SREBP-1 和 SREBP-2 的活化。它与 SCAP (SREBP 裂解激活蛋白) 结合，抑制 SREBPs 的 ER-Golgi 易位。它具有抗肿瘤活性，能抑制ob ob 小鼠的高血糖。它抑制细胞中成脂基因的转录。

Nur77 modulator 1 可与Nur77结合，KD 为 3.58 μM。它上调 Nur77 表达，介导Nur77亚细胞定位，诱导Nur77 依赖的内质网应激和自噬，可导致细胞凋亡，Nur77 modulator 1显示出抗肝癌生物活性。

Amino-PEG10-amine is a PEG-based PROTAC linker employed for the conjugation of two mono diethylstilbestrol (DES)-based ligands. This compound offers an alternative approach to the synthesis of highly selective and active ER antagonists, which are crucial for the advancement of endocrine therapy in breast cancer treatment[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].

SNIPER(ER)-110 comprises a cIAP1 ligand and an estrogen ligand connected by a linker. SNIPER(ER)-51 induces estrogen receptor (ER) protein degradation with DC50s of <3 nM and 7.7 nM after 4 h and 48 h, respectively [1].

SNIPER(ER)-87 is a chemical compound composed of a derivative of the inhibitor of apoptosis protein (IAP) ligand LCL161 conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen using a PEG linker. It effectively degrades the ERα protein with an IC50 value of 0.097 μM. Within cells, SNIPER(ER)-87 selectively recruits XIAP to ERα, and XIAP functions as the primary E3 ubiquitin ligase responsible for the degradation of ERα induced by SNIPER(ER)-87[1][2].

PF-06273340 是一种口服具有活力的、具有选择性的外周限制性Trk 泛抑制剂。

(E Z)-Droloxifene 是 (E)-Droloxifene 和 (Z)-Droloxifene 的混合物，其中 (E)-Droloxifene 是一种选择性雌激素受体调节剂。在兔子子宫匀浆实验中，(E)-Droloxifene 结合雌激素受体 (ER) 的 IC50 值为 24 nM。它能够增加未成熟大鼠的子宫重量，并减少雌二醇诱导的幼年大鼠子宫重量增加。此外，(E)-Droloxifene 抑制 17β-雌二醇刺激的 MCF-7、ZR-75-1 和 T47D 人乳腺癌细胞的生长。(Z)-Droloxifene 则由于与 ER 结合较弱，无雌激素或抗雌激素活性。

PROTAC ER Degrader-14 (compound 86) 是一种 PROTAC 类型的 Estrogen Receptor ERR 降解剂，由以下部分组成：E3 泛素连接酶配体 (blue part)(S)-Deoxy-thalidomide、PROTAC Linker (black part) N-Boc-piperazine，以及靶蛋白配体 (red part) ER ligand-6。E3 连接酶加上 Linker 共同构成了 tert-Butyl (S)-4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperazine-1-carboxylate。

PPIA-IN-1 (Compound 20b) 是肽酰脯氨酰异构酶 A (PPIA) 的抑制剂，KD为0.52 μM。它在多种癌细胞系中表现出抗增殖效果，如HCT116的IC50为0.69 μM，阻滞细胞周期于G0 G1期，并显示抗转移活性。此化合物通过增加ROS引起DNA损伤、ER应激及线粒体功能障碍，并通过MAPK通路诱导HCT116细胞凋亡。PPIA-IN-1 在小鼠CT26异种移植模型中展现抗肿瘤活性。

NE-100 hydrochloride (NE-100 HCl) 是选择性sigma-1 受体拮抗剂，IC50为 4.16 nM。它在体内具有抗精神病活性。它也能抑制内质网应激诱导的海马细胞死亡。

KUS121 is a valosin-containing protein (VCP) modulator that inhibits VCP ATPase activity (IC50= 330 nM).1It inhibits cell death, ATP depletion, and upregulation of C/EBP-homologous protein (CHOP) induced by tunicamycin, an inducer of ER stress, in HeLa cells when used at concentrations of 20, 50, and 50 μM, respectively. KUS121 (100 μM) inhibits ATP depletion and cell death induced by oxygen-glucose deprivation (OGD) in rat primary cortical neurons in anin vitromodel of cerebral ischemia.2It reduces infarction volume and increases the latency to fall in an accelerating rotarod test in a mouse model of focal cerebral ischemia induced by transient distal middle cerebral artery occlusion (MCAO) when administered at a dose of 100 mg/kg immediately following occlusion and again at 50 mg/kg following reperfusion. KUS121 (50 mg/kg) inhibits thinning of the retinal outer nuclear layer and preserves visual function in an rd10 mouse model of retinitis pigmentosa.1 1.Ikeda, H.O., Sasaoka, N., Koike, M., et al.Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosaSci. Rep.45970(2014) 2.Kinoshita, H., Maki, T., Yasuda, K., et al.KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletionSci. Rep.9(1)11519(2019)

(+)-(3R,8S)-Falcarindiol 是一种从胡萝卜中得到的聚乙炔，有抗炎、抗肿瘤和抗脂质过氧化活性。它具有抗分歧杆菌作用，对Mycobacterium tuberculosis H37Ra 的 MIC 和 IC50值分别为 24 μM 和 6 μM。

mEH-IN-1 (Compound 62) is a potent inhibitor of microsomal epoxide hydrolase (mEH), with an IC50 value of 2.2 nM. mEH is an α β-fold hydrolase enzyme that is widely expressed in various mammalian tissues, responsible for the hydrolysis of a diverse range of epoxide-containing molecules. This enzyme is primarily localized in the endoplasmic reticulum (ER) of eukaryotic cells. Research involving mEH-IN-1 can contribute to the understanding of preeclampsia, hypercholanemia, and cancer [1].

E6201 (ER-806201) is a potent dual kinase inhibitor targeting MEK1 and FLT3, inhibiting their activities in an ATP-competitive manner. It effectively suppresses MEK1-induced ERK2 phosphorylation (IC50 = 5.2 nM), MKK4-induced JNK phosphorylation (IC50 = 91 nM), and MKK6-induced p38 MAPK phosphorylation (IC50 = 19 nM). E6201 exhibits anti-tumor and anti-psoriasis effects [1] [2].

Estrogen receptor antagonist7 (compound 13) 是高效ER拮抗剂，能够抑制乳腺癌细胞与卵巢癌细胞生长，展现出抗癌及抗子宫营养活性。

LSD1 ER-IN-1 (compound 11g) 是一种有效的 ER 和 LSD1 抑制剂，能够作用于 LSD1 (IC50: 1.55 μM)。LSD1 ER-IN-1 能够高亲和力的选择 Erα 蛋白，α β 比为 7.11。LSD1 ER-IN-1 对 MCF-7 乳腺癌细胞表现出良好的抗增殖效果 (IC50: 8.79 μM)。

Estrogen receptor antagonist4 是一种有效的雌激素受体 (ER) 降解剂。雌激素信号系统在调节细胞生长、分化和凋亡 (apoptosis) 中发挥着重要作用。Estrogen receptor antagonist4 具有研究癌症疾病的潜力。