An important mediator of growth arrest, senescence, and apoptosis in response to a wide range of cellular damage is the tumor suppressor protein p53. In healthy cells, the short-lived protein p53 is kept at very low levels that are frequently undetectable. When under stress, the p53 protein builds up in the cell, binds to p53-response elements in its tetrameric form, and triggers the transcription of a number of genes.
P53 causes MDM-2 to become transcriptionally active, and MDM-2 then inhibits p53 activity in a number of ways. MDM-2 inhibits p53-mediated transactivation by attaching to the p53 transactivation domain. After binding to p53, MDM-2 induces nuclear export because it has a signal sequence that is similar to the nuclear export signal of several viral proteins. Because p53 is a transcription factor, MDM-2's transport of it to the cytoplasm prevents it from accessing the DNA, which is necessary for its function. Finally, because MDM-2 is an ubiquitin ligase, it can direct the proteasome to target p53 for destruction.
The overexpression of the negative regulators MDM2 and MDM4 or the diminished activity of the MDM2 inhibitor ARF both inactivate p53 in many tumors. In these tumors, small molecules that block the interaction of MDM2 and/or MDM4 with p53 can cause the pathway to be reactivated. Trials on such molecules are currently being conducted.
| Structure | Cat No. | Product Name | CAS No. | Product Description |
|---|---|---|---|---|
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V3661 | RO8994 | 1309684-94-3 | RO8994, a spiroindolinone-based compound, is a novel, highly potent and selective small-molecule inhibitor of p53/MDM2 interaction with IC50 of 5 nM in a HTRF binding assay and 20 nM in a MTT proliferation assay. |
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V4660 | Siremadlin | 1448867-41-1 | Siremadlin (formerly also known as NVP-HDM201;NVP-HDM-201; HDM-201; HDM201) is a novel,potent, highly specific and orally bioavailable MDM-2/p53inhibitor with potential antitumor activity. |
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V15085 | SP-141 | 1253491-42-7 | SP-141 is a novel, cell-permeable, selective and high affinity MDM2 inhibitor (Ki = 28 nM) with excellent in-vitro and in-vivo anticancer activity. |
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V51379 | Sulanemadlin (ALRN-6924; MP-4897) | 1451199-98-6 | PPI inhibitor; p53-MDM2 |
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V0044 | YH239-EE | 1364488-67-4 | YH239-EE (YH239-EE; YH239EE; YH239 EE), the ethyl ester of YH239, is a novel and highly potent antagonist of p53/MDM2 (murine double minute 2) protein protein interaction. |
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