CCT196969_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Libraries

https://www.wendangku.net/doc/6a7222605.html, Data Sheet

BIOLOGICAL ACTIVITY:

CCT196969, a pan–Raf inhibitor, inhibits B–Raf with an IC 50 of 0.1 μM.

IC50 & Target: IC50: 0.1 μM (B–Raf)[1]

In Vitro: CCT196969 is a pan–Raf inhibitor with anti–SRC activity. CCT196969 is an orally available, well–tolerated B–Raf inhibitor that directly inhibits B–Raf V600E in cells. CCT196969 inhibits B–Raf at 100 nM and B–Raf V600E at 40 nM. It inhibits CRaf at 12 nM,SRC at 26 nM, and LCK at 14 nM. CCT196969 is active against melanoma and colorectal cancer cell lines that are mutant for B–Raf.

CCT196969 induces caspase 3 and PARP cleavage, demonstrating that it induces apoptosis [1]. In Vivo: CCT196969 is extremely well tolerated and does not produce any significant adverse effects in vivo . It inhibits the growth of NRAS mutant DO4 tumor xenografts in nude mice. CCT196969 inhibits ERK and SRC and induce tumor regression in a PDX from the resistant tumor without causing body weight loss in the mice [1].

PROTOCOL (Extracted from published papers and Only for reference)

Cell Assay:[1]Cultured cells are seeded into 96–well plates (2,000 cells per well). At 24 hr later, serial dilutions of the B–Raf inhibitors PLX4720 and SB590885, the MEK inhibitor PD184352, or compounds CCT241161 and CCT196969 are added. Cells are incubated for a further 72 hr, and viability is measured by CellTiter–Glo assays. Relative survival in the presence of drugs is normalized to the untreated controls after background subtraction [1].

Animal Administration:[1]Mouse: Tumors are established in female nude mice. Treatment is by oral gavage daily with vehicle (5%DMSO, 95% water), 90 mg/kg PLX4720, 20 mg/kg CCT196969, or 20 mg/kg CCT241161. All the inhibitors are administered 7

days/week, with no weekend break. Tumor size is determined by caliper measurements of tumor length, width, and depth; volume is calculated as volume = 0.5236×length×width×depth (in millimeters)[1].

References:

[1]. Girotti MR, et al. Paradox–breaking RAF inhibitors that also target SRC are effective in drug–resistant BRAF mutant melanoma. Cancer Cell. 2015 Jan 12;27(1):85–96.

Product Name:

CCT196969Cat. No.:

HY-12846CAS No.:

1163719-56-9Molecular Formula:

C 27H 24FN 7O 3Molecular Weight:

513.52Target:

Raf Pathway:

MAPK/ERK Pathway Solubility:

DMSO: ≥ 32 mg/mL

Caution: Product has not been fully validated for medical applications. For research use only.

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