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.

Items 1 to 15 of 60 total

per page
Page:
  1. 1
  2. 2
  3. 3
  4. 4
Axon ID Name Description From price
1291 AEG 3482 JNK inhibitor €85.00
2269 AK 1 Potent inhibitor of SIRT with good selectivity for SIRT2 over SIRT1 and SIRT3 €90.00
2270 AK 7 Potent, brain-permeable and selective inhibitor of SIRT2 €90.00
2639 AMG 232 Potent, selective, and orally bioavailable MDM2-p53 inhibitor €115.00
2002 AS 602801 JNK inhibitor, which inhibited JNK1, JNK2 and JNK3 €120.00
1539 AT 7519 mesylate CDK inhibitor €85.00
5051 Axon Ligands™ Cell signaling and Oncology compound library Axon Ligands™ Cell signaling and Oncology compound library Inquire
2345 AZ 20 Potent, orally active and selective inhibitor of ATR protein kinase €105.00
1966 AZD 5438 CDK inhibitor (1, 2, and 9 specific) €80.00
1399 AZD 7762 hydrochloride CHK inhibitor €60.00
2185 BAM 7 Selective small-molecule activator of proapoptotic BAX €105.00
2301 BIBR 1532 Potent and selective telomerase inhibitor inducing senescence in human cancer cells. €70.00
2462 BMH 21 Inhibitor of RNA Polymerase I (RNAP1) €95.00
2025 CC 401 ATP-competitive JNK inhibitor €145.00
2634 CC-930 Potent, selective, and orally active anti-fibrotic JNK inhibitor €105.00

Items 1 to 15 of 60 total

per page
Page:
  1. 1
  2. 2
  3. 3
  4. 4
Please wait...