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
3431 BTSA1 Potent activator of proapoptotic BAX €110.00
2025 CC-401 ATP-competitive JNK inhibitor €115.00
2634 CC-930 Potent, selective, and orally active anti-fibrotic JNK inhibitor €95.00
3228 CDK inhibitor CR8 Potent CDK inhibitor (1, 2, 5, 7, and 9 specific) €130.00
1636 CHIR 124 CHK1 inhibitor €60.00
2841 COTI-2 Reactivator of mutant p53 €125.00
1495 CP 466722 ATM inhibitor €70.00
2173 CX 5461 Inhibitor of RNA Polymerase I (RNAP1) €120.00
1534 Dapivirine NNRT inhibitor €80.00
1815 Delavirdine NNRT inhibitor (HIV-1) €90.00
1643 HLI 373 HDM2 inhibitor €95.00
1538 JNJ 26854165 HDM2 inhibitor €105.00
1586 JNJ 26854165 dihydrochloride HDM2 inhibitor €105.00
2949 JNK inhibitor VIII Selective, ATP-competitive, and cell-permeable JNK inhibitor €105.00
2361 JNK-IN-8 Remarkably potent and selective covalent inhibitor of JNK €95.00

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