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.
|Anticancer agent 68
|CBL0137 HCl, the hydrochloride salt of CBL-0137 (formerly Curaxin 137 or CBL 0137), is an inhibitor of the histone chaperone,FACT (facilitates chromatin transcription complex).
|COTI-2 is an orally available, 3rd generation small molecule activator of the mutant p53 protein (a tumor suppressor).
|Ivaltinostat formic (CG-200745 formic)
|Serdemetan (formerly JNJ26854165; JNJ-26854165; JNJ 26854165), originally developed as an activator of p53, is now considered to be a novel, potent and orally bioactive antagonist of Human Double Minute-2 (HDM-2) ubiquitin ligase with antitumor activities.
|Kevetrinhydrochloride (also known as thioureidobutyronitrile; 4-Isothioureidobutyronitrile hydrochloride; thioureidobutyronitrile hydrochloride; thioureido butyronitrile hydrochloride), is a water-soluble, small molecule activator of the tumor suppressor protein p53.
|MI-773 (2'S,3R isomer, SAR-405838)
|MI-773 (2S,3R isomer, SAR405838) is a novel, potent, specific and orally bioavailable small molecule antagonist of MDM2/piro-oxindole HDM2 (Murine double minute 2/human double minute 2) with a Ki value of 0.88 nM.
|MS7972 is a novel and potent CREBBP inhibitor.
|NSC 146109 HCl
|NSC 146109 (NSC-146109) HCl, the hydrochloride salt ofNSC-146109, is a novel and potent small-molecule p53 activator that targets MDMX, it has the potential in treating breast cancer.
|NSC319726 is a novel and potent p53(R175) mutant reactivator with with potential anticancer activity.
|NSC59984 is a novel and potent activator of p53 with potential anticancer activity.
|p53 (17-26), FITC labeled
|Pifithrin-α (PFTα) HBr
|Pifithrin-α HBr ((PFTα hydrobromide; PFT-α) is a novel and potent inhibitor of p53, acting by inhibiting p53 protein transcription and p53-dependent transactivation of p53-responsive genes.