| 货号 (SKU) | 包装规格 | 是否现货 | 价格 | 数量 |
|---|---|---|---|---|
| P422209-1ml |
1ml |
现货  |
|
| 英文别名 | 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 |
|---|---|
| 规格或纯度 | Moligand™, 10mM in DMSO |
| 英文名称 | PRN1371 |
| 生化机理 | PRN1371 是一种不可逆的共价 FGFR1-4 激酶抑制剂，对 FGFR1、2、3、4 和 CSF1R 的 IC50 分别为 0.6、1.3、4.1、19.3 和 8.1 nM。 |
| 储存温度 | -80℃储存 |
| 运输条件 | 超低温冰袋运输 |
| 作用类型 | 抑制剂 |
| 作用机制 | 成纤维细胞生长因子受体 1 抑制剂；成纤维细胞生长因子受体 2 抑制剂；成纤维细胞生长因子受体 3 抑制剂；成纤维细胞生长因子受体 4 抑制剂 |
| 产品介绍 |
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%), <30% hERG inhibition at 1 μM, and good predicted ADME stability with BME reactivity Kd>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 < 15%). In SNU16 gastric cancer xenograft mouse model, Compound 34 induced a dose-dependent reduction in tumor volume and up to 68% tumor growth inhibition at the highest dose of 10 mg/kg b.i.d. following 27 days of treatment. All doses were well tolerated with no significant body weight loss. Cell Research(from reference) Cell lines：HUVECs Incubation Time：1 h |
| IC50 | FGFR1, IC50: 0.6 nM |
|---|---|
| ALogP | 3.438 |
| HBD Count | 1 |
| Rotatable Bond | 9 |
| 作用机制 | Action Type | target ID | Target Name | Target Type | Target Organism | Binding Site Name | 参考文献 |
|---|
| 分子类型 | 小分子 |
|---|---|
| IIUPAC Name | 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 |
| INCHI | 1S/C26H30Cl2N6O4/c1-5-20(35)33-11-9-32(10-12-33)7-6-8-34-24-16(15-30-26(29-2)31-24)13-17(25(34)36)21-22(27)18(37-3)14-19(38-4)23(21)28/h5,13-15H,1,6-12H2,2-4H3,(H,29,30,31) |
| InChi Key | PUIXMSRTTHLNKI-UHFFFAOYSA-N |
| Smiles | CNC1=NC=C2C=C(C(=O)N(C2=N1)CCCN3CCN(CC3)C(=O)C=C)C4=C(C(=CC(=C4Cl)OC)OC)Cl |
| Isomeric SMILES | CNC1=NC=C2C=C(C(=O)N(C2=N1)CCCN3CCN(CC3)C(=O)C=C)C4=C(C(=CC(=C4Cl)OC)OC)Cl |
| PubChem CID | 118295624 |
| 分子量 | 561.46 |
| DMSO(mg / mL) Max Solubility | 100 |
|---|---|
| DMSO(mM) Max Solubility | 178.107078 |
| Water(mg / mL) Max Solubility | ＜1 |
| 分子量 | 561.500 g/mol |
| XLogP3 | 3.500 |
| 氢键供体数Hydrogen Bond Donor Count | 1 |
| 氢键受体数Hydrogen Bond Acceptor Count | 8 |
| 可旋转键计数Rotatable Bond Count | 9 |
| 精确质量Exact Mass | 560.171 Da |
| 单同位素质量Monoisotopic Mass | 560.171 Da |
| 拓扑极表面积Topological Polar Surface Area | 100.000 Ų |
| 重原子数Heavy Atom Count | 38 |
| 形式电荷Formal Charge | 0 |
| 复杂度Complexity | 870.000 |
| 同位素原子数Isotope Atom Count | 0 |
| 定义的原子立体中心计数Defined Atom Stereocenter Count | 0 |
| 未定义的原子立体中心计数Undefined Atom Stereocenter Count | 0 |
| 定义的键立体中心计数Defined Bond Stereocenter Count | 0 |
| 未定义的键立体中心计数Undefined Bond Stereocenter Count | 0 |
| 所有立体化学键的总数The total count of all stereochemical bonds | 0 |
| 共价键合单元计数Covalently-Bonded Unit Count | 1 |
| 象形图 | GHS07 |
|---|---|
| 信号词 | 警告 |
| 危险声明 |
H302: 吞食有害 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 |
| 预防措施声明 |
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。 |
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