NP-12
(Synonyms: NP-12) 目录号 : GC36767
A PL-1/PD-L interaction inhibitor
Cas No.:1353563-85-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
AUNP-12 is an inhibitor of the interaction between programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2.1 It inhibits binding of soluble PD-1 to HEK293 cells expressing human PD-L2 (EC50 = 0.72 nM). AUNP-12 reverses PD-L1-induced inhibition of proliferation of PMA-stimulated, PD-1-expressing rat peripheral blood mononuclear cells (PBMCs; EC50 = 0.41 nM). It reduces tumor growth and lung metastasis by 44 and greater than 60%, respectively, in a B16/F10 mouse melanoma model when administered at a dose of 5 mg/kg per day.
1.Sasikumar, P.G.N., Ramachandra, M., Vadlamani, S.K., et al.Immunosuppression modulating compounds(2011)
| Cas No. | 1353563-85-5 | SDF | |
| 别名 | NP-12 | ||
| 分子式 | C142H226N40O48 | 分子量 | 3261.55 |
| 溶解度 | Water: soluble | 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 | 0.3066 mL | 1.533 mL | 3.066 mL |
| 5 mM | 0.0613 mL | 0.3066 mL | 0.6132 mL |
| 10 mM | 0.0307 mL | 0.1533 mL | 0.3066 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。
Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling Axis
Front Immunol 2018 Nov 5;9:2527.PMID:30455692DOI:10.3389/fimmu.2018.02527.
Parkinson's disease (PD) is a common neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Neuroinflammation induced by over-activation of microglia leads to the death of dopaminergic neurons in the pathogenesis of PD. Therefore, downregulation of microglial activation may aid in the treatment of PD. Polydatin (PLD) has been reported to pass through the blood-brain barrier and protect against motor degeneration in the SN. However, the molecular mechanisms underlying the effects of PLD in the treatment of PD remain unclear. The present study aimed to determine whether PLD protects against dopaminergic neurodegeneration by inhibiting the activation of microglia in a rat model of lipopolysaccharide (LPS)-induced PD. Our findings indicated that PLD treatment protected dopaminergic neurons and ameliorated motor dysfunction by inhibiting microglial activation and the release of pro-inflammatory mediators. Furthermore, PLD treatment significantly increased levels of p-AKT, p-GSK-3βSer9, and Nrf2, and suppressed the activation of NF-κB in the SN of rats with LPS-induced PD. To further explore the neuroprotective mechanism of PLD, we investigated the effect of PLD on activated microglial BV-2 cells. Our findings indicated that PLD inhibited the production of pro-inflammatory mediators and the activation of NF-κB pathways in LPS-induced BV-2 cells. Moreover, our results indicated that PLD enhanced levels of p-AKT, p-GSK-3βSer9, and Nrf2 in BV-2 cells. After BV-2 cells were pretreated with MK2206 (an inhibitor of AKT), NP-12 (an inhibitor of GSK-3β), or Brusatol (BT; an inhibitor of Nrf2), treatment with PLD suppressed the activation of NF-κB signaling pathways and the release of pro-inflammatory mediators in activated BV-2 cells via activation of the AKT/GSK3β-Nrf2 signaling axis. Taken together, our results are the first to demonstrate that PLD prevents dopaminergic neurodegeneration due to microglial activation via regulation of the AKT/GSK3β-Nrf2/NF-κB signaling axis.
Effects of nonylphenols on embryonic development and metamorphosis of Xenopus laevis: FETAX and amphibian metamorphosis toxicity test (OECD TG231)
Environ Res 2019 Jul;174:14-23.PMID:31022611DOI:10.1016/j.envres.2019.04.010.
Nonylphenols (NPs) are a group of endocrine-disrupting surfactants that mimic estrogen. To determine the developmental toxicity and thyroid-disrupting effect of NPs, the effects of exposure to nonylphenol (NP), 4-nonylphenol (4-NP), and nonylphenol ethoxylate (NP-12) were examined according to the frog embryo teratogenesis assay-Xenopus (FETAX) and Organization for Economic Co-operation and Development test guidelines 231 (TG231). In FETAX, the LC50 values of NP, 4-NP, and NP-12 were 59.14 mg/L, 10.13 mg/L, and 14.60 mg/L, respectively. At 10.0 mg/L, NP, 4-NP, and NP-12 significantly decreased the total length of tadpoles, and NP and 4-NP increased gut malformation and bent tails. In surviving tadpoles, the EC50 values for malformation of NP, 4-NP, and NP-12 were 4.66, 6.51, and 13.08 mg/L, respectively. The teratogenic indices of NP, 4-NP, and NP-12 were 12.69, 1.56, and 1.08, respectively, suggesting the teratogenic potential of NP and 4-NP. In a range-finder assay for TG231, the 96-h LC50 values of NP, 4-NP, and NP-12 were 2.0, 2.0, and 10.57 mg/L, respectively. When NF stage 51 larvae were exposed for 21 days, larval growth was inhibited by NP, 4-NP, and NP-12 at 0.67, 0.07, and 0.37 mg/L, respectively. 4-NP at 0.07 mg/L accelerated the developmental stage and significantly increased hind limb length, while 0.67 mg/L 4-NP delayed the developmental stage and decreased hind limb length, suggesting a bimodal effect of 4-NP on metamorphosis. NP and NP-12 at test concentrations did not alter the larval stage, but NP-12 at 0.37 mg/L significantly decreased total length and tail length, suggesting growth inhibition in larvae. The total colloid area of thyroid follicles was significantly increased by 0.07 mg/L 4-NP but not by NP and NP-12, suggesting that 4-NP may interfere with thyroid function. Together, the developmental toxicity of NPs was in the following order: 4-NP, NP-12, and NP. 4-NP may alter metamorphosis driven by thyroid hormones in X. laevis.
Beyond the neurotransmitter-focused approach in treating Alzheimer's disease: drugs targeting beta-amyloid and tau protein
Aging Clin Exp Res 2009 Dec;21(6):386-406.PMID:20154508DOI:10.1007/BF03327445.
Drugs currently used to treat Alzheimer's Disease (AD) have limited therapeutic value and do not affect the main neuropathological hallmarks of the disease, i.e., senile plaques and neurofibrillar tangles. Senile plaques are mainly formed of beta-amyloid (Abeta), a 42-aminoacid peptide. Neurofibrillar tangles are composed of paired helical filaments of hyperphosphorylated tau protein. New, potentially disease-modifying, therapeutic approaches are targeting Abeta and tau protein. Drugs directed against Abeta include active and passive immunization, that have been found to accelerate Abeta clearance from the brain. The most developmentally advanced monoclonal antibody directly targeting Abeta is bapineuzumab, now being studied in a large Phase III clinical trial. Compounds that interfere with proteases regulating Abeta formation from amyloid precursor protein (APP) are also actively pursued. The discovery of inhibitors of beta-secretase, the enzyme that regulates the first step of the amyloidogenic metabolism of APP, has been revealed to be particularly difficult due to inherent medicinal chemistry problems, and only one compound (CTS-21166) has reached clinical testing. Conversely, several compounds that inhibit gamma-secretase, the pivotal enzyme that generates Abeta, have been identified, the most advanced being LY-450139 (semagacestat), now in Phase III clinical development. Compounds that stimulate alpha-secretase, the enzyme responsible for the non-amyloidogenic metabolism of APP, are also being developed, and one of them, EHT-0202, has recently entered Phase II testing. Potent inhibitors of Abeta aggregation have also been identified, and one of such compounds, PBT-2, has provided encouraging neuropsychological results in a recently completed Phase II study. Therapeutic approaches directed against tau protein include inhibitors of glycogen synthase kinase- 3 (GSK-3), the enzyme responsible for tau phosphorylation and tau protein aggregation inhibitors. NP-12, a promising GSK-3 inhibitor, is being tested in a Phase II study, and methylthioninium chloride, a tau protein aggregation inhibitor, has given initial encouraging results in a 50-week study. With all these approaches on their way, the hope for disease-modifying therapy in this devastating disease may become a reality in the next 5 years.
A Rationally Designed Peptide Antagonist of the PD-1 Signaling Pathway as an Immunomodulatory Agent for Cancer Therapy
Mol Cancer Ther 2019 Jun;18(6):1081-1091.PMID:31015307DOI:10.1158/1535-7163.MCT-18-0737.
Pioneering success of antibodies targeting immune checkpoints such as PD-1 and CTLA4 has opened novel avenues for cancer immunotherapy. Along with impressive clinical activity, severe immune-related adverse events (irAE) due to the breaking of immune self-tolerance are becoming increasingly evident in antibody-based approaches. As a strategy to better manage severe adverse effects, we set out to discover an antagonist targeting PD-1 signaling pathway with a shorter pharmacokinetic profile. Herein, we describe a peptide antagonist NP-12 that displays equipotent antagonism toward PD-L1 and PD-L2 in rescue of lymphocyte proliferation and effector functions. In preclinical models of melanoma, colon cancer, and kidney cancers, NP-12 showed significant efficacy comparable with commercially available PD-1-targeting antibodies in inhibiting primary tumor growth and metastasis. Interestingly, antitumor activity of NP-12 in a preestablished CT26 model correlated well with pharmacodynamic effects as indicated by intratumoral recruitment of CD4 and CD8 T cells, and a reduction in PD-1+ T cells (both CD4 and CD8) in tumor and blood. In addition, NP-12 also showed additive antitumor activity in preestablished tumor models when combined with tumor vaccination or a chemotherapeutic agent such as cyclophosphamide known to induce "immunologic cell death." In summary, NP-12 is the first rationally designed peptide therapeutic targeting PD-1 signaling pathways exhibiting immune activation, excellent antitumor activity, and potential for better management of irAEs.
Production of teicoplanin by Actinoplanes teichomyceticus in continuous fermentation
Biotechnol Bioeng 2002 Mar 5;77(5):589-98.PMID:11788956DOI:10.1002/bit.10137.
Production of the potent antibiotic teicoplanin by Actinoplanes teichomyceticus was studied in batch and in chemostat cultures. It is found that the producing strain deactivates to a non-producing strain named NP-12. This strain is used to find the growth kinetics of the A. teichomyceticus without interference from the product teicoplanin. In batch experiments with NP-12 grown on glucose at different initial concentrations and with different added amounts of teicoplanin, the strong inhibitory effect of teicoplanin was determined. These results obtained on NP-12 were validated in a series of chemostat experiments with the processing strain. All experiments in batch and in chemostat cultures were well represented by Monod kinetics with respect to the carbon and energy source (glucose) and with a substantial inhibitory effect of teicoplanin. Further experiments were made with the producing strain in a continuous reactor coupled to a microfilter that delivers a cell-free permeate. It was found that the derived kinetics almost exactly simulated the behavior of the cell recirculation reactor in addition to when the cell concentration in the reactor was more than four times higher than in the chemostat. For industrial production of teicoplanin, a continuous reactor with cell recirculation and working with a low effluent glucose concentration was by far the best mode of operation. Finally, the deactivation of the producing strain to NP-12 was modeled by a two-step deactivation mechanism. Deactivation was independent of dilution rate but dependent on the inoculum preparation and on the previous history of the inoculum.