P53R3

• CAT Number: I045523
• CAS Number: 922150-12-7
• Molecular Formula: C32H35Cl2N5O2
• Molecular Weight: 592.56
• Purity: ≥95%
• Synonyms: methyl (2S)-2-[[2-[[4-[bis(4-chlorophenyl)methyl]piperazin-1-yl]methyl]quinazolin-4-yl]amino]-3-methylbutanoate
• InChI: InChI=1S/C32H35Cl2N5O2/c1-21(2)29(32(40)41-3)37-31-26-6-4-5-7-27(26)35-28(36-31)20-38-16-18-39(19-17-38)30(22-8-12-24(33)13-9-22)23-10-14-25(34)15-11-23/h4-15,21,29-30H,16-20H2,1-3H3,(H,35,36,37)/t29-/m0/s1
• InChIKey: DFBRKGUTHGRQMH-LJAQVGFWSA-N
• SMILES: CC(C)C(C(=O)OC)NC1=NC(=NC2=CC=CC=C21)CN3CCN(CC3)C(C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl

P53R3 is a potent p53 reactivator and restores sequence-specific DNA binding of p53 hot spot mutants, including p53R175H, p53R248W and p53R273H. P53R3 induces p53-dependent antiproliferative effects with much higher specificity than PRIMA-1. P53R3 enhances the recruitment of wild-type p53 and p53M237I to several target gene promoters. P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5). P53R3 is used for cancer research[1].
P53R3 (10 μg/ml; 24 hours; in the absence or presence of the unlabelled p53 consensus oligonucleotide) restores p53-specific DNA binding activity to p53R273H (a DNA contact mutant) and p53R175H (a structural mutant) in WiDr colon tumour cells harbouring p53R273H and KLE cells with p53R175H[1].P53R3 (1-33 μg/ml; 24 hours) inhibits the proliferation of the LN-308 sublines expressing mutant p53 plasmids in a p53-dependent manner. The p53R175H-dependent effects are strong over a broad range of concentrations, but p53R273H-dependent effects are weaker and requires high concentrations of P53R3[1].P53R3 induces p53R248W reactivation is more pronounced proliferation inhibition than observed with p53R273H. P53R3 does not exhibit cytotoxic effects even at concentrations close to its solubility limit (33 μg/ml)[1].P53R3 (33 μg/ml; 18 hours) induces a strong decrease in S phase cells and a G0/G1 cell cycle arrest in LN-308 p53R175H and LN-308 p53R273H cells. But it does not affect cell cycle distribution of LN-308 p53R248W cells[1].

Reference

[1]. Alejandro Parrales, et al. Targeting Oncogenic Mutant p53 for Cancer Therapy. Front Oncol
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