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Dabogratinib (TYRA-300) is an orally active, selective FGFR3 inhibitor with an IC50 of 11 nM. Dabogratinib downregulates the FGFR3 and ERK1/2 signaling pathways, and induces tumor growth inhibition and regression in FGFR3-altered xenograft models. Dabogratinib promotes chondrocyte proliferation and differentiation, drives endochondral bone formation and overall body growth, partially restores long bone proportions, and improves craniofacial and spinal morphology. Dabogratinib (0.046 nM-3 μM; 2 h) induces dose-dependent downregulation of the FGFR3 downstream signaling pathway (assessed by pERK1/2 levels) in RT112/84, RT112/84-V555M and UM-UC-14 bladder cancer cell lines.
Dabogratinib (12.5 mg/kg; p.o.; twice daily) induces tumor regression in FGFR3::TACC3 fusion urothelial carcinoma xenograft models and FGFR3V555M urothelial carcinoma xenograft models. Dabogratinib (8-14 mg/kg; p.o.; once daily; 4 weeks) dose-dependently increases the growth rate of wild-type mice and promotes their long bone growth in vivo. Dabogratinib (1.2 mg/kg; s.c.; once daily; 15 days) promotes bone growth, improves skeletal proportions, optimizes growth plate structure, and increases the foramen magnum size in the Fgfr3Y367C/+ mouse model of achondroplasia (ACH).
| Molecular Weight | 559.47 |
| Formula | C25H24Cl2N6O3S |
| CAS Number | 2800223-30-5 |
| Solubility (25°C) | DMSO 60 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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