PRN1371是FGFR1-4的不可逆性共价抑制剂，对于FGFR1, 2, 3, 4和CSF1R的IC50分别为0.6、1.3、4.1、19.3、和8.1 nM。 Information PRN1371 is an irreversible covalentFGFR1-4kinase inhibitor, withIC50sof 0.6, 1.3, 4.1, 19.3 and 8.1 nM for FGFR1, 2, 3, 4 and CSF1R, respectively. Targets FGFR1 (Cell-free assay); FGFR2 (Cell-free assay); FGFR3 (Cell-free assay); CSF1R (Cell-free assay); FGFR4 (Cell-free assay) 0.6 nM; 1.3 nM; 4.1 nM; 8.1 nM; 19.3 nM In vitro PRN1371 is an irreversible nanomolar inhibitor of FGFR1−4. PRN1371 presents a unique profile of high biochemical and cellular potency (FGFR1 IC50 = 0.6 nM, SNU16 IC50 = 2.6 nM), prolonged target engagement (FGFR1 occupancy 24 h = 96%), 100 μM. PRN1371 which maintained high FGFR1 occupancy with improved solubility and exceptional oral bioavailability. In vivo A rat iv (2 mg/kg) PK study of compound 34 showed rapid clearance (Cl = 160 ml/min/kg), yet dosing po (20 mg/kg) demonstrated high oral exposure (AUC = 4348 h·ng/mL) and a reasonable half-life (t1/2 = 3.8 h). PK studies of compound 34 in rat, dog, and cynomolgus monkey showed rapid iv clearance in all species; however there were large species differences in oral exposure and bioavailability for monkey compared to rat and dog. In rat, high exposure upon oral dosing (e.g., Cmax = 1785 ng/mL, AUC = 4348 ng·h/mL) and >100% bioavailability (F) suggested good absorption and partial saturation of clearance mechanisms at the 20 mg/kg dose. Unique to the rat, there is a large difference in half-life between the iv (t1/2 = 0.8 h) and po (t1/2 = 3.8 h) routes of administration, also indicative of possible saturation of a clearance mechanism upon oral dosing. In the dogs, the same methylcellulose suspension formulation used for the rat gave low oral absorption and bioavailability (F Cell Research(from reference) Cell lines：HUVECs Incubation Time：1 h
All
Chemical Reagents
Biomedicine
Organic raw materials
Inorganic chemical industry
intermediate
Agricultural chemicals
Auxiliaries and catalysts
Fragrances and Flavors
Dyes and Pigments
Daily chemical industry
PRN1371
Dangerous GoodsCAS number：1802929-43-6 molecular formula：C26H30Cl2N6O4
overview
compound introduction
Specs
| Chinese alias | - | ||
| English alias | CCG-270053 | C92492 | NSC801089 | NSC-801089 | s8578 | AC-35543 | GTPL9788 | HY-101768 | EX-A2927 | PRN 1371 [WHO-DD] | 6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-[3-(4-prop-2-enoylpiperazin-1-yl)propyl]pyrido[2,3-d]pyrimidin-7-one | BDBM28698 | ||
| CAS number | 1802929-43-6 | molecular formula | C26H30Cl2N6O4 |
| molecular weight | 561.46 g/mol | Exact mass | - |
| PSA | 100.000 Ų | logp | 3.438 |
numbering system
No numbering system information yet
physicochemical properties
No physical and chemical property information yet
Safety information
pictogram：
GHS07
Signal word：
Warning
Hazard Statement：
H315: 引起皮肤刺激 H319: 引起严重眼睛刺激 H335: 可能引起呼吸道刺激 H302: 吞食有害
Statement of Preventive Measures：
P261: 避免吸入灰尘/烟雾/气体/雾/蒸汽/喷雾 P305+P351+P338: 如进入眼睛：用水小心冲洗几分钟。如戴隐形眼镜并可方便地取出，取出隐形眼镜。继续冲洗。
Production methods and uses
No production method and use information yet
Related
upstream information
No upstream information yet
downstream information
No downstream information yet
MSDS
Found 0 shareMSDS
