GSK143 是一种具有口服活性，高选择性的脾酪氨酸激酶 (SYK) 抑制剂，pIC50为 7.5。GSK143 抑制 Erk 磷酸化 (pErk:pIC50=7.1)。GSK143 可以减轻炎症，并防止小鼠肠道肌层中免疫细胞的募集。
| 生物活性 | GSK143 is an orally active and highly selectivespleen tyrosine kinase (SYK)inhibitor with apIC50of 7.5. GSK143 inhibits phosphorylatedErk(pErk:pIC50=7.1)[1]. GSK143 reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice[2][3]. |
| IC50& Target | pIC50: 7.5 (SYK) and 7.1 (pErk)[1] |
体外研究
(In Vitro) | GSK143 (compound 20) inhibits ZAP-70 (pIC50=4.7), LCK (pIC50=5.3), LYN (pIC50=5.4), JAK1/2/3 (pIC50=5.8/5.8/5.7), Aurora B (pIC50=4.8), hWB (pIC50=6.6), hERG (pIC50=4.7)[1].
GSK143 (10-10000 nM; every 24 h for 3 days) has an IC50of 323 nM in CLL cells. GSK 143 (1 μM; 30 mins) abrogates early signalling events including SYK phosphorylation and calcium flux[2].
GSK143 (0.1-10 μM; for 30 min) reduces cytokine expression in bone marrow derived macrophages in a concentration-dependent manner[3].
Cell Viability Assay[2] | Cell Line: | Chronic lymphocytic leukaemia (CLL) cells | | Concentration: | 10, 100, 1000, 10000 nM | | Incubation Time: | Every 24 h for 3 days | | Result: | Had an IC50of 323 nM. |
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体内研究
(In Vivo) | GSK143 (0.1-10 mg/kg; orally; 1.5 hours) reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis of 1 mg/kg[3].
GSK143 (3, 10, 30, 100 mg/kg; oral; 1 hour before ovalbumin challenge) reduces the cutaneous reverse passive Arthus reaction in a dose dependent manner by approximately 50% and 70% at 10 mg/kg and 30 mg/kg, respectively[2].
GSK143 (iv of 1 mg/kg; po of 3 mg/kg) has a T1/2of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a Vssof 4.1 L/kg in rats[1].
| Animal Model: | Wild type C57NL/BL6 mice, 10-12 weeks old[3] | | Dosage: | 0.1, 1, 3, 10 mg/kg | | Administration: | Orally; 1.5 hours before intestinal manipulation (IM) | | Result: | Reduced inflammation and prevented recruitment of immune cells in the intestinal muscularis. |
| Animal Model: | Male CD rats (175-200 g)[1] | | Dosage: | 1 mg/kg of iv; 3 mg/kg of po (Pharmacokinetic Analysis) | | Administration: | IV or PO | | Result: | Had a T1/2of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a Vssof 4.1 L/kg. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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