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CAS No.: 1610964-64-1

Unesbulin Catalog No. CSN24787

Synonyms: PTC596

PTC596 is an orally active and selective B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) inhibitor. PTC596 targets BMI1 expressed by both tumor cells and cancer stem cells (CSCs), and induces hyper-phosphorylation of BMI1, leading to its degradation. PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells[1][2].

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实验方案

技术信息

生物活性

描述B-cell specific Moloney murine leukemia virus integration site 1 (BMI-1) has pleiotropic function in several cellular processes, including DNA damage, apoptosis, senescence, and self-renewal of stem cells. BMI-1 also plays a central role in cancer stem cell growth and survival in various neoplasia, PTC596 is a small molecule selective inhibitor of BMI1. PTC596 can inhibited proliferation of mantle cell lymphoma (MCL) cell lines, including REC-1, NCEB-1, MINO, MAVER-1, JVM-2, Granta-519, Jeko-1, and Z-138 with IC50 values ranging in 68-340 nM and EC50 values ranging in 150-507 nM, PTC596 at concentration of 300 nM induced activation, caspase-3 cleavage, mitochondrial membrane potential loss and MCL-1 levels decreased in Z-138 and REC-1 cells. These data suggested PTC596 induces mitochondrial apoptosis in MCL cells through down-regulation of MCL-1^[1]. PTC596 at concentration of 0.1 and 1μM reduced cell viability and induced a G2M arrest in human PDA lines Aspc1, Mia PaCa-2, and Panc1. PTC596 also induced the M-phase marker phospho-histone H3 (PH3) accumulation in these PDA cells. These data demonstrated that PTC596 acts as a potent inducer of mitotic arrest in multiple PDA cell lines^[2]. In vivo, administration of PTC596 at 15 mg/kg twice weekly led to a 48.9% reduction of bone marrow multiple myeloma infiltration and weekly treatment with PTC596 at a dose of 30 mg/kg led to a complete eradication of multiple myeloma cells in 5TGM.1 murine model of myeloma^[3]. Oral administration of PTC596 at 12.5 mg/kg twice a week for 45 days slowed tumor growth modestly in nu/nu mice bearing Capan-1 xenograft tumors. Oral administration of 17 mg/kg PTC596 did not affect survival, but the combination of the PTC596 and gemcitabine in a synergistic way improved survival in nu/nu mice bearing Capan-1 xenograft tumors^[2].
作用机制PTC596 induces phosphorylation of BMI-1 at two N-terminal sites, leading to accelerated degradation of BMI-1^[1].
参考文献

[1] Maeda A , Nishida Y , Weetall M , et al. Targeting of BMI-1 expression by the novel small molecule PTC596 in mantle cell lymphoma. Oncotarget, 2018, 9(47)
[2] Eberlesingh J A, Sagalovskiy I, Maurer H C, et al. Effective delivery of a microtubule polymerization inhibitor synergizes with standard regimens in models of pancreatic ductal adenocarcinoma. Clinical Cancer Research, 2019, 25(18): 5548-5560
[3] Bolomsky A, Muller J, Stangelberger K, et al. The anti-mitotic agents PTC-028 and PTC596 display potent activity in pre-clinical models of multiple myeloma but challenge the role of BMI-1 as an essential tumour gene. Br J Haematol, 2020

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.3790 mL
- 11.8952 mL
- 23.7903 mL
- 5 mM
- 0.4758 mL
- 2.3790 mL
- 4.7581 mL
- 10 mM
- 0.2379 mL
- 1.1895 mL
- 2.3790 mL

技术信息

CAS号

1610964-64-1

储存条件

粉末: Keep in dark place,Inert atmosphere,Room temperature

液体: -20°C:3-6 月 -80°C:12月

分子式

C19H13F5N6

运输

蓝冰

分子量

420.34

别名

PTC596

溶解度

DMSO	32.0 mg/mL (76.1 mM)
Water	insoluble

动物实验配方

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