| Identification | Back Directory | [Name]
5-Pyrimidinecarboxamide, 2-[[(3R,4R)-3-aminotetrahydro-2H-pyran-4-yl]amino]-4-[(4-methylphenyl)amino]-, hydrochloride (1:2) | [CAS]
2341796-81-2 | [Synonyms]
GSK143 dihydrochloride
5-Pyrimidinecarboxamide, 2-[[(3R,4R)-3-aminotetrahydro-2H-pyran-4-yl]amino]-4-[(4-methylphenyl)amino]-, hydrochloride (1:2) | [Molecular Formula]
C17H23ClN6O2 | [MOL File]
2341796-81-2.mol | [Molecular Weight]
378.86 |
| Chemical Properties | Back Directory | [storage temp. ]
4°C, away from moisture and light | [solubility ]
Soluble to 100 mM in water and to 100 mM in DMSO | [form ]
Solid | [color ]
Off-white to light yellow | [Water Solubility ]
H2O: 2mg/mL, clear (Warmed) |
| Hazard Information | Back Directory | [Uses]
GSK143 dihydrochloride is an orally active and highly selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.5. GSK143 dihydrochloride inhibits phosphorylated Erk (pErk: pIC50=7.1)[1]. GSK143 dihydrochloride reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice[2][3]. | [Biological Activity]
GSK143 is an orally activepotent and selective syk inhibitor (pIC50 = 7.5 or IC50 = 31.6 nM) with good selectivity over 66 protein kinasesincluding ZAP-70 (pIC50 = 4.7 or IC50 = 20 μM). GSK143 effectively inhibits anti-IgM induced Erk1/2 phosphorylation in Ramos cells (pIC50 = 7.1 or IC50 = 79.4 nM) and demonstrates in vivo efficacy in animal inflammatory disease modelsincluding reverse Arthus passive reaction (10 & 30 mg/kg po. in rats)postoperative ileus (POI13 or 10 mg/kg po. in mice)and chronic HDM-induced allergic airways inflammation (30 mg/kg/day po. in mice). | [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 T1/2 of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a Vss of 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.
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| 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 T1/2 of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a Vss of 4.1 L/kg.
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| [storage]
Store at -20°C | [References]
[1] John Liddle, et al. Discovery of GSK143, a Highly Potent, Selective and Orally Efficacious Spleen Tyrosine Kinase Inhibitor. Bioorg Med Chem Lett. 2011 Oct 15;21(20):6188-94. DOI:10.1016/j.bmcl.2011.07.082
[2] Abraham M Varghese, et al. Highly Selective SYK Inhibitor, GSK143, Abrogates Survival Signals in Chronic Lymphocytic Leukaemia. Br J Haematol. 2018 Sep;182(6):927-930. DOI:10.1111/bjh.14884
[3] Sjoerd H W van Bree, et al. Inhibition of Spleen Tyrosine Kinase as Treatment of Postoperative Ileus. Gut. 2013 Nov;62(11):1581-90. DOI:10.1136/gutjnl-2012-302615 |
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| Company Name: |
Merck KGaA
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| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
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