| Hazard Information | Back Directory | [Description]
G-744 is a highly potent, selective for Btk inhibitor. G-774 is metabolically stable, well tolerated, and efficacious in an animal model of arthritis. G-744 prevents cellular functions in murine B-cells such as B-cell receptor (BCR)-mediated CD86 induction with an EC50 of 64nM. G-744 also inhibited BCR-stimulated B-cell proliferation in human B-cells (EC50 = 22 nM). In human monocytes, production of the inflammatory cytokine TNFα following activation with immune complexes was abrogated by G-744 (EC50 = 33 nM). In human whole blood, G-744 demonstrated potent inhibition of BCR-stimulated CD69 expression on Bcells with an EC50 of 87 nM. | [Uses]
G-744 is a highly potent, selective and orally active Btk inhibitor with an IC50 of 2 nM. G-744 is metabolically stable, well tolerated and efficacious to treat arthritis[1]. | [in vivo]
G-744 (6.25/12.25/25 mg/kg, p.o., b.i.d., daily) protects Lewis rats from collagen-induced arthritis dose-dependently[1]. | Animal Model: | Female Lewis rat based CIA models[1]. | | Dosage: | 6.25, 12.25, 25 mg/kg. | | Administration: | Orally, b.i.d., daily for 17 days. | | Result: | All three doses resulted in a significant dose-dependent inhibition of ankle thickness between day 10 and day 17 (onset of increase in ankle diameter on day 9). |
| [References]
[1] Wang X, et al. Discovery of Potent and Selective Tricyclic Inhibitors of Bruton's Tyrosine Kinase with Improved Druglike Properties. ACS Med Chem Lett. 2017 May 3;8(6):608-613. DOI:10.1021/acsmedchemlett.7b00103 |
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