Cobimetinib (Synonyms: GDC-0973, RG-7420, XL518) |
| رقم الكتالوجGC10033 |
A potent, orally available MEK1 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 934660-93-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Cobimetinib is a selective inhibitor of mitogen-activated protein kinase kinase (MEK) with IC50 value of 0.9 nM [1].
MEK is a kinase enzyme which selectively phosphorylates Ser/Thr and Tyr residues and involved in the mitogen-activated protein kinase (MAPK) signaling pathways that play an important role in regulation of cell proliferation, survival, differentiation, motility and angiogenesis [2].
In a KRAS G13D and B-RAF G464V mutant MDA-MB-231T breast adenocarcinoma cells, Cobimetinib inhibited MEK with IC50 value of 0.2 nM [1]. In pharmacokinetic-pharmacodynamic (PK-PD) model, Cobimetinib showed a sustained tumor pharmacodynamic response due to longer residence in tumor than in plasma [3].
In WM-266-4 xenograft mice, Cobimetinib decreased %pERK in tumor with IC50 values of 0.78 (WM-266-4) and 0.52 mM. Also, Cobimetinib (3.89 mM) increased IC50 value in WM-266-4 mice. In A375 xenograft mice, Cobimetinib (0.3-30 mg/kg) showed antitumor efficacy in a dose-dependent way. Cobimetinib is currently in phase I clinical trials as a potential antitumor agent [3].
References:
[1]. Rice KD, Aay N, Anand NK, et al. Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973). ACS Med Chem Lett, 2012, 3(5): 416-421.
[2]. Akinleye A, Furqan M, Mukhi N, et al. MEK and the inhibitors: from bench to bedside. J Hematol Oncol, 2013, 6: 27.
[3]. Wong H, Vernillet L, Peterson A, et al. Bridging the gap between preclinical and clinical studies using pharmacokinetic-pharmacodynamic modeling: an analysis of GDC-0973, a MEK inhibitor. Clin Cancer Res, 2012, 18(11): 3090-3099.
| Cell experiment [1]: | |
|
Cell lines |
KRAS G13D and B-RAF G464V mutant MDA-MB-231T breast adenocarcinoma cell lines |
|
Preparation method |
The solubility of this compound in DMSO is >26.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0-10 nM |
|
Applications |
In the biochemical activity c-Raf/MEK1/ERK study, cobimetinib inhibited MEK1 activity with a IC50 value of 0.9 nM. Additionally, in MDA-MB-231T breast adenocarcinoma cells with KRAS G13D and B-RAF G464V mutant, cobimetinib was found to be able to inhibit MEK with the IC50 value of 0.2 nM. |
| Animal experiment [1]: | |
|
Animal models |
MDA-MB-231T mouse xenograft model |
|
Dosage form |
0.3-30 mg/kg, oral, qd |
|
Application |
In an MDA-MB-231T efficacy study, cobimetinib demonstrated tumor growth inhibition values of 60 and 93% at 1 and 3 mg/kg, respectively, and statistically significant tumor regression was observed at higher doses. Overall, predicted ED50 and ED90 values were 0.6 and around 3 mg/kg/day, respectively, in the latter case corresponding to peak circulating plasma levels in the range of 130 nM. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] Rice KD, Aay N, Anand NK, et al. Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973). ACS Med Chem Lett, 2012, 3(5): 416-421. |
|
| Cas No. | 934660-93-2 | SDF | |
| المرادفات | GDC-0973, RG-7420, XL518 | ||
| Chemical Name | [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl]methanone | ||
| Canonical SMILES | C1CCNC(C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O | ||
| Formula | C21H21F3IN3O2 | M.Wt | 531.31 |
| الذوبان | ≥ 26.55 mg/mL in DMSO, ≥ 33.53 mg/mL in EtOH with gentle warming | Storage | Store at RT |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8821 mL | 9.4107 mL | 18.8214 mL |
| 5 mM | 0.3764 mL | 1.8821 mL | 3.7643 mL |
| 10 mM | 0.1882 mL | 0.9411 mL | 1.8821 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *