Agerafenib-CEP-32496-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAgerafenibCat. No.: HY-15200CAS No.: 1188910-76-0Synonyms: CEP-32496; RXDX-105分式: CHFNO分量: 517.46作靶点: Raf作通路: MAPK/ERK Pathway储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (96.63

2、 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.9325 mL 9.6626 mL 19.3252 mL5 mM 0.3865 mL 1.9325 mL 3.8650 mL10 mM 0.1933 mL 0.9663 mL 1.9325 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备

3、液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.83 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.83 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Mole

4、cules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (4.83 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Agerafenib (CEP-32496; RXDX-105)种服效的 BRAFV600E 抑制剂，Kd 为 14 nM。IC50 & Target Braf CRAF BRafV600E c-Kit36 nM (Kd) 39 nM (Kd) 14 nM (Kd) 2 nM (Kd)Ret LCK Abl-1 VEGFR-22 nM (Kd) 2 nM (Kd) 3 nM (Kd) 8 nM (Kd)CS

5、F-1R EPHA2 EGFR c-Met9 nM (Kd) 14 nM (Kd) 22 nM (Kd) 513 nM (Kd)JAK-2 MEK-1 MEK-24700 nM (Kd) 7100 nM (Kd) 8300 nM (Kd)体外研究 Agerafenib (CEP-32496) exhibits high potency against several BRAFV600E-dependent cell lines andselective cytotoxicity for tumor cell lines expressing mutant BRAFV600E versus th

6、ose containing wild-typeBRAF. Agerafenib exhibits potent binding (BRAFV600E Kd=14 nM) and cellular activity (pMEK IC50=82 nMand A375 proliferation IC50=78 nM), with activity in the proliferation assay. Agerafenib also exhibits afavorable CYP450 inhibition profile, with measured IC50 values greater t

7、han 10 M versus the CYP1A2,CYP2C9, CYP2D6, and CYP3A4 isoforms and an IC50=3.4 M versus CYP2C19 1.体内研究 Oral administration of Agerafenib (CEP-32496) to Colo-205 tumor xenograft-bearing mice results insignificant inhibition of pMEK in tumor cell lysates. For instance, a single 30 mg/kg (po) dose of A

8、gerafenibleads to a 50 and 75% inhibition of normalized pMEK in tumor lysates at the 2 and 6 h postdose time point,respectively (p 1.PROTOCOLCell Assay 1 A375 cells are seeded at 10,000 cells per well in DMEM with 10% fetal calf serum and allowed to attach. Thecells are washed with PBS and switched

9、to DMEM with 0.5% of serum and incubated overnight. The testcompounds (e.g., Agerafenib; 10 M) are then added at various concentrations with a final DMSOconcentration of 0.5% and incubated for 72 h. At the end of incubation, a Cell Titer Blue is added perinstructions, and incubation is continued for

10、 3 h. Remaining viable cells are quantified by measuring thestrength of the fluorescence signal using SoftMax Pro (excitation at 560 nm and emission at 590 nm). IC50values are derived using a 9-point curve and are presented as mean values from experiments performed induplicate 1.MCE has not independ

11、ently confirmed the accuracy of these methods. They are for reference only.Animal Mice 12/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAdministration 1 Six to eight week old athymic nu/nu nude mice (20-25 g) are inoculated subcutaneously with Colo-205 tumorcells (1106/mouse) in the right flank. Up

12、on reaching an average tumor volume of 150-200 mm3 (10-12 dayspost implantation), animals are randomized into treatment groups (n=10 mice/group). Each group is dosedorally for 14 days with either vehicle only (22% HPCD) or with Agerafenib at 10, 30, or 100 mg/kg twicedaily (BID), and each dose of dr

13、ug is given in a volume of 0.1 mL per 20 g of body weight, adjusted for thebody weight of the animal. Tumor volumes are measured three times weekly using vernier calipers, andvolumes are calculated 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品

14、发表的科研献 Science. 2017 Dec 1;358(6367). Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Nat Biomed Eng. 2018;2:578-588. Technical University of Munich. 24.01.2018.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. 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 homolo