product name CL-387785 (EKI-785)
Description: CL-387785 (also known as EKI-785) is an irreversible, and selective EGFR inhibitor with IC50 of 370 pM. CL-387785 covalently binds to EGFR. It blocked EGF-stimulated autophosphorylation of the receptor in cells (IC50 approximately 5 nM), inhibited cell proliferation (IC50 = 31-125 nM) primarily in a cytostatic manner in cell lines that overexpress EGF-R or c-erbB-2, and profoundly blocked the growth of a tumor that overexpresses EGF-R in nude mice.
References: Biochem Pharmacol. 1999 Apr 15;57(8):917-25; Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1521-6.
717.18
Formula
C24H25ClFN5O3.2C4H4O4
CAS No.
194423-06-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (139.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
5% DMSO+30% PEG 300+ddH2O: 28 mg/mL
Synonyms
BIBW 2992
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19416480
| In Vitro |
In vitro activity: CL-387785 blocks EGF-stimulated autoposphorylation of the receptor in cells (IC50, 5 nM), In cell lines that overexpress EGF-R or c-erbB-2, CL-387785 inhibits cell proliferation (IC50, 31 nM) primarily in a cytostatic manner. Kinase Assay: 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 H2O 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. Cell Assay: MTS assays are performed with the CellTiter 96@ AQueous One solution proliferation kit. A total of 10,000 cells (Ba/F3-E709K, Ba/F3-l858r or Ba/F3-ERBB2 cells) per well in 96-well flat-bottomed plates are incubated with various concentrations of inhibitors for 48 h. The IC50 is determined from dose–response curves using XLfit4. |
|---|---|
| In Vivo | In nude mice overexpressed EGF-R, CL-387785 (80 mg/kg/day, p.o.) profoundly blocks the growth of tumor. In murine models of autosomal recessive polycystic kidney disease (ARPKD), treatment of Balb/c-bpk/bpk (BPK) mice with CL-387785 (90 mg/kg, i.p.) results in a marked reduction of collecting tubule cystic lesions, improved renal function, decreased biliary epithelial abnormalities, and prolonged life span. Doses of CL-387785 as low as 25 mg/kg reduces the growth of HCA-7-induced xenograft tumor, and a dose of 100 mg/kg prevents tumor growth entirely. Dose of 50 mg/kg CL-387785 is effective at reducing the growth of HCT-116-induced xenograft tumor. |
| Animal model | Nude mice bearing human CRC cell tumor |
| Formulation & Dosage | Dissolved in DMSO; 100 mg/kg; i.p. injection |
| References | Biochem Pharmacol. 1999 Apr 15;57(8):917-25; Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1521-6. |
