Chemical Properties | Back Directory | [Boiling point ]
1125.6±65.0 °C(predicted) | [density ]
1.481±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
10.83±0.40(predicted) | [color ]
Light yellow to yellow |
Hazard Information | Back Directory | [Uses]
LC-MB12 is an orally active PROTAC compound targets FGFR2 degradation with a DC50 of 11.8 nM. LC-MB12 contains BGJ398 (a FGFR2 inhibitor), PROTAC linker and CRBN.LC-MB12 inhibits FGFR2 signaling in gastric cancer cells and has anti-tumor activity[1]. | [in vivo]
LC-MB12 (20 mg/kg/day, p.o., 15 days) inhibits tumor growth to 63.1% in SNU-16 xenograft models of nude mice[1].
LC-MB12 (20 mg/kg, p.o.) shows fast absorption (Cmax: 2.6 h) and orally bioavailable (F: 13%) in mice[1].
LC-MB12 (20 mg/kg, p.o., 30 days) is well tolerated and has no apparent hepatotoxicity or nephrotoxicity in mice[1].
In Vivo PK Properties of LC-MB12[1]
parameter | T1/2 | Tmax (ng?h/mL) | Cmax | AUC(0-∞)1/2 | Vss (h) | CL | F | unit | h | h | ng/mL | h*ng/mL | mL/kg | mL/h/kg | % | iv (3 mg/kg) | 0.97 | 0.083 | 655.29 | 421.61 | 6233.19 | 7289.12 | / | po (20 mg/kg) | 1.47 | 2.67 | 82.07 | 387.27 | / | / | 13.07 |
Animal Model: | SNU-16 xenografted in BALB/c-nu mice[1]. | Dosage: | 20 mg/kg/day | Administration: | oral administration (p.o.) 15 days | Result: | Achieved 63.1% tumor growth inhibition innocuously.
Inhibited FGFR phosphorylation and total FGFR2 protein and decreased phosphorylation levels of downstream pPLCγ and ERK1/2.
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FGFR2: 11.8 nM (DC50) | [References]
[1] Ma L, et al. Discovery of a Selective and Orally Bioavailable FGFR2 Degrader for Treating Gastric Cancer. J Med Chem. 2023 Jun 8;66(11):7438-7453. DOI:10.1021/acs.jmedchem.3c00150 |
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