mdm2-in-1

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

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。

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。

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。

NSC405640 is a highly effective compound that inhibits the interaction between MDM2 and p53 proteins. Furthermore, it can restore the structural integrity of p53 molecules affected by mutations. Notably, NSC405640 exhibits selectivity in inhibiting the growth of cell lines that possess the normal, unmutated form of the p53 protein [1].

Milademetan (DS-3032) tosylate hydrate，一种特异性、具口服活性的MDM2抑制剂，主要研究用途包括急性髓系白血病和实体肿瘤。它能诱导G1细胞周期阻滞、衰老和凋亡。

MI-1061 TFA 是一种有效、口服生物可用、化学稳定性高的MDM2(MDM2-p53 互作) 抑制剂，具有低纳摩尔级别的抑制活性（IC50=4.4 nM；Ki=0.16 nM）。它能在小鼠SJSA-1 异种移植瘤组织中激活p53并诱导凋亡，展现出抗肿瘤活性。

MDM2 4-p53-IN-2 (2q) 是一种有效的双重 MDM2 MDM4抑制剂和 p53激活剂，作用于 MDM2-p53 和 MDM4-p53 复合物的 IC50值分别是 70.7 nM 和 81.4 nM。MDM2 4-p53-IN-2 可以调控细胞周期，诱导细胞凋亡(apoptosis)，具有抗癌活性。

MDM2 4-p53-IN-3，一种针对MDM2 4-p53蛋白-蛋白相互作用(PPI)的抑制剂，IC50s分别为18.5 nM（MDM2-p53）与14.8 nM（MDM4-p53）。该化合物主要应用于癌症研究领域，特别是结肠癌的研究。

MEL24为Mdm2 E3连接酶抑制剂，通过p53依赖机制降低细胞存活率，增强对DNA损伤剂的敏感性，适用于体外抗肿瘤研究。

MDMX MDM2-IN-2 是一款p53-MDM2 MDMX双重抑制剂，具有高效性，其对MDM2和MDMX的Ki值分别为0.23 μM和2.45 μM。该化合物阻断p53与MDM2蛋白的相互作用，从而恢复p53功能，诱导细胞周期停滞与细胞凋亡。同时，MDMX MDM2-IN-2抑制细胞迁移和侵袭，显示出潜在的抗肿瘤活性。

MDM2 XIAP-IN-2为MDM2（murine double minute 2）和XIAP（x-linked inhibitor of apoptosis protein）的双重抑制剂, 能够降解MDM2并抑制XIAP mRNA的翻译，进而抑制癌细胞生长。该化合物在针对急性淋巴细胞白血病细胞系EU-1的研究中显示出优秀的抑制效果，IC50值为0.3 μM。

MDM2 XIAP-IN-3（化合物 3e）为MDM2 XIAP双重抑制剂，能够下调MDM2与XIAP蛋白水平，提升p53表达，进而抑制癌细胞增殖并诱导细胞凋亡。

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。