PF-06700841 P-Tosylate是一种强效的双重Janus激酶1（JAK1）和TYK2抑制剂，IC50值分别为17nM和23nM。
Cas No.:2140301-96-6
Sample solution is provided at 25 µL, 10mM.
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PF-06700841 P-Tosylate is a potent dual Janus kinase 1 (JAK1) and TYK2 inhibitor with IC50 values of 17nM and 23nM, respectively [1]. PF-06700841 P-Tosylate inhibits JAK-dependent signaling at multiple points in the pathogenic cycle, including keratinocyte signaling, maintenance of inflammatory T-cell infiltrate, and direct inhibition of TYK2-dependent IL-23 signaling[2]. PF-06700841 P-Tosylate has been widely used to attenuate both cutaneous and muscular inflammation in different models[3].
In vitro, PF-06700841 P-Tosylate pretreatment at 10µM for 1h inhibited IFNγ-induced nitrite production and cytokine transcription in Raw264.7 cells[4]. PF-06700841 P-Tosylate (20nM) treatment for 24h significantly inhibited the proliferation, migration, and invasion effects of hyperin on HTR-8/SVneo cells[5].
In vivo, PF-06700841 P-Tosylate treatment via oral administration at a dose of 3mg/kg/day for 3 days significantly mitigated lipopolysaccharide (LPS)-induced neutrophil inflammation in mice[6]. Oral administration of PF-06700841 P-Tosylate at a dose of 30mg/kg/day for 3 consecutive days significantly alleviated disease severity in a rat model of adjuvant-induced arthritis (AIA)[7].
References:
[1] Li Y, Chen J, Bolinger A A, et al. Target-based small molecule drug discovery towards novel therapeutics for inflammatory bowel diseases[J]. Inflammatory bowel diseases, 2021, 27(Supplement_2): S38-S62.
[2] Page K M, Suarez-Farinas M, Suprun M, et al. Molecular and cellular responses to the TYK2/JAK1 inhibitor PF-06700841 reveal reduction of skin inflammation in plaque psoriasis[J]. Journal of Investigative Dermatology, 2020, 140(8): 1546-1555. e4.
[3] Krueger J G, McInnes I B, Blauvelt A. Tyrosine kinase 2 and Janus kinase‒signal transducer and activator of transcription signaling and inhibition in plaque psoriasis[J]. Journal of the American Academy of Dermatology, 2022, 86(1): 148-157.
[4] Romero-Ramírez L, García-Rama C, Mey J. Janus kinase inhibitor brepocitinib rescues myelin phagocytosis under inflammatory conditions: in vitro evidence from microglia and macrophage cell lines[J]. Molecular Neurobiology, 2024, 61(9): 6423-6434.
[5] Mu Z, Shen S, Tang L, et al. Hyperin promotes proliferation, migration, and invasion of HTR-8/SVneo trophoblast cells via activation of JAK1/STAT3 pathway in recurrent spontaneous abortions[J]. Heliyon, 2023, 9(1).
[6] Nayak B B, Bärnthaler T, Rajesh R, et al. Brepocitinib, a selective TYK2/JAK1 inhibitor, mitigates neutrophilic inflammation and glucocorticoid receptor-β expression in COPD[J]. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2026.
[7] Fensome A, Ambler C M, Arnold E, et al. Dual inhibition of TYK2 and JAK1 for the treatment of autoimmune diseases: discovery of ((S)-2, 2-difluorocyclopropyl)((1 R, 5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl) amino) pyrimidin-4-yl)-3, 8-diazabicyclo [3.2. 1] octan-8-yl) methanone (PF-06700841)[J]. Journal of medicinal chemistry, 2018, 61(19): 8597-8612.
PF-06700841 P-Tosylate是一种强效的双重Janus激酶1（JAK1）和TYK2抑制剂，IC50值分别为17nM和23nM[1]。PF-06700841 P-Tosylate可在致病周期的多个节点抑制JAK依赖性信号传导，包括角质形成细胞信号传导、炎症性T细胞浸润的维持，以及直接抑制TYK2依赖性IL-23信号传导[2]。PF-06700841 P-Tosylate已被广泛用于减轻不同模型中的皮肤和肌肉炎症[3]。
在体外，使用10µM的PF-06700841 P-Tosylate预处理Raw264.7细胞1小时，抑制了IFNγ诱导的亚硝酸盐生成和细胞因子转录[4]。使用20nM的PF-06700841 P-Tosylate处理HTR-8/SVneo细胞24小时，显著抑制了hyperin对细胞的增殖、迁移和侵袭的效应 [5]。
在体内，每日口服给予3mg/kg剂量的PF-06700841 P-Tosylate，连续3天，显著减轻了脂多糖（LPS）诱导的小鼠中性粒细胞炎症[6]。连续3天每日口服给予30mg/kg剂量的PF-06700841 P-Tosylate，显著减轻了佐剂性关节炎（AIA）大鼠模型的疾病严重程度[7]。
| Cell experiment [1]: | |
Cell lines | Raw264.7 cells |
Preparation Method | HepG2 cells were cultured in DMEM medium supplemented with 5% heat-inactivated fetal bovine serum, 100units /ml penicillin, and 100µg/ml streptomycin at 37°C in a 5% CO2 incubator. HepG2 cells were seeded at a density of 6×104 cells/well in 96-well flat-bottom plates and cultured in DMEM medium containing 1% FBS for 24 hours. Cells were pretreated with PF-06700841 P-Tosylate (0.01, 0.05, 0.2, 1, and 10µM) at 1h before adding IFNγ (10ng/ml) and exposure for 24h. Nitrite production and cytokine expression were analyzed. |
Reaction Conditions | 0.01, 0.05, 0.2, 1, and 10µM; 1h |
Applications | PF-06700841 P-Tosylate treatment inhibited IFNγ-induced nitrite production and cytokine transcription in Raw264.7 cells. |
| Animal experiment [2]: | |
Animal models | Female C57BL/6 mice |
Preparation Method | 8-week-old female C57BL/6 mice were housed in a specific pathogen-free (SPF) animal house maintained at 23°C with a 12h light/dark cycle and free access to water and food. Mice received intranasal LPS (5µg) or saline (vehicle control) to induce acute lung inflammation, along with oral PF-06700841 P-Tosylate (3mg/kg) or saline, once daily for three days. On day 4, the mice were sacrificed under anesthesia induced with ketamine (10mg/ml) and xylazine (1mg/ml). Then, bronchoalveolar lavage fluid (BALF) and blood samples were collected for analysis. |
Dosage form | 3mg/kg/day for 3 days; p.o. |
Applications | PF-06700841 P-Tosylate treatment significantly mitigated LPS-induced neutrophil inflammation in mice. |
References: | |
| Cas No. | 2140301-96-6 | SDF | |
| 别名 | PF-06700841 P-Tosylate | ||
| 化学名 | ((S)-2,2-difluorocyclopropyl)(3-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone 4-methylbenzenesulfonate | ||
| Canonical SMILES | O=C([C@H]1C(F)(F)C1)N2C3CN(C4=NC(NC5=CN(C)N=C5)=NC=C4)CC2CC3.OS(=O)(C6=CC=C(C)C=C6)=O | ||
| 分子式 | C25H29F2N7O4S | 分子量 | 561.61 |
| 溶解度 | DMSO : 62.5 mg/mL (111.29 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7806 mL | 8.903 mL | 17.806 mL |
| 5 mM | 356.1 μL | 1.7806 mL | 3.5612 mL |
| 10 mM | 178.1 μL | 890.3 μL | 1.7806 mL |
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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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