Description
GDC-0853 is an orally bioavailable, selective, and reversible Bruton’s tyrosine kinase (BTK) inhibitor with IC
50s ranging from 2-9 nM for basophil activation, B cell receptor activation, and constitutive p-BTK activity in whole blood lysates. In rats, treatment for longer than 7 days leads to pancreatic toxicity but it does not occur in mice or dogs, even at higher doses. Formulations containing GDC-0853 were well-tolerated in Phase I clinical trials and are in additional clinical trials for rheumatoid arthritis, lupus erythematosus, lymphoma, and leukemia.
in vivo
Fenebrutinib (GDC-0853) dose-dependently reduces ankle thickness following once (0.06, 0.25, 1, 4, and 16 mg/kg QD; orally) or twice (0.125, 0.5, and 2 mg/kg BID; orally) daily in female Lewis rats with developing collagen-induced arthritis[2].
Fenebrutinib (0.2 mg/kg IV and 1.0 mg/kg PO; for rats) and (0.2 mg/kg IV and 0.5 mg/kg PO for dogs) demonstrates the half-lives (t1/2s) of 2.2 and 3.8 h In rats, and dogs, respectively[2].
| Animal Model: | Female Lewis rats with developing collagen-induced arthritis (CIA)[2] |
| Dosage: | 0.06, 0.25, 1, 4, and 16 mg/kg once daily (QD); 0.125, 0.5, and 2 mg/kg twice daily (BID) |
| Administration: | Dosed orally; for 16 days |
| Result: | Dose-dependently reduced ankle thickness following QD and BID dosing regimens. |
