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), an inhibitor of the p53-MDM2 X protein interaction, exhibits a K i value of 23.35 µM and holds potential for applications in anti-tumor research.

MDM2 XIAP-IN-1 (compound 14) is an orally active dual inhibitor of MDM2 and XIAP, displaying anti-cancer activity with an IC50 of 0.3 μM and potential applications in cancer research [1].

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, capable of recruiting E3 ligases like VHL, CRBN, MDM2, and IAP. It is utilized in synthesizing PROTAC K-Ras Degrader-1, 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 comprising a ligand for the K-Ras recruiting moiety and a PROTAC linker, responsible for recruiting E3 ligases (e.g., VHL, CRBN, MDM2, and IAP). This compound is essential for synthesizing PROTAC K-Ras Degrader-1, a potent degrader with a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 4 is a chemical compound combining a K-Ras recruiting ligand with a PROTAC linker, responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. It has the potential to be used in synthesizing PROTAC K-Ras Degrader-1, which shows a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 5 is a chemical compound combining a K-Ras recruiting ligand with a PROTAC linker for E3 ligases, such as VHL, CRBN, MDM2, and IAP. This conjugate is crucial for synthesizing PROTAC K-Ras Degrader-1, displaying a degradation efficacy of ≥70% in SW1573 cells [1].

HL001 is an orally active small molecule inhibitor of cyclophilin A (CypA) and a receptor antagonist of lysophosphatidic acid 1 (LPA1). It induces cell cycle arrest and apoptosis in tumor cells via p53. By downregulating G3BP1, HL001 promotes reactive oxygen species production and DNA damage to stabilize p53. It disrupts the interaction between MDM2 and p53-72R in a CypA-dependent manner. HL001 exhibits antitumor activity and can also be used in research on pulmonary fibrosis.

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 is a Thalidomide analogue. BTX161 is a potent CKIα degrader. In human AML cells, BTX161 mediates the CKIα degradation better than Lenalidomide as well as activates DNA damage response (DDR) and p53, and also stabilizes the p53 antagonist MDM2[1].

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, an orally active and specific MDM2 inhibitor, is utilized in the study of acute myeloid leukemia (AML) and solid tumors. It induces G1 cell cycle arrest, senescence, and apoptosis, showcasing its therapeutic potential [1] [2].

MI-1061 TFA, a potent and orally bioavailable MDM2 inhibitor (MDM2-p53 interaction), demonstrates significant chemical stability with an IC 50 of 4.4 nM and a K i of 0.16 nM. It effectively activates p53 and induces apoptosis within SJSA-1 xenograft tumor tissues in mice, showcasing notable anti-tumor activity [1].

MDM2 4-p53-IN-2 (2q) is a potent dual inhibitor of MDM2 MDM4 and activator of p53, demonstrating IC50 values of 70.7 nM for MDM2-p53 and 81.4 nM for MDM4-p53 complexes. It facilitates cell cycle regulation, promotes apoptosis, and exhibits anticancer properties [1].

MDM2 4-p53-IN-3, an inhibitor of MDM2 4-p53 protein-protein interactions (PPIs), exhibits potent activity with IC50 values of 18.5 nM for MDM2-p53 and 14.8 nM for MDM4-p53. This compound is applicable in cancer research, including studies on colon cancer [1].

MEL24, an Mdm2 E3 ligase inhibitor, diminishes cell viability and enhances sensitivity to DNA-damaging agents in a p53-dependent manner, suggesting its potential for in vitro antitumor research [1].

MDMX MDM2-IN-2 is a potent dual inhibitor of p53-MDM2 MDMX, with dissociation constants (Kis) of 0.23 μM for MDM2 and 2.45 μM for MDMX. It disrupts the interaction between p53 and MDM2 proteins, reinstating p53 functionality to induce cell cycle arrest and apoptosis. Additionally, this compound impedes cell migration and invasion, exhibiting notable antitumor activity [1].

MDM2 XIAP-IN-2 is a dual inhibitor targeting murine double minute 2 (MDM2) and X-linked inhibitor of apoptosis protein (XIAP), promoting MDM2 degradation and impeding XIAP mRNA translation, thereby inhibiting cancer cell proliferation. It exhibits potent activity against the acute lymphoblastic leukemia cell line EU-1, with an IC50 of 0.3 μM [1].

MDM2 XIAP-IN-3 (compound 3e), a dual inhibitor of MDM2 and XIAP, reduces MDM2 and XIAP protein levels while increasing p53 expression, ultimately inhibiting cancer cell proliferation and inducing apoptosis [1].