Home >> Research Area >>MAPK Signaling>>Raf>> CEP-32496 hydrochloride

CEP-32496 hydrochloride

B-Raf/C-Raf inhibitor,highly potent CAS# 1227678-26-3

CEP-32496 hydrochloride

Catalog No. BCC1468----Order now to get a substantial discount!

Product Name & Size Price Stock
CEP-32496 hydrochloride: 5mg $322 In Stock
CEP-32496 hydrochloride: 10mg Please Inquire In Stock
CEP-32496 hydrochloride: 20mg Please Inquire Please Inquire
CEP-32496 hydrochloride: 50mg Please Inquire Please Inquire
CEP-32496 hydrochloride: 100mg Please Inquire Please Inquire
CEP-32496 hydrochloride: 200mg Please Inquire Please Inquire
CEP-32496 hydrochloride: 500mg Please Inquire Please Inquire
CEP-32496 hydrochloride: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of CEP-32496 hydrochloride

Number of papers citing our products

Chemical structure

CEP-32496 hydrochloride

3D structure

Chemical Properties of CEP-32496 hydrochloride

Cas No. 1227678-26-3 SDF Download SDF
PubChem ID 56954675 Appearance Powder
Formula C24H23ClF3N5O5 M.Wt 553.92
Type of Compound N/A Storage Desiccate at -20°C
Synonyms RXDX-105 hydrochloride; Agerafenib hydrochloride
Solubility DMSO
Chemical Name 1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea;hydrochloride
SMILES CC(C)(C1=CC(=NO1)NC(=O)NC2=CC(=CC=C2)OC3=NC=NC4=CC(=C(C=C43)OC)OC)C(F)(F)F.Cl
Standard InChIKey XCZIYUDQUDWQHI-UHFFFAOYSA-N
Standard InChI InChI=1S/C24H22F3N5O5.ClH/c1-23(2,24(25,26)27)19-11-20(32-37-19)31-22(33)30-13-6-5-7-14(8-13)36-21-15-9-17(34-3)18(35-4)10-16(15)28-12-29-21;/h5-12H,1-4H3,(H2,30,31,32,33);1H
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of CEP-32496 hydrochloride

DescriptionCEP-32496 hydrochloride is a highly potent inhibitor of wild-type BRAF, V600E mutant BRAF and c-Raf with Kd values of 14 nM, 36 nM and 39 nM, respectively.
Targetswild-type BRAFV600E mutant BRAFc-Raf   
IC5014 nM (Kd)36 nM (Kd)39 nM (Kd)    

Protocol

Kinase Assay [1]
KINOMEscan competition binding assays are performed. Kinases are produced displayed on T7 phage or by expression in HEK-293 cells and tagged with DNA. Binding reactions are performed at rt for 1 h, and the fraction of kinase not bound to test compound (e.g., CEP-32496) is determined by capture with an immobilized affinity ligand and quantitation by quantitative PCR. Each kinase is tested individually against each compound. 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[1].

Cell Assay [1]
A375 cells are seeded at 10,000 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. The test compounds (e.g., CEP-32496; 10 μM) are 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 h. 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 and are presented as mean values from experiments performed in duplicate[1].

Animal Administration [1]
Mice[1] Six to eight week old athymic nu/nu nude mice (20-25 g) are inoculated subcutaneously with Colo-205 tumor cells (1×106/mouse) in the right flank. Upon reaching an average tumor volume of 150-200 mm3 (10-12 days post implantation), animals are randomized into treatment groups (n=10 mice/group). Each group is dosed orally for 14 days with either vehicle only (22% HPβCD) or with CEP-32496 at 10, 30, or 100 mg/kg twice daily (BID), and each dose of drug is given in a volume of 0.1 mL per 20 g of body weight, adjusted for the body weight of the animal. Tumor volumes are measured three times weekly using vernier calipers, and volumes are calculated[1].

References:
[1]. Rowbottom MW, et al. Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E.

CEP-32496 hydrochloride Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

CEP-32496 hydrochloride Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of CEP-32496 hydrochloride

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 1.8053 mL 9.0266 mL 18.0531 mL 36.1063 mL 45.1329 mL
5 mM 0.3611 mL 1.8053 mL 3.6106 mL 7.2213 mL 9.0266 mL
10 mM 0.1805 mL 0.9027 mL 1.8053 mL 3.6106 mL 4.5133 mL
50 mM 0.0361 mL 0.1805 mL 0.3611 mL 0.7221 mL 0.9027 mL
100 mM 0.0181 mL 0.0903 mL 0.1805 mL 0.3611 mL 0.4513 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on CEP-32496 hydrochloride

CEP-32496 is a selective inhibitor of BRAFV600E with IC50 value of 669 nM [1].
BRAF is a member of Raf kinase family and plays an important role in sending signals (directing cell growth) inside cells. BRAF involves in regulating MAP kinase/ERKs signaling pathway and mutant BRAFV600E activates MAPK pathway, it has been shown that BRAF mutant BRAFV600E is correlated with several human cancers [2].
CEP-32496 is a potent BRAFV600E inhibitor and has a different selectivity with the reported BRAFV600E inhibitor RG7204. Using Ambit Kinomescan Assay, it was shown that CEP-32496 potently binding to RAF family with Kd value ranged from 14 to 39 nmol/L. When tested with a panel of BRAF mutant (A375, SK-MEL-28, Colo-679, HT-144, and Colon-205) cell lines, CEP-32496 showed a selective cytotoxicity profile against tumor cell lines with V600E mutant while had no effect on wild type cell lines (HCT116, Hs578T, LNCaP, DU145, PC-3) [1]. CEP-32496 treatment exhibited high cytotoxicity against human tumor cell lines with expression of BRAFV600E while had little effect on wild type BRAF expressed cell lines [2].
In nude mice model with Colo-205 tumor cells subcutaneous xenograft, oral administration of CEP-32496 significantly inhibited pMEK normalization, induced tumor stasis (40%) while control group did not have this phenomenon in a dose of 30 mg/kg [1].
CEP-32496 also inhibits MEK phosphorylation with IC 50 value of 60 nM [1].
References:
[1].James, J., et al., CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity. Mol Cancer Ther, 2012. 11(4): p. 930-41.
[2].Rowbottom, M.W., et al., Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropa n-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E. J Med Chem, 2012. 55(3): p. 1082-105.

Featured Products
New Products
 

References on CEP-32496 hydrochloride

Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropa n-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E.[Pubmed:22168626]

J Med Chem. 2012 Feb 9;55(3):1082-105.

The Ras/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway plays a central role in the regulation of cell growth, differentiation, and survival. Expression of mutant BRAF(V600E) results in constitutive activation of the MAPK pathway, which can lead to uncontrolled cellular growth. Herein, we describe an SAR optimization campaign around a series of quinazoline derived BRAF(V600E) inhibitors. In particular, the bioisosteric replacement of a metabolically sensitive tert-butyl group with fluorinated alkyl moieties is described. This effort led directly to the identification of a clinical candidate, compound 40 (CEP-32496). Compound 40 exhibits high potency against several BRAF(V600E)-dependent cell lines and selective cytotoxicity for tumor cell lines expressing mutant BRAF(V600E) versus those containing wild-type BRAF. Compound 40 also exhibits an excellent PK profile across multiple preclinical species. In addition, significant oral efficacy was observed in a 14-day BRAF(V600E)-dependent human Colo-205 tumor xenograft mouse model, upon dosing at 30 and 100 mg/kg BID.

Description

CEP-32496 Hcl is a highly potent inhibitor of BRAF(V600E/WT) and c-Raf with Kd of 14 nM/36 nM and 39 nM, also potent to Abl-1, c-Kit, Ret, PDGFRβ and VEGFR2, respectively; insignificant affinity for MEK-1, MEK-2, ERK-1 and ERK-2.

Keywords:

CEP-32496 hydrochloride,1227678-26-3,RXDX-105 hydrochloride; Agerafenib hydrochloride,Natural Products,Raf, buy CEP-32496 hydrochloride , CEP-32496 hydrochloride supplier , purchase CEP-32496 hydrochloride , CEP-32496 hydrochloride cost , CEP-32496 hydrochloride manufacturer , order CEP-32496 hydrochloride , high purity CEP-32496 hydrochloride

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: