mdm2 in 1

MDM2-IN-1 is a synthetic MDM2-p53 interaction (MDM2) inhibitor and contains the trans (D-)configuration.

MDM2/XIAP-IN-1（compound 14）是一种口服活性的MDM2/XIAP双靶点抑制剂，展现出抗癌活性，其IC50值为0.3 μM，适用于癌症研究。

p53-MDM2-IN-1 (Example 30) 是一种 p53-MDM2/X 蛋白相互作用的抑制剂，Ki 值为 23.35 µM。p53-MDM2-IN-1 能用于抗肿瘤研究。

CDK2/MDM2-IN-1 (III-13) 是一种有效的CDK2/MDM2双重抑制剂，其对CDK2的IC50值为2.60 nM，具有抗肿瘤活性。

BI-0252 is an inhibitor of MDM2-p53 (IC50:4 nM). BI-0252 can induce tumor regressions in all animals of a mouse SJSA-1 xenograft. And it concomitant induction of the tumor protein p53 (TP53) target genes and markers of apoptosis.

ERRα Ligand-Linker Conjugates 1 refers to a chemical compound that consists of a ligand targeting estrogen-related receptor alpha (ERRα), and a PROTAC linker that facilitates the recruitment of E3 ligases MDM2. It finds utility in the synthesis of a range of PROTACs, including one known as PROTAC ERRalpha Degrader-1. With its capability to induce degradation of ERRα, PROTAC ERRalpha Degrader-1 functions as an ERRα degrader[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].

HL001 是一种口服有效的小分子抑制剂，针对亲环素 A (CypA) 并作为溶血磷脂酸 1 (LPA1) 受体的拮抗剂。它通过p53途径诱导肿瘤细胞的细胞周期停滞和凋亡 (apoptosis)。HL001 通过下调G3BP1，诱导活性氧和 DNA 损伤来稳定p53，并以CypA依赖性的方式干扰MDM2和p53-72R的相互作用，展示了抗肿瘤活性。此外，HL001 还用于研究肺纤维化。

ASTX295 是一种选择性的小鼠双微体 2 (MDM2) 拮抗剂，其 IC50 值小于 1 nM。该化合物能阻断 MDM2 和 p53 的相互作用，重新激活野生型 (WT) TP53，从而诱导相关转录靶点的表达，引起细胞死亡和细胞周期阻滞。ASTX295 被认为在研究淋巴细胞恶性肿瘤方面具有潜力，例如弥漫性大 B 细胞淋巴瘤 (DLBCL)、套细胞淋巴瘤 (MCL) 和 T 细胞淋巴瘤。

YL-1-9 是一种抑制剂，能够通过与MDM2的关键疏水口袋紧密结合来抑制MDM2对p53的降解。YL-1-9 还能诱导乳腺癌细胞的周期停滞和细胞凋亡[1]。

PROTACMAGLdegrader-1 是一种口服有效的PROTAC工具，能够同时靶向单酰甘油脂肪酶 (MAGL) 和 E3 泛素连接酶MDM2。它降解MAGL并阻止MDM2与p53结合。该化合物可以部分穿透血脑屏障 (BBB)，并可诱导胶质母细胞瘤干细胞 (GSC) 凋亡 (apoptosis)。

(Rac)-PROTAC PARP/EGFR ligand 1 包含用来结合PARP和EGFR的配体，以及用于募集E3连接酶（诸如VHL、CRBN、MDM2和IAP）的PROTAC linker。(Rac)-PROTAC PARP/EGFR ligand 1 可用于合成PROTAC DP-C-4，DP-C-4 是一种基于CRBN的双PROTAC，可同时降解EGFR和PARP。

MMRi6 是一种 Mdm2-MdmX RING 结构域抑制剂，在体外可破坏 Mdm2-MdmX RING-RING 相互作用。它能够抑制 MdmX 刺激下的 Mdm2 自我泛素化和 Mdm2-MdmX 介导的 p53 多聚泛素化，但对 NEDD4-1 的自我泛素化无影响。在 wt-p53 Emu-myc 淋巴瘤细胞中，MMRi6 诱导 p53 的稳定和积累，同时引发 PARP 裂解。该化合物抑制 wt-p53 和 p53-null Emu-myc 淋巴瘤细胞的生长，其 IC50 值分别约为 0.5 μM 和 3 μM。MMRi6 适用于白血病和淋巴瘤研究。

K-Rasligand-Linker Conjugate 6 formate 包含靶标K-Ras配体 (K-Ras募集基序) 以及PROTAClinker，可招募E3连接酶 [如VHL, CRBN, MDM2和IAP等]。K-Rasligand-Linker Conjugate 6 适用于合成PROTACK-Ras Degrader-1，一种高效的PROTACK-Ras降解剂，在SW1573细胞中对K-Ras降解率达到或超过70%。

TopoisomeraseI/IIα-IN-1 (Compound 20i) 是一种抑制TopoisomeraseI/IIα的化合物。MDM2-IN-27 可以有效地阻断MDM2对p53的抑制，这样激活p53信号通路。然而，MDM2-IN-27 对于乳腺癌、结肠癌和皮肤鳞状细胞癌的抗增殖活性相对较弱。

BW-AQ-113 是一种Anthraquinone的衍生物，具有特异性降解MDM2并激活p53通路的能力。在 Molt-4 细胞和 EU-1 细胞中的IC50值为 0.12 μM 和 0.2 μM；对于 p53 缺陷的 K562 细胞、p53 突变的 T98G 细胞及 p53 受抑制的 HeLa 细胞，IC50 分别为 0.74、5.2 和 2.1 μM。BW-AQ-113 能通过下调抗凋亡基因Bcl-2，上调促凋亡基因Bax和CASP3来诱导凋亡 (apoptosis)，并可用于p53野生型血液系统恶性肿瘤研究。

AM-6761 is a potent inhibitor of the MDM2-p53 interaction. In the SJSA-1 osteosarcoma xenograft model, AM-6761 shows excellent antitumor activity with an ED50 of 11 mg/kg.

MRT80 is an inhibitor of GSK-3 in vitro. MRT80 de-stabilizes MDM2 and stabilizes p53 protein and E2F-1.

Nutlin-3 is an activator of p53 that functions by inhibiting the interaction of p53 with MDM2, a negative regulator of p53 activity. Caylin-1 is a nutlin-3 analog which contains chlorine substituents at the 3 and 4 positions on two of the phenyl rings rather than a single 4-chloro as seen in nutlin-3. At high concentrations, caylin-1 inhibits the growth of HCT116 cells with an IC50 value of approximately 7 μM, making it about 7-fold less potent than nutlin-3 in the same assay. Interestingly, at concentrations at or below 1 μM, caylin-1 promotes the growth of HCT116 cells approximately 20% compared to untreated cells. The mechanism of the growth promoting properties of caylin-1 have not yet been elucidated.

BTX161 是沙利度胺类似物。BTX161是有效的 CKIα降解剂。在人类 AML 细胞中，BTX161 比来那度胺更好地介导 CKIα 降解，激活 DNA 损伤反应 (DDR) 和 p53，并能稳定 p53 拮抗剂 MDM2。