P53R3

SKU: orb1690145

Description

P53R3 is a potent small molecule reactivator of mutant p53, restoring DNA binding and transcriptional activity to common hotspot mutants like R175H, R248W, and R273H. It induces p53-dependent antiproliferation and upregulates DR5 expression, making it a valuable tool for studying p53 reactivation and apoptosis in cancer cell lines and in vivo models.

Research Area

Cell Biology

Key Properties

• CAS Number: 922150-12-7
• MW: 592.56
• Purity: 99.06% (May vary between batches)
• Formula: C₃₂H₃₅Cl₂N₅O₂
• SMILES: COC(=O)[C@@H](Nc1nc(CN2CCN(CC2)C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)nc2ccccc12)C(C)C
• Target: MDM-2/p53,p53
• Solubility: DMSO:90 mg/mL (151.88 mM)

Bioactivity

• In Vitro:
  P53R3, at a concentration of 10 μg/ml for 24 hours, reestablishes p53-specific DNA binding activity in WiDr colon tumor cells with p53 R273H and KLE cells with p53R175H, both in the absence or presence of the unlabelled p53 consensus oligonucleotide. Additionally, P53R3 displays a dose-dependent inhibition of proliferation in LN-308 sublines expressing mutant p53 plasmids, with a pronounced effect against p53 R175H across a wide concentration range (1-33 μg/ml; 24 hours), and a more selective efficacy against p53 R273H at higher doses. Notably, P53R3 induces a more significant anti-proliferative response through reactivation of p53 R248W compared to p53 R273H without exhibiting cytotoxicity up to its solubility limit (33 μg/ml). At a higher concentration of 33 μg/ml over 18 hours, P53R3 prompts a marked reduction in S phase cells and induces G0/G1 cell cycle arrest in LN-308 cells harboring p53 R175H and p53 R273H mutations, but does not affect the cell cycle distribution of LN-308 cells with p53 R248W. Through a cell viability assay on LN-308 human glioma cells carrying control, p53 R175H, p53 R248W, and p53 R273H plasmids, it induces both p53-dependent and -independent anti-proliferative and cytotoxic effects in vitro .
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

p53, P53R3, P-53R3

Compound Identifiers

PubChem CID

58809185