Agerafenib
作者：齊岳
發布時間：2023-08-28
09:02:44
點擊數：
產品名稱：Agerafenib
產品描述：
| 產品描述 | CEP-32496 is a highly potent inhibitor of BRAF. |
| 靶點活性 | c-Kit:2 nM(Kd), PDGFRβ:2 nM(Kd), Abl1:3 nM(Kd), Lck:2 nM(Kd), RET:2 nM(Kd) |
| 體外活性 | 在Colo-205異種移植小鼠模型中CEP-32496（30 mg/kg,口服,BID）顯示腫瘤停滯和部分腫瘤消退（PR）的發生率為40％,而100 mg/kg劑量組顯示腫瘤停滯和PR的發生率為80％.每天兩次口服30 mg/kg CEP-32496處理腫瘤裂解物,在給藥后2小時和6小時,分別抑制50％和75％歸一化的pMEK,而給攜帶Colo-205移植瘤的小鼠模型用55 mg/kg CEP-32496處理2到10小時,抑制57％到75％pMEK.CEP-32496在多種臨床前物種中口服生物可利用（大鼠,狗和猴子> 95％）.100 mg/kg CEP-32496處理導致裸鼠中的BRAF（V600E）結腸癌異種移植物中的pMEK和pERK的抑制和持續的腫瘤停滯和退化.CEP-32496在小鼠,狗,猴和人肝微粒體制劑中表現出良好的穩定性,在所有測定中測得的固有清除率值<23（μL/分鐘）/ mg和t1/2> 60分鐘. |
| 體內活性 | CEP-32496抑制人類黑素瘤和結直腸癌細胞系中的MAPK/MEK磷酸化,IC50為78 nM和60 nM。CEP-32496抑制A375細胞(BRAFV600E) 增殖,EC50為78 nM。CEP-32496作用于腫瘤細胞系,對表達突變型BRAF的A375,SK-MEL-28,Colo-205,Colo-679和HT-144細胞比表達野生型BRAF的HCT116,Hs578T,LNCaP,DU145和PC-3細胞具有更敏感的細胞毒性作用。 |
| 激酶實驗 | Binding assay: Kinases are produced displayed on T7 phage or by expression in HEK-293 cells and tagged with DNA. Binding reactions are performed at room temperature for 1 hour, and the fraction of kinase not bound to test compound is determined by capture with an immobilized affinity ligand and quantitation by quantitative PCR. Each kinase is tested individually against CEP-32496. Kd values are determined using eleven serial 3-fold dilutions and presented as mean values from experiments performed in duplicate. Variability between individual values is less than 2-fold. |
| 細胞實驗 | Cells are seeded at 104 cells per well in DMEM with 10% fetal calf serum and allowed to attach. The cells are washed with PBS and switched to DMEM with 0.5% of serum and incubated overnight. CEP-32496 is then added at various concentrations with a final DMSO concentration of 0.5% and incubated for 72 h. At the end of incubation, a Cell Titer Blue is added per instructions, and incubation is continued for 3 hours. Remaining viable cells are quantified by measuring the strength of the fluorescence signal using SoftMax Pro (excitation at 560 nm and emission at 590 nm). IC50 values are derived using a 9-point curve fitted with Igor Pro and are presented as mean values from experiments performed in duplicate. Variability between individual values is less than 2-fold.(Only for Reference) |
| 別名 | CEP32496, CEP 32496, RXDX-105, CEP-32496 |
| 分子量 | 517.465 |
| 分子式 | C24H22F3N5O5 |
| CAS No. | 1188910-76-0 |
存儲
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
Ethanol: <1 mg/mL
DMSO: 9 mg/mL (17.39 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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