| Identification | Back Directory | [Name]
SCH 529074 | [CAS]
922150-11-6 | [Synonyms]
SCH 529074
N3-[2-[[4-[Bis(4-chlorophenyl)methyl]-1-piperazinyl]methyl]-4-quinazolinyl]-N1,N1-dimethyl-1,3-propanediamine | [Molecular Formula]
C31H36Cl2N6 | [MDL Number]
MFCD27937757 | [MOL File]
922150-11-6.mol | [Molecular Weight]
563.56 |
| Chemical Properties | Back Directory | [Boiling point ]
640.3±55.0 °C(Predicted) | [density ]
1.262±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 33 mg/ml; DMSO: 25 mg/ml; Ethanol: 33 mg/ml | [form ]
A crystalline solid | [pka]
9.44±0.28(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Description]
SCH 529074 is a small molecule activator of p53, a tumor suppressor that is mutated or non-functional in 50% of human tumors. SCH 529074 restores DNA binding activity and increases DNA binding affinity of two recombinant GST fusion mutant p53 DNA binding domains (R273H and R249S) in an electrophoretic mobility shift assay with Kd values of 0.6740 and 0.4313, respectively. It also stimulates DNA binding activity and prevents human double minute-2 (Hdm-2) ubiquitination of wild-type p53 in vitro. SCH 29074 reduces proliferation of tumor cell lines with mutant and wild-type p53 (EC50s = 400-3,700 nM), with the p53 mutant cell lines being the most sensitive. In vivo, SCH 529074 reduces tumor growth in a DLD-1 human colorectal cancer xenograft model in mice in a dose-dependent manner. | [Uses]
SCH 529074 is a small molecule activator of mutant p53, which binds p53 DNA binding domain (DBD), restores growth-suppressive function to mutant p53 and interrupts HDM2-mediated ubiquination of wild type p53. | [in vivo]
SCH529074 (oral administration; 30 or 50 mg/kg; twice daily; 4 weeks; started on day 3 until day 31) causes 79 and 43% reduction of tumor growth at 50 and 30 mg/kg doses, respectively. the degree of tumor inhibition correlates with the plasma exposure of the compound (0.26–0.55 μm?at 30 mg/kg and 0.39-0.79 μm?at 50 mg/kg, 2-12 h post final dosing) in human DLD-1 colorectal cancer xenograft[2]. | Animal Model: | Female nude mice, 5–7 weeks of age, received subcutaneous inoculation of DLD-1 human colorectal carcinoma cells[2] | | Dosage: | 30 or 50 mg/kg | | Administration: | Oral administration; twice daily; 4 weeks; started on day 3 until day 31 | | Result: | Inhibited tumor growth |
| [References]
[1] MARK DEMMA. SCH529074, a small molecule activator of mutant p53, which binds p53 DNA binding domain (DBD), restores growth-suppressive function to mutant p53 and interrupts HDM2-mediated ubiquitination of wild type p53.[J]. The Journal of Biological Chemistry, 2010: 10198-10212. DOI: 10.1074/jbc.m109.083469 |
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