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Chemical Structure| 1610964-64-1 同义名 : PTC596
CAS号 : 1610964-64-1
货号 : A602809
分子式 : C19H13F5N6
纯度 : 99%+
分子量 : 420.339
MDL号 : MFCD30489439
存储条件：

Pure form Keep in dark place,Inert atmosphere,Room temperature

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 16 mg/mL(38.06 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
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].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.38mL

0.48mL

0.24mL

11.90mL

2.38mL

1.19mL

23.79mL

4.76mL

2.38mL
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