GSK143 dihydrochloride 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 dihydrochloride 抑制 Erk 磷酸化 (pErk: pIC₅₀=7.1)。GSK143 dihydrochloride 可以减轻炎症，并防止小鼠肠道肌层中免疫细胞的募集。

GSK143 dihydrochloride is an orally active and highly selective spleen tyrosine kinase (SYK) inhibitor with a pIC 50 of 7.5. GSK143 dihydrochloride inhibits phosphorylated Erk (pErk: pIC 50 =7.1). GSK143 dihydrochloride reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice.

Solid

pIC50: 7.5 (SYK) and 7.1 (pErk)

GSK143 dihydrochloride (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).
GSK143 dihydrochloride (10-10000 nM; every 24 hours for 3 days) has an IC50 of 323 nM in CLL cells. GSK 143 dihydrochloride (1 μM; 30 mins) abrogates early signalling events including SYK phosphorylation and calcium flux.
GSK143 dihydrochloride (0.1-10 μM; for 30 min) reduces cytokine expression in bone marrow derived macrophages in a concentration-dependent manner.
has not independently confirmed the accuracy of these methods. They are for reference only.

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.
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.
GSK143 (iv of 1 mg/kg; po of 3 mg/kg) has a T 1/2 of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a V ss of 4.1 L/kg in rats.
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture and light In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

[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.
[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.

In Vitro: H₂O : 100 mg/mL (240.78 mM; Need ultrasonic)DMSO : ≥ 50 mg/mL (120.39 mM)