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 (63):

Cat. No. Product Name Effect Purity
  • HY-15676
    Idasanutlin MDM2 Inhibitor 99.90%
    Idasanutlin (RG7388) is a potent and selective MDM2 antagonist, inhibiting p53-MDM2 binding, with an IC50 of 6 nM.
  • HY-10029
    Nutlin-3a MDM2 Inhibitor 98.07%
    Nutlin-3a, an active enantiomer of Nutlin-3, is a potent murine double minute (MDM2) inhibitor (IC50=90 nM). Nutlin-3a inhibits MDM2-p53 interactions and stabilizes the p53 protein, and induces cell autophagy and apoptosis. Nutlin-3a has the potential for the study of TP53 wild-type ovarian carcinomas[1][2].
  • HY-12296
    AMG 232 MDM2 Inhibitor 99.90%
    AMG 232 is a potent, selective and orally available inhibitor of p53-MDM2 interaction, with an IC50 of 0.6 nM. AMG 232 binds to MDM2 with a Kd of 0.045 nM.
  • HY-15484
    Pifithrin-α hydrobromide p53 Inhibitor
    Pifithrin-α hydrobromide is a p53 inhibitor which blocks its transcriptional activity and prevents cells from apoptosis. Pifithrin-α hydrobromide is also an aryl hydrocarbon receptor (AhR) agonist.
  • 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-W011434
    Triglycidyl isocyanurate p53 Activator
    Triglycidyl isocyanurate (TGIC; Teroxirone) is a triazene triepoxide with antiangiogenic and antineoplastic activities. Triglycidyl isocyanurate inhibits the growth of non-small-cell-lung cancer cells via p53 activation. Triglycidyl isocyanurate induces cell apoptosis. Triglycidyl isocyanurate can be used for cancer research[1][2].
  • HY-B0639A
    Amifostine trihydrate p53 Activator
    Amifostine trihydrate (WR2721 trihydrate) is a broad-spectrum cytoprotective agent and a radioprotector. Amifostine trihydrate selectively protects normal tissues from damage caused by radiation and chemotherapy. Amifostine trihydrate is potent hypoxia-inducible factor-α1 (HIF-α1) and p53 inducer. Amifostine trihydrate protects cells from damage by scavenging oxygen-derived free radicals. Amifostine trihydrate reduces renal toxicity and has antiangiogenic action[1][2][3][4].
  • HY-130684
    MDM2-IN-1 MDM2 Inhibitor
    MDM2-IN-1 (Compound 30) is a synthetic MDM2-p53 interaction (MDM2) inhibitor and contains the trans (D-)configuration[1].
  • HY-50696
    Nutlin-3 MDM2 Inhibitor 98.32%
    Nutlin-3 is a commercial available p53-MDM2 inhibitor, with Ki of 90 nM.
  • HY-16702A
    Pifithrin-β hydrobromide p53 Inhibitor 99.93%
    Pifithrin-β hydrobromide (PFT β hydrobromide) is a potent p53 inhibitor with an IC50 of 23 μM.
  • HY-10959
    RG7112 MDM2 Inhibitor 99.91%
    RG7112 is a potent, selective, first clinical, orally active and blood-brain barrier crossed MDM2-p53 inhibitor, with an IC50 of 18 nM and a KD of 11 nM for binding to MDM2[1].
  • HY-18658
    Siremadlin MDM2 Inhibitor 99.19%
    Siremadlin (NVP-HDM201) is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor.
  • HY-B0639
    Amifostine p53 Activator >98.0%
    Amifostine (WR2721) is a broad-spectrum cytoprotective agent and a radioprotector. Amifostine selectively protects normal tissues from damage caused by radiation and chemotherapy. Amifostine is potent hypoxia-inducible factor-α1 (HIF-α1) and p53 inducer. Amifostine protects cells from damage by scavenging oxygen-derived free radicals. Amifostine reduces renal toxicity and has antiangiogenic action[1][2][3][4].
  • HY-10940
    Pifithrin-μ p53 Inhibitor 98.31%
    Pifithrin-μ is an inhibitor of p53 and HSP70, with antitumor and neuroprotective activity.
  • HY-13424
    RITA p53 Activator 99.57%
    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-18935A
    CBL0137 hydrochloride p53 Activator 98.25%
    CBL0137 hydrochloride is an inhibitor of the histone chaperone, FACT. CBL0137 hydrochloride can also activate p53 and inhibits NF-κB with EC50s of 0.37 and 0.47 µM, respectively.
  • HY-17493
    MI-773 MDM2 Inhibitor 98.05%
    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-15510
    Tenovin-6 p53 Activator 98.61%
    Tenovin-6, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC50s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH)[1][2].
  • HY-18986
    SAR405838 MDM2 Inhibitor
    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-114312
    MD-224 MDM2 Inhibitor 99.74%
    MD-224 is a first-in-class and highly potent small-molecule human murine double minute 2 (MDM2) degrader based on the proteolysistargeting chimera (PROTAC) concept. MD-224 induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells, and achieves an IC50 value of 1.5 nM in inhibition of growth of RS4;11 cells. MD-224 has the potential to be a new class of anticancer agent[1].