Mardepodect
(Synonyms: 2-[[4-[1-甲基-4-(4-吡啶基)-1H-吡唑-3-基]苯氧基]甲基]-喹啉,PF-2545920) 目录号 : GC36540
A potent inhibitor of PDE10A
Cas No.:898562-94-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
PF-2545920 is a potent inhibitor of phosphodiesterase 10A (PDE10A; IC50 = 1.26 nM for the human recombinant enzyme).1 It is selective for PDE10A over other PDEs with IC50 values ranging from 1.7 to >10 μM. In vivo, PF-2545920 (0.1-3 mg/kg, i.p.) increases cAMP and cGMP production as well as phosphorylation of CREB and GluR1 in mouse striatum in a dose-dependent manner. It reduces climbing behavior induced by apomorphine in mice (ID50 = 0.375 mg/kg) and disrupts the conditioned avoidance response in mice and rats (ID50s = 0.441 and 1.079 mg/kg, respectively). PF-2545920 reverses deficits in prepulse inhibition and social odor recognition induced by (+)-MK-801 in rats. Formulations containing PF-2545920 are under clinical investigation for the treatment of schizophrenia and Huntington's disease.
1.Grauer, S.M., Pulito, V.L., Navarra, R.L., et al.Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophreniaJ. Pharmacol. Exp. Ther.331(2)574-590(2009)
| Cas No. | 898562-94-2 | SDF | |
| 别名 | 2-[[4-[1-甲基-4-(4-吡啶基)-1H-吡唑-3-基]苯氧基]甲基]-喹啉,PF-2545920 | ||
| Canonical SMILES | CN(N=C1C2=CC=C(OCC3=NC4=CC=CC=C4C=C3)C=C2)C=C1C5=CC=NC=C5 | ||
| 分子式 | C25H20N4O | 分子量 | 392.45 |
| 溶解度 | DMSO: ≥ 45 mg/mL (114.66 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5481 mL | 12.7405 mL | 25.481 mL |
| 5 mM | 0.5096 mL | 2.5481 mL | 5.0962 mL |
| 10 mM | 0.2548 mL | 1.274 mL | 2.5481 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Transcriptomics-Based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma Cells
Cancers (Basel) 2021 Jul 27;13(15):3780.PMID:34359681DOI:PMC8345128
We have used three established human glioblastoma (GBM) cell lines-U87MG, A172, and T98G-as cellular systems to examine the plasticity of the drug-induced GBM cell phenotype, focusing on two clinical drugs, the phosphodiesterase PDE10A inhibitor Mardepodect and the multi-kinase inhibitor Regorafenib, using genome-wide drug-induced gene expression (DIGEX) to examine the drug response. Both drugs upregulate genes encoding specific growth factors, transcription factors, cellular signaling molecules, and cell surface proteins, while downregulating a broad range of targetable cell cycle and apoptosis-associated genes. A few upregulated genes encode therapeutic targets already addressed by FDA approved drugs, but the majority encode targets for which there are no approved drugs. Amongst the latter, we identify many novel druggable targets that could qualify for chemistry-led drug discovery campaigns. We also observe several highly upregulated transmembrane proteins suitable for combined drug, immunotherapy, and RNA vaccine approaches. DIGEX is a powerful way of visualizing the complex drug response networks emerging during GBM drug treatment, defining a phenotypic landscape which offers many new diagnostic and therapeutic opportunities. Nevertheless, the extreme heterogeneity we observe within drug-treated cells using this technique suggests that effective pan-GBM drug treatment will remain a significant challenge for many years to come.