1. Apoptosis
  2. MDM-2/p53

MDM-2/p53

The p53 tumor suppressor is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage. p53 is a short-lived protein that is maintained at low, often undetectable, levels in normal cells. Under stress conditions, the p53 protein accumulates in the cell, binds in its tetrameric form to p53-response elements and induces the transcription of various genes.

MDM-2 is transcriptionally activated by p53 and MDM-2, in turn, inhibits p53 activity in several ways. MDM-2 binds to the p53 transactivation domain and thereby inhibits p53-mediated transactivation. MDM-2 also contains a signal sequence that is similar to the nuclear export signal of various viral proteins and, after binding to p53, it induces its nuclear export. As p53 is a transcription factor, it needs to be in the nucleus to be able to access the DNA; its transport to the cytoplasm by MDM-2 prevents this. Finally, MDM-2 is a ubiquitin ligase, so is able to target p53 for degradation by the proteasome.

In many tumors p53 is inactivated by the overexpression of the negative regulators MDM2 and MDM4 or by the loss of activity of the MDM2 inhibitor ARF. The pathway can be reactivated in these tumors by small molecules that inhibit the interaction of MDM2 and/or MDM4 with p53. Such molecules are now in clinical trials.

MDM-2/p53 Related Products (48):

Cat. No. Product Name Effect Purity
  • HY-15484
    Pifithrin-α hydrobromide p53 Inhibitor 98.28%
    Pifithrin-α hydrobromide is an inhibitor of p53, also acts as an aryl hydrocarbon receptor (AhR) agonist.
  • HY-15676
    RG7388 MDM2 Inhibitor 99.97%
    RG7388 is a potent and selective MDM2 antagonist, inhibiting p53-MDM2 binding, with IC50 of 6 nM.
  • HY-32735
    Triptolide MDM2 Inhibitor 99.83%
    Triptolide is an inhibitor of heat shock factor (HSF1), inhibits HSP90-CDC37 binding and induces acetylation of HSP90, and also inhibits MDM2 expression in a dose-dependent manner with IC50 values range from 47 to 73 nM.
  • HY-10029
    Nutlin 3a MDM2 Inhibitor 98.11%
    Nutlin 3a is an active enantiomer of Nutlin-3, acts as a murine double minute (MDM2) antagonist that inhibits MDM2-p53 interactions and stabilizes the p53 protein, and thereby induces cell cycle arrest and apoptosis.
  • HY-12296
    AMG 232 MDM2 Inhibitor 99.73%
    AMG 232 is an extremely potent, selective and orally available inhibitor of p53-MDM2 interaction, with an IC50 of 0.6 nM, and binds to MDM2 with a Kd of 0.045 nM.
  • HY-101266
    Milademetan MDM2 Inhibitor
    Mliademetan is a specific MDM2 inhibitor, a pharmaceutical composition for use in treating acute myeloid leukemia (AML).
  • HY-12734
    AM-8735 MDM2 Inhibitor
    AM-8735 is a potent and selective MDM2 inhibitor with an IC50 of 25 nM.
  • HY-50696
    Nutlin 3 MDM2 Inhibitor 98.32%
    Nutlin 3 is a commercial available p53-MDM2 inhibitor, with Ki of 90 nM.
  • HY-10959
    RG7112 MDM2 Inhibitor 99.94%
    RG7112 is the first clinical and orally available MDM-2/p53 inhibitor designed to occupy the p53-binding pocket of MDM2, with the Kd value of 11 nM.
  • HY-15695
    Puromycin aminonucleoside p53 Activator 98.31%
    Puromycin aminonucleoside is the aminonucleoside portion of the antibiotic puromycin, and a puromycin analog which does not inhibit protein synthesis or induce apoptosis.
  • HY-16702A
    Pifithrin-β hydrobromide p53 Inhibitor 99.90%
    Pifithrin-β is a potent p53 inhibitor with an IC50 of 23 μM.
  • HY-18986
    SAR405838 MDM2 Inhibitor 98.95%
    SAR405838 is a highly potent and selective MDM2 inhibitor, binds to MDM2 with Ki= 0.88 nM and has high specificity over other proteins.
  • HY-15954
    NVP-CGM097 MDM2 Inhibitor 98.32%
    NVP-CGM097 is a potent and selective MDM2 inhibitor with IC50 of 1.7±0.1 nM for hMDM2.
  • HY-13424
    RITA p53 Activator
    RITA is an inhibitor of p53-HDM-2 interaction, binds to p53dN, with a Kd of 1.5 nM, and also induces DNA-DNA cross-links.
  • HY-19980
    PRIMA-1Met p53 Activator >99.0%
    PRIMA-1MET restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1MET also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.
  • HY-P0121
    ReACp53 p53 Activator 99.65%
    ReACp53 could inhibit p53 amyloid formation and rescue p53 function in cancer cell lines. Sequence: H-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Pro-Ile-Leu-Thr-Arg-Ile-Thr-Leu-Glu-OH.
  • HY-18658
    NVP-HDM201 MDM2 Inhibitor 99.19%
    NVP-HDM201 (HDM201) is a potent and highly specific MDM-2/p53 inhibitor currently under phase I clinical trial.
  • HY-17493
    MI-773 MDM2 Inhibitor >98.0%
    MI-773 is a new small molecule inhibitor of the MDM2-p53 interaction, binds to MDM2 with high affinity (Ki=0.88 nM) and blocks the p53-MDM2 interaction.
  • HY-19980A
    PRIMA-1 p53 Activator >98.0%
    PRIMA-1 is a mutant p53 reactivator, restores the sensitivity of TP53 mutant-type thyroid cancer cells to the histone methylation inhibitor 3-Deazaneplanocin A.
  • HY-15510B
    Tenovin 6 Hydrochloride p53 Activator >98.0%
    Tenovin-6 Hydrochloride is a water soluble inhibitor of SIRT1 and SIRT2, slightly inhibits HDAC8, and is also a potent activator of p53, with IC50s of 21 μM, 10 μM, 67 μM for SirT1, SirT2, and SirT3, respectively.