P53R3

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.

Product information

CAS Number: 922150-12-7

Molecular Weight: 592.56

Formula: C32H35Cl2N5O2

Chemical Name: methyl (2S)-2-{[2-({4-[bis(4-chlorophenyl)methyl]piperazin-1-yl}methyl)quinazolin-4-yl]amino}-3-methylbutanoate

Smiles: CC(C)[C@H](NC1=NC(CN2CCN(CC2)C(C2=CC=C(Cl)C=C2)C2=CC=C(Cl)C=C2)=NC2=CC=CC=C12)C(=O)OC

InChiKey: DFBRKGUTHGRQMH-LJAQVGFWSA-N

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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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. 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. 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). 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.

Products are for research use only. Not for human use.