p53-Tumor Suppression

The vast majority of p53-regulated genes are induced in response to various stress signals and are responsible for maintaining genetic stability, DNArepair, regulation of crucial cell-cycle check points, and finally induction of apoptosis. The activity of p53 is tightly controlled by two major negative regulators including murine double minute 2 (MDM2; EC 6.3.2.19) and 4 (MDM4 or MDMX) proteins. Human MDM2 and MDMX are structurally related and contain three well-conserved domains: an N-terminal domain (responsible for p53 binding), a zinc-finger domain (function largely unknown) and a C-terminal RING domain (responsible for formation of homo- and heterodimers). Additionally, the RING domain of MDM2 confers E3 ubiquitin ligase activity. Concentration/activity of p53 is kept at low level in unstressed cells. This is accomplished by three parallel mechanisms mediated by MDM2 and/or MDMX. First, MDM2 and MDMX bind the N-terminal transactivation domain (TAD) of p53, preventing thereby its interaction with the transcription machinery and resulting in the inhibition of p53-responsive gene expression. Second, MDM2/X proteins export p53 outside the nucleus into the cytoplasm where it can no longer activate transcription. Finally, MDM2 marks p53 for proteasomal degradation[1]. Many tumors overproduce MDM2 to impair p53 function. Therefore, restoration of p53 activity by inhibiting the p53–MDM2 binding represents an attractive novel approach to cancer therapy[2].


[1] K. Zak et al. Mdm2 and MdmX inhibitors for the treatment of cancer: a patent review (2011 – present). Exp. Opin. Ther. Pat. 2013, 23, 425-448.
[2] B.T. Vu, L. Vassilev. Small-Molecule Inhibitors of the p53-MDM2 Interaction. Curr. Top. Microbiol. Immun. 2011, 348, 151-172.

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Axon ID Name Description From price
1505 PD 0332991 hydrochloride CDK4 and CDK6 inhibitor €85.00
1660 PF 02341066 c-MET Inhibitor; NPM-ALK inhibitor €80.00
1379 PF 477736 CHK1 inhibitor €70.00
2488 Piperlongumine Natural alkaloid with potent cytotoxic activity €65.00
1983 R 547 CDK inhibitor (1, 2, and 4 specific) €95.00
2009 RITA Activates p53 through inhibition of MDM2 €105.00
1530 RO 3306 CDK1 inhibitor €80.00
2741 SAR405838 MDM2-p53 inhibitor €125.00
1776 SCH 727965 CDK inhibitor (1, 2, 5, and 9 specific) €90.00
2186 SF 1670 Inhibitor of PTEN with significant inhibitory effect on PTPRC and GALK €120.00
2487 Silibinin Natural flavonolignan, cytoprotectant, antioxidant, and antihepatotoxic agent €40.00
2453 SirReal 2 SIRT2 inhibitor with >1000 fold selectivity over SIRT1 and SIRT3 €95.00
2164 SJ 172550 Small molecule inhibitor of MDMX €95.00
1614 SNS 032 CDK inhibitor (2, 7 and 9 specific) €85.00
2437 SP 141 Specific MDM2 inhibitor with therapeutic effects in breast cancer models €120.00

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