VPC-70619
目录号 : GC64562VPC-70619 是一种有效的口服活性 N-Myc 抑制剂。VPC-70619 阻止 N-Myc-Max 杂复合物与 DNA E-box 结合,并表现出对 N-Myc 依赖性细胞系的强抑制活性以及口服和腹腔内给药的高生物利用度。
Cas No.:2361742-30-3
Sample solution is provided at 25 µL, 10mM.
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VPC-70619 is a potent, orally active N-Myc inhibitor. VPC-70619 blocks the N-Myc-Max heterocomplex from binding to DNA E-boxes and demonstrated strong inhibition activity against N-Myc-dependent cell lines as well as high bioavailability in both oral and intraperitoneal administration[1].
[1]. Ton AT, et al. Development of VPC-70619, a Small-Molecule N-Myc Inhibitor as a Potential Therapy for Neuroendocrine Prostate Cancer. Int J Mol Sci. 2022;23(5):2588. Published 2022 Feb 26.
Cas No. | 2361742-30-3 | SDF | Download SDF |
分子式 | C16H8ClF3N4O | 分子量 | 364.71 |
溶解度 | 储存条件 | Store at -20°C | |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.7419 mL | 13.7095 mL | 27.419 mL |
5 mM | 0.5484 mL | 2.7419 mL | 5.4838 mL |
10 mM | 0.2742 mL | 1.371 mL | 2.7419 mL |
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Development of VPC-70619, a Small-Molecule N-Myc Inhibitor as a Potential Therapy for Neuroendocrine Prostate Cancer
Int J Mol Sci 2022 Feb 26;23(5):2588.PMID:35269731DOI:10.3390/ijms23052588.
The Myc family of transcription factors are involved in the development and progression of numerous cancers, including prostate cancer (PCa). Under the pressure of androgen receptor (AR)-directed therapies resistance can occur, leading to the lethal form of PCa known as neuroendocrine prostate cancer (NEPC), characterized among other features by N-Myc overexpression. There are no clinically approved treatments for NEPC, translating into poor patient prognosis and survival. Therefore, there is a pressing need to develop novel therapeutic avenues to treat NEPC patients. In this study, we investigate the N-Myc-Max DNA binding domain (DBD) as a potential target for small molecule inhibitors and utilize computer-aided drug design (CADD) approaches to discover prospective hits. Through further exploration and optimization, a compound, VPC-70619, was identified with notable anti-N-Myc potency and strong antiproliferative activity against numerous N-Myc expressing cell lines, including those representing NEPC.
GSK2801 Reverses Paclitaxel Resistance in Anaplastic Thyroid Cancer Cell Lines through MYCN Downregulation
Int J Mol Sci 2023 Mar 22;24(6):5993.PMID:36983070DOI:10.3390/ijms24065993.
Anaplastic thyroid cancer (ATC) is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. Treatment with taxanes (such as paclitaxel) is an important approach in counteracting ATC or slowing its progression in tumors without known genetic aberrations or those which are unresponsive to other treatments. Unfortunately, resistance often develops and, for this reason, new therapies that overcome taxane resistance are needed. In this study, effects of inhibition of several bromodomain proteins in paclitaxel-resistant ATC cell lines were investigated. GSK2801, a specific inhibitor of BAZ2A, BAZ2B and BRD9, was effective in resensitizing cells to paclitaxel. In fact, when used in combination with paclitaxel, it was able to reduce cell viability, block the ability to form colonies in an anchor-independent manner, and strongly decrease cell motility. After RNA-seq following treatment with GSK2801, we focused our attention on MYCN. Based on the hypothesis that MYCN was a major downstream player in the biological effects of GSK2801, we tested a specific inhibitor, VPC-70619, which showed effective biological effects when used in association with paclitaxel. This suggests that the functional deficiency of MYCN determines a partial resensitization of the cells examined and, ultimately, that a substantial part of the effect of GSK2801 results from inhibition of MYCN expression.