General description
一种有效的可口服的VEGFR2抑制剂，IC50为3 nM。
The VEGF family including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PlGF signals through VEGFR1, VEGFR2, and VEGFR3 cell surface tyrosine kinase receptors that are located on the host vascular endothelium, lymphatic, and hematopoietic systems.
In vitro: BFH772 was highly effective at targeting VEGFR2 kinase, however, lost 500-fold potency on FLK-1, FLT-1, and FLT-4. BFH772 also targeted B-RAF, RET, and TIE-2, albeit with at least 40-fold lower potency. BFH772 inhibited the ligand induced autophosphorylation of RET, PDGFR, and KIT kinases. BFH772 was selective against the kinases of EGFR, ERBB2, INS-R, and IGF-1R and against the cytoplasmic BCR-ABL kinase .
In vivo: The dose response curves of BFH772 at 0.3, 1, and 3 mg/kg showed that even at the lowest concentrations, this naphthalene-1-carboxamide inhibited VEGF induced tissue weight and TIE-2 levels but only reached statistical significance at 1 mg/kg and above. Moreover, BFH772 at 3 mg/kg orally dosed once per day could potently inhibit melanoma growth (54-90% for primary tumor and 71-96% for metastasis tumor) when compared with control ratios .
包括VEGF-A，VEGF-B，VEGF-C，VEGF-D和PlGF在内的VEGF家族通过位于宿主血管内皮，淋巴和造血系统上的VEGFR1，VEGFR2和VEGFR3细胞表面酪氨酸激酶受体发出信号。
体外：BFH772在靶向VEGFR2激酶方面非常有效，但是在FLK-1，FLT-1和FLT-4上丧失了500倍的效力。 BFH772还针对B-RAF，RET和TIE-2，尽管其效价至少低40倍。 BFH772抑制配体诱导的RET，PDGFR和KIT激酶的自磷酸化。 BFH772对EGFR，ERBB2，INS-R和IGF-1R激酶以及细胞质BCR-ABL激酶具有选择性。
体内：BFH772在0.3、1和3 mg / kg时的剂量反应曲线表明，即使在最低浓度下，萘-1-甲酰胺也能抑制VEGF诱导的组织重量和TIE-2水平，但仅在1毫克/千克及以上。此外，与对照组相比，每天口服3 mg / kg BFH772可以有效抑制黑色素瘤的生长（原发肿瘤为54-90％，转移肿瘤为71-96％）。
Properties
| Iupac Name： | 6-((6-(hydroxymethyl)pyrimidin-4-yl)oxy)-N-(3-(trifluoromethyl)phenyl)-1-naphthamide |
| Inchi Code | 1S/C23H16F3N3O3/c24-23(25,26)15-4-2-5-16(10-15)29-22(31)20-6-1-3-14-9-18(7-8-19(14)20)32-21-11-17(12-30)27-13-28-21/h1-11,13,30H,12H2,(H,29,31) |
| Inchi Key | JNLSTLQFDDAULK-UHFFFAOYSA-N |
安全信息
