922150-11-6
922150-11-6 structure
- Name: SCH 529074
- Chemical Name: N1-(2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)quinazolin-4-yl)-N3,N3-dimethylpropane-1,3-diamine
- CAS Number: 922150-11-6
- Molecular Formula: C31H36Cl2N6
- Molecular Weight: 563.56400
- Catalog: Signaling Pathways Apoptosis MDM-2/p53
- Create Date: 2016-05-10 00:17:03
- Modify Date: 2024-01-11 16:43:19
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SCH529074 is a potent and orally active p53 activator. SCH529074 binds specifically and conformation-dependently to p53 DBD ( DNA binding domain) with a Ki of 1-2 μM in a saturable manner. SCH529074 restores mutant p53 function and interrupts HDM2-mediated ubiquitination of wild Type p53. SCH529074 can be used for the study of non-small-cell lung carcinoma (NSCLC)[1][2].
| Name | N1-(2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)quinazolin-4-yl)-N3,N3-dimethylpropane-1,3-diamine |
|---|---|
| Synonyms | sch 529074 |
| Description | SCH529074 is a potent and orally active p53 activator. SCH529074 binds specifically and conformation-dependently to p53 DBD ( DNA binding domain) with a Ki of 1-2 μM in a saturable manner. SCH529074 restores mutant p53 function and interrupts HDM2-mediated ubiquitination of wild Type p53. SCH529074 can be used for the study of non-small-cell lung carcinoma (NSCLC)[1][2]. |
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| Related Catalog | |
| Target |
Ki: 1-2 μM (p53 DBD)[2] |
| In Vitro | SCH529074 (2-4 µM; 24 hours) causes significant reduction in cell viability, it causes a significant decreasing to 20-25% in p53 mutant cells (H157, H1975 and H322) and to 68% in the p53 WT cell line A549 at 4 µM[1]. SCH 529074 (2 and 4 µM) induces NSCLC cells (H157, A549, HCT116 and HCT116 p53-/-) arrested at the G0/G1 phase (59%; 72%; 66%; and 57%) compared with the control cells following low concentration (2 µM) of treatment[1]. SCH 529074 (2-4 µM; 24 hours) induces the early and late apoptotic rates at 2 µM in H1975 cells. In H157 cells, SCH 529074 treatment induces early and late apoptosis. Similarly, in A549 cells, 2 and 4 µM of SCH 529074 significantly increased early and late apoptosis. In line with that, in colon cancer cells, in HCT116 cells, 4 µM of SCH 529074 causes a significant induction of early and late apoptosis, and 4 µM of SCH 529074 significantly induces early apoptosis in HCT116 p53-/- cells[1]. SCH 529074 (2-6 µM; 24 hours) increases the protein levels of PUMA and p21 revealed to 4 or 6 µM in the cancer cell lines regardless of their p53 status[1]. Cell Viability Assay[1] Cell Line: p53 mutant cells (H157, H1975 and H322) and p53 WT cell line A549 Concentration: 2 µM; 4 µM Incubation Time: 24 hours Result: Inhibited cancer WT and mutant cell viability. Cell Cycle Analysis[1] Cell Line: H1975, H157, A549, HCT116, HCT116 p53-/- cells Concentration: 2 µM, 4 µM, 6 µM Incubation Time: 24 hours Result: Induced apoptosis in all assessed NSCLC cell lines irrespective of their p53 mutational status. Western Blot Analysis[1] Cell Line: H1975, H322, H157, A549, HCT116, HCT116 p53-/- Concentration: 2 µM, 4 µM, 6 µM Incubation Time: 24 hours Result: Increased PUMA and p21 protein expression. |
| 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 |
| Molecular Formula | C31H36Cl2N6 |
|---|---|
| Molecular Weight | 563.56400 |
| Exact Mass | 562.23800 |
| PSA | 47.53000 |
| LogP | 6.15620 |