hSMG-1 inhibitor 11j是一种嘧啶衍生物，是一种强效且选择性的hSMG-1抑制剂，IC50值为0.11nM。
Cas No.:1402452-15-6
Sample solution is provided at 25 µL, 10mM.
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hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC50 value of 0.11nM [1]. hSMG-1 inhibitor 11j can inhibit the phosphorylation of UPF1 by SMG1, increase the abundance of sTARDBP, and participate in the regulation of nonsense-mediated RNA decay (NMD) [2]. hSMG-1 inhibitor 11j has been widely used in the regulation of exon junction complex (EJC) and in non-dependent and EJC-enhanced reporter gene systems[3].
In vitro, hSMG-1 inhibitor 11j treatment (0.3μM) for 2h significantly reduced the phosphorylation of UPF1 at the T28 site and enhanced the expression levels of co-stimulatory molecules Cd40 and Cd80 in bone marrow-derived dendritic cells (BMDCs) [4]. Treatment of fibroblasts with hSMG-1 inhibitor 11j (0.5μM) for 20 hours resulted in a significant increase in LNPK RNA levels[5]. Treatment with 9.6μM hSMG-1 inhibitor 11j for 72 hours can induce apoptosis in A549 cells, reduce the viability of tumor cells, and enhance radio-sensitivity[6].
In vivo, injecting a single dose of 6µg of hSMG-1 inhibitor 11j (dissolved in 25µl of physiological saline) into the hind paw of mice for three hours can induce mechanical pain in the mice without causing thermal hyperalgesia[7].
References:
[1] Gopalsamy A, Bennett E M, Shi M, et al. Identification of pyrimidine derivatives as hSMG-1 inhibitors[J]. Bioorganic & medicinal chemistry letters, 2012, 22(21): 6636-6641.
[2] Dykstra M M, Weskamp K, Gómez N B, et al. TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms[J]. Cell reports, 2025, 44(1).
[3] Kolakada D, Campbell A E, Galvis L B, et al. A system of reporters for comparative investigation of EJC-independent and EJC-enhanced nonsense-mediated mRNA decay[J]. Nucleic Acids Research, 2024, 52(6): e34-e34.
[4] Mino T, Iwai N, Endo M, et al. Translation-dependent unwinding of stem–loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs[J]. Nucleic acids research, 2019, 47(16): 8838-8859.
[5] Doss R M, Wirth S A, Pitsch J W, et al. Exon-skipping due to bi-allelic splice site mutations in the neurodevelopmental disease gene LNPK[J]. Human Genetics and Genomics Advances, 2026, 7(1).
[6] Gudikote J P, Cascone T, Poteete A, et al. Inhibition of nonsense-mediated decay rescues p53β/γ isoform expression and activates the p53 pathway in MDM2-overexpressing and select p53-mutant cancers[J]. Journal of Biological Chemistry, 2021, 297(5): 101163.
[7] De La Peña J B, Chase R, Kunder N, et al. Inhibition of nonsense-mediated decay induces nociceptive sensitization through activation of the integrated stress response[J]. Journal of Neuroscience, 2023, 43(16): 2921-2933.
hSMG-1 inhibitor 11j是一种嘧啶衍生物，是一种强效且选择性的hSMG-1抑制剂，IC50值为0.11nM[1]。hSMG-1 inhibitor 11j可抑制SMG1介导的UPF1磷酸化，增加sTARDBP的丰度，并参与无义介导的RNA衰变(NMD)的调控[2]。hSMG-1 inhibitor 11j已被广泛用于外显子连接复合体的调控以及非依赖性和EJC增强的报告基因系统中[3]。
在体外，使用0.3μM的hSMG-1 inhibitor 11j处理骨髓来源的树突状细胞(BMDCs) 2小时，显著降低了UPF1在T28位点的磷酸化，并增强了共刺激分子Cd40和Cd80的表达水平[4]。用0.5μM的hSMG-1 inhibitor 11j处理成纤维细胞20小时，导致LNPK的RNA水平显著增加[5]。用9.6μM的hSMG-1 inhibitor 11j处理A549细胞72小时，可诱导细胞凋亡，降低肿瘤细胞活力，并增强放射敏感性[6]。
在体内，向小鼠后爪单次注射6μg的hSMG-1 inhibitor 11j（溶于25μl生理盐水中）3小时，可诱发小鼠机械性疼痛，而不引起热痛觉过敏[7]。
| Cell experiment [1]: | |
Cell lines | Bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice |
Preparation Method | BMDCs were grown in DMEM medium supplemented with 10% fetal bovine serum, 100U/ml penicillin, and 0.1mg/ml streptomycin in 5% CO2 at 37°C. BMDCs from C57BL/6J mice were treated with or without 0.3μM hSMG-1 inhibitor 11j for 2h and stimulated with 10ng/ml Pam3CSK4 or 100ng/ml LPS for 24h and cytokine levels in culture supernatants were measured. |
Reaction Conditions | 0.3μM; 2h |
Applications | hSMG-1 inhibitor 11j treatment significantly enhanced the levels of IL-6 and TNF in BMDCs. |
| Animal experiment [2]: | |
Animal models | Swiss Webster mice |
Preparation Method | Swiss Webster mice (6 weeks old) were kept in temperature-controlled (21°C-25°C) and humidity-maintained (40%-70%) rooms with a 12-h light/dark cycle. Water and food were provided freely. Mice received an intra-plantar injection of hSMG-1 inhibitor 11j (6µg) dissolved in 25µl of physiological saline. Mice were then given 30min to habituate to the apparatus. Mechanical sensitivity was measured using calibrated von Frey filaments. von Frey filaments, with bending forces of 0.04, 0.07, 0.16, 0.4, 0.6, 1, 1.5, and 2G, were applied to the mouse hind paw's plantar surface for 1-3 s. If the mouse lifts, shakes, or licks the hind paw while the filament is being applied, a paw withdrawal response is recorded. Mechanical sensitivity was then assessed 3h after PGE2 injection. |
Dosage form | 6µg for once; intra-plantar injection |
Applications | hSMG-1 inhibitor 11j treatment induced mechanical pain in the mice. |
References: | |
| Cas No. | 1402452-15-6 | SDF | |
| 别名 | 嘧啶杂质1 | ||
| Canonical SMILES | O=S(C1=CC(NC2=NC=CC(C3=CC(C4=CC=C(NC(NC)=O)C=C4)=NC=C3)=N2)=CC=C1Cl)(N(CC)CC)=O | ||
| 分子式 | C27H28ClN7O3S | 分子量 | 566.07 |
| 溶解度 | 储存条件 | 4°C, away from moisture and light | |
| 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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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7666 mL | 8.8328 mL | 17.6657 mL |
| 5 mM | 353.3 μL | 1.7666 mL | 3.5331 mL |
| 10 mM | 176.7 μL | 883.3 μL | 1.7666 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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