ZM 336372 is a potent, selective ATP-competitive inhibitor of c-Raf in vitro (IC50 = 70 nM for inhibition of human c-Raf). The Ras/Raf-1 signalling pathway is a well-characterized system that links receptor tyrosine kinase (RTK) activation with changes in gene expression and cell behavior. Raf-1 is a serine/threonine protein kinase that phosphorylates and activates MAPK-kinase (MEK) in response to activation by Ras. ZM 336372 also inhibits SAPK2/p38 (IC50 = 2 μM). Selective over 17 other protein kinases including PKA, PKC, p42 MAPK, CDK1 and SAPK1/JNK (up to 50 μM). ZM 336372 causes growth inhibition, suppression of hormone secretion, and up-regulation of cell cycle inhibitors in a human hepatocellular carcinoma cell line.
Cell Experiment | |
---|---|
Cell lines | H727 and BON cells |
Preparation method | Cell Proliferation Assay Proliferation of H727 and BON cells after treatment with ZM336372 was measured using a 3,4-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (Sigma). Cells were trypsinized and plated in triplicate to 24-well plates and allowed to adhere overnight. Then, cells were treated with either 100 μmol/L ZM336372 or DMSO (2%) and incubated. Media were changed every 2 days with new treatment. At each time point, cell growth rates were analyzed after the addition of 3,4-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reagent to the cultured cells following manufacturer's instructions. Absorbance was determined using spectrophotometer at a wavelength of 540 nm. |
Concentrations | 100 μmol/L |
Incubation time | 10 days |
Animal Experiment | |
---|---|
Animal models | |
Formulation | |
Dosages | |
Administration |
Molecular Weight | 389.45 |
Formula | C23H23N3O3 |
CAS Number | 208260-29-1 |
Solubility (25°C) | DMSO 50 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[3] Hall-Jackson CA, et al. Chem Biol. Paradoxical activation of Raf by a novel Raf inhibitor.
Related Raf Products |
---|
Cyclorasin 9A5
Cyclorasin 9A5 is an 11-residue cell-permeable cyclic peptide that orthosterically inhibits the Ras-Raf protein interaction with an IC50 of 120 nM. |
R18
R18 is a peptide antagonists of 14-3-3, with a KD of 70-90 nM. |
PROTAC RAF degrader 1
PROTAC RAF degrader 1 is a PROTAC RAF degrader. |
B-Raf IN 15
B-Raf IN 15 is a BRAF inhibitor. |
Raf inhibitor 3
Raf inhibitor 3 is a Raf inhibitor. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.