CL-387785 是一种不可逆的EGFR抑制剂，IC50为 370 pM。

CL-387785(EKI785; WAY-EKI 785) is an irreversible inhibitor of EGFR（IC50： 370+/-120 pM）; is able to overcome resistance caused by the T790M mutation on a functional level.

CL-387785（50 mg/kg）对HCT-116诱导的异种移植瘤生长具有明显抑制作用.在表达EGF-R的裸鼠体内,CL-387785（80 mg/kg/day,p.o.）有效抑制肿瘤生长.在常染色体隐性遗传性多囊肾疾病小鼠模型中,CL-387785（90 mg/kg,i.p.）处理Balb/c-bpk/bpk (BPK)小鼠,可使集合小管囊性病变显著降低,改善肾功能,使胆管上皮细胞异常降低,延长生存期.CL-387785（25 mg/kg）能够降低HCA-7诱导的异种移植瘤生长,100 mg/kg时可完全抑制肿瘤生长.

CL-387785可使细胞中EGF-介导的受体自磷酸化被阻断（IC50：5 nM）。在过表达EGF-R或c-erbB-2的细胞系中,CL-387785主要以细胞抑制剂的方式抑制细胞增殖（IC50：31 nM）。

Liquid scintillation: Stock solutions of 500 μM CL-387785 (prepared in 100% DMSO) are diluted to the desired concentration with 30 mM HEPES, pH 7.4. Ten microliters of CL-387785 at various concentrations are incubated with 3 μL of recombinant enzyme (1:120 dilution in 100 mM HEPES, pH 7.4) on ice for 10 min. Then, 5 μL peptide (400 μM final concentration of RR-SRC composed of Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly), 10 μL of 4× reaction buffer containing 50 mM HEPES, pH 7.4, 80 μM ATP, 40 mM MnCl2, and 200 μM sodium orthovanadate. 0.30 μL [33P]ATP ( >2500 Ci/mmol), and 12 μL Water are added. After incubation for 90 min at room temperature, the entire volume is spotted onto precut P81 filter papers. The filter discs are washed two times with 0.5% phosphoric acid, and radioactivity is measured using a liquid scintillation counter. Under these conditions, the specific activity of EGF-R kinase is approximately 0.50 pmol/mg/min.

MTS assays are performed with the CellTiter 96@ AQueous One solution proliferation kit. A total of 10,000 cells per well in 96-well ?at-bottomed plates are incubated with various concentrations of inhibitors for 48 h. The IC50 is determined from dose–response curves using XL?t4.(Only for Reference)

194423-06-8

C18H13BrN4O

381.233

EKI-785;WAY-EKI 785;CL-387785

Ethanol:<1 mgml
DMSO:59 mg/mL (154.8 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years