SCH529074

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

SCH529074 

SCH529074 是一种具有口服活性的 p53 激活剂。SCH529074 与 p53 DBD 特异性结合并与构象相关，其 Ki 值为 1-2 μM。SCH529074 恢复突变的 p53 功能，并阻断 HDM2 介导的野生型 p53 泛素化。SCH529074 可用于非小细胞肺癌 NSCLC 的研究。

SCH529074

SCH529074 Chemical Structure

CAS No. : 922150-11-6

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生物活性

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].

IC50 & Target

Ki: 1-2 μM (p53 DBD)[2]
体外研究
(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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

体内研究
(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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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

分子量

563.56

Formula

C31H36Cl2N6
CAS 号

922150-11-6
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
溶解性数据
In Vivo:
  • 1.

    It is in 20% hydroxylpropyl-β-cyclodextran as well as vehicle[2]
参考文献

  • [1]. Miljana Nenkov, et al. Growth Inhibitory Role of the p53 Activator SCH 529074 in non‑small Cell Lung Cancer Cells Expressing Mutant p53. Oncol Rep. 2020 Jun;43(6):2073-2082.

    [2]. Mark Demma, et al. 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 Biol Chem. 2010 Apr 2;285(14):10198-212.

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