p53-mdmx

RO-5963 is a dual inhibitor of p53-MDM2 and p53-MDMX (IC50s: ~17 nM and ~24 nM, respectively).

NSC 146109 hydrochloride is an activator of p53 targeting MDMX. NSC 146109 hydrochloride can be used for studies on breast cancer.

SJ-172550 is a small molecule inhibitor of MDMX (EC50: 5 μM).

MEL23 is an MDM2E3 ligase inhibitor that prevents the E3 ligase activity of the MDM2-MDMX complex. It inhibits the ubiquitination of Mdm2 and p53 in cells, reducing the viability of wild-type p53 cells. Additionally, MEL23 stabilizes MDM2 through a mechanism independent of p53 transcription.

MMRi6 is an inhibitor of the Mdm2-MdmX RING domain, capable of disrupting Mdm2-MdmX RING-RING interactions in vitro. It inhibits MdmX-stimulated Mdm2 autoubiquitination and Mdm2-MdmX-mediated polyubiquitination of p53 without affecting NEDD4-1 autoubiquitination. In wt-p53 Emu-myc lymphoma cells, MMRi6 induces p53 stabilization and accumulation, as well as PARP cleavage. It inhibits the growth of wt-p53 and p53-null Emu-myc lymphoma cells, with IC50 values of approximately 0.5 μM and 3 μM, respectively. MMRi6 is applicable in leukemia/lymphoma research.

WK-298 is an effective MDM2/MDMX-p53 interaction inhibitor.

MMRi64 is a specific inhibitor of Mdm2-MdmX E3 ligase activity.MMRi64 potently induces p53 accumulation and apoptosis in the p53 pathway in leukemia/lymphoma cells, disrupts Mdm2-MdmX interactions, and downregulates Mdm2 and MdmX in leukemia cells.MMRi64 MMRi64 can be used in cancer research.

XI-006 (XI-006) suppresses MDMX with IC50 of 2.5 μM, leading to enhanced p53 stabilization/activation and DNA damage, and also regulates MDM2, an E3 ligase.

RO2443 is a dual inhibitor of the MDM2-p53 or MDMX-p53 protein-protein interaction, inducung MDM2 and MDMX dimerization and activating the p53 pathway.

Sulanemadlin (ALRN-6924) is a potent peptidomimetic macrocycle that inhibits p53-MDM2 and p53-MDMX protein-protein interactions, serving as a valuable tool for cancer 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].

Phage-derived 12/1 peptide demonstrates antitumor activity by targeting MDM2 and MDMX, thereby disrupting the MDM2-p53 and MDMX-p53 interactions, with IC50 values of 0.15 and 1.25 μM, respectively [1].

DPMI-ω is a dual-specific D-peptide antagonist of the carcinogenic proteins MDM2 and MDMX. When loaded onto gold nanoparticles, DPMI-ω effectively penetrates tumor cells and kills them by reactivating the p53 signaling pathway. It disrupts the p53-MDM2/MDMX complex and inhibits the growth of B16 melanoma while inducing G0/G1 phase cell cycle arrest. Combined with anti-PD1 antibodies, DPMI-ω enhances immunotherapy by amplifying CD3+/CD8+ cytotoxic T cells and inhibiting CD4+/CD25+ regulatory T cells. DPMI-ω is applicable in melanoma research.