Cobimetinib (GDC-0973, RG7420) is an effective, selective, oral MEK1 inhibitor with an IC50 of 4.2 nM against MEK1. In addition, Cobimetinib is an inhibitor of Akt.
Int J Mol Sci. 2018 Jan 18;19(1) pii: E289.
BRAF and MEK Inhibitors Influence the Function of Reprogrammed T Cells: Consequences for Adoptive T-Cell Therapy
Cobimetinib (GDC-0973) purchased from AbMole
 |
Source | Int J Mol Sci (2018). Figure 5. GDC-0973 (AbMole BioScience, Houston, TX, USA) |
| Method | vitro experiments | |
| Cell Lines | CAR-T cells | |
| Concentrations | 0.5 μM | |
| Incubation Time | 16 h | |
| Results | In contrast, the condition containing Cobi alone showed significantly reduced lytic capacity of the CAR-T cells, and this lytic capacity was even further reduced in the additional presence of Vem. |
 |
Source | Int J Mol Sci (2018). Figure 4. GDC-0973 (AbMole BioScience, Houston, TX, USA) |
| Method | vitro experiments | |
| Cell Lines | CAR-T cells | |
| Concentrations | 0.5 μM | |
| Incubation Time | 16 h | |
| Results | The presence of Vem alone, Tram alone,Cobi alone, Vem + Cobi, and Dabra + Tram, but not of Dabra alone seemed to reduce these quantities to approximately 50%. |
 |
Source | Int J Mol Sci (2018). Figure 3. GDC-0973 (AbMole BioScience, Houston, TX, USA) |
| Method | vitro experiments | |
| Cell Lines | CAR-T cells | |
| Concentrations | 0.5 μM | |
| Incubation Time | 16 h | |
| Results | Both MEKi significantly reduced IFN -secretion but the effect of Cobi alone was significantly stronger |
 |
Source | Int J Mol Sci (2018). Figure 2. GDC-0973 (AbMole BioScience, Houston, TX, USA) |
| Method | vitro experiments | |
| Cell Lines | CAR-T cells | |
| Concentrations | 0.5 μM | |
| Incubation Time | 16 h | |
| Results | Incubation with the MEK inhibitors Tram and Cobi alone, but also the combination of Vem + Cobi reduced the CD25 upregulation approximately to 50%. |
| Cell Experiment | |
|---|---|
| Cell lines | Human 888MEL (BRAFV600E) mutant melanoma cell lines |
| Preparation method | Plating cells in quadruplicate at a density of 3,000 per well in 384-well plates in normal growth medium and allowing to adhere overnight. Adding compounds in 10 concentrations based on a 3-fold dilution series. Using the CellTiter-Glo Luminescent Cell Viability Assay to measure cell viability 72 h later. |
| Concentrations | ~10 μM |
| Incubation time | 4 days |
| Animal Experiment | |
|---|---|
| Animal models | Human A375.X1 BRAFV600E mutant melanoma xenograft |
| Formulation | |
| Dosages | 5 mg/kg/day |
| Administration | orally daily (QD) for 2 1 consecutive days |
| Molecular Weight | 531.31 |
| Formula | C21H21F3IN3O2 |
| CAS Number | 934660-93-2 |
| Solubility (25°C) | DMSO 10 mM |
| 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.
| Related MEK Products |
|---|
| Glycinexylidide
Glycinexylidide (GX) is the active metabolite of Lidocaine. |
| Xantocillin
Xantocillin (Xanthocillin X) is a marine agent extracted from Penicillium commune, induces autophagy through inhibition of the MEK/ERK pathway. |
| MEK-IN-6 hydrate
MEK-IN-6 hydrate is a MEK inhibitor. |
| MS934
MS934 is a novel improved VHL-recruiting MEK 1/2 degrader. |
| Nedometinib
Nedometinib is a tyrosine kinase inhibitor targeting to MEK1. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
