Art. -Nr.: HY-142160

GNE-9815

Name: GNE-9815
Brand: MedChemExpress
SKU: HY-142160
Price: 220.00 USD
Availability: InStock
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GNE-9815 (compound 7) is a highly selective, pan-RAF inhibitor with good oral bioavailability. GNE-9815 exhibits K_i values of 0.062 and 0.19 nM for CRAF and BRAF, respectively. GNE-9815 combines with MEK inhibitor Cobimetinib (HY-13064) shows synergistic modulation of MAPK pathway. GNE-9815 can be used in studies of KRAS mutant cancers.

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Reinheit : 98.94%
CAS. Nr.: 2729996-45-4
Formel: C₂₆H₂₂FN₅O₂
Molecular Weight:455.48

Speicherung:

Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month

GNE-9815 Chemical Structure

CAS. Nr.: 2729996-45-4

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll (1)
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

^[1]

CRAF

0.062 nM (Ki)

Braf

0.19 nM (Ki)

Alle Raf Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	369 nM Compound: 7; GNE-9815	Synergistic antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability in presence of 100 nM cobi-metinib Synergistic antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability in presence of 100 nM cobi-metinib	[PMID: 34055227]
A549	IC₅₀	5470 nM Compound: 7; GNE-9815	Antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability Antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability	[PMID: 34055227]

In Vitro

GNE-9815 shows synergistic activity in KRAS mutant A549 and HCT116 cancer cells in combination with the MEK inhibitor Cobimetinib^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.

In Vivo

GNE-9815 (15 mg/kg; p.o.; single) demonstrates synergistic MAPK pathway modulation when combines with the MEK inhibitor Cobimetinib in an HCT116 xenograft mouse model^[1].
GNE-9815 (5 mg/kg; p.o.; single) shows good oral bioavailability and (1 mg/kg; i.v.; single) exhibits low blood clearance, moderate volume of distribution, and short half-life^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Female NCR nude mice (6 to 8-week-old; 24-26 g; HCT116 xenograft mice model)^[1].
Dosage:

15 mg/kg
Administration:

Intravenous injection or oral administration; single.
Result:

Resulted in pathway inhibition as demonstrated by partial inhibition of pRSK between 2 and 24 h, but more robust, albeit transient, inhibition of the downstream MAPK target genes, DUSP6 and SPRY4.
Led to deeper inhibition of the downstream MAPK target genes DUSP6 and SPRY4, when combined with the MEK inhibitor Cobimetinib, with maximal inhibition at 8 h and with a more modest rebound in levels at 24 h, post final dose.

Animal Model:

Female NCR nude mice (6 to 8-week-old; 24-26 g)^[1].
Dosage:

1 mg/kg (for i.v.); 5 mg/kg (for p.o.).
Administration:

Intravenous injection or oral administration; single.
Result:

Exhibited CL_b, V_dss and t_1/2 values of 17 mL/min∙kg, 1.7 L/kg and 1.9 h, respectively.
Showed good oral bioavailability with F% of 37%. (methylcellulose/Tween formulation).

Chemical Information

CAS. Nr. 2729996-45-4
Appearance Solid
Molecular Weight 455.48
Formel C₂₆H₂₂FN₅O₂
Color Off-white to light yellow
SMILES

N#CC(C)(C)C1=CC(C(NC2=C(F)C=C(C)C(C3=CN=C4C(C=NN(C)C4=O)=C3)=C2)=O)=CC=C1
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 50 mg/mL (109.77 mM; ultrasonic and warming and heat to 80°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.1955 mL

10.9774 mL

21.9549 mL

5 mM

0.4391 mL

2.1955 mL

4.3910 mL

10 mM

0.2195 mL

1.0977 mL

2.1955 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (5.49 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (5.49 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (5.49 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protokoll

All Animals and Diseases

Protocol for Pharmacokinetic Study
Pharmacokinetic studies quantify how an organism handles a drug over time through absorption, distribution, metabolism, and excretion, and the core experimental readout is the concentration-time profile of parent drug and, when relevant, metabolites in biological matrices such as plasma, whole blood, urine, bile, or tissue. Pharmacokinetic analysis links dose, route, exposure, clearance, half-life, distribution, bioavailability, and systemic exposure to drug efficacy and toxicity hypotheses rather than measuring a signaling pathway directly. The literature links pharmacokinetics to drug-development phenotypes by showing that drug metabolism and pharmacokinetics influence compound progression, exposure-response interpretation, safety margins, dosing strategy, and failure risk during discovery and development. DMPK science contributes to compound optimization by integrating physicochemical properties, in vitro metabolism, transporter behavior, in vivo exposure, and pharmacodynamic contex

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (272 KB)
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Huestis MP, et al. Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a Pyridopyridazinone pan-RAF Kinase Inhibitor. ACS Med Chem Lett. 2021 Apr 21;12(5):791-797. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.1955 mL	10.9774 mL	21.9549 mL	54.8872 mL
	5 mM	0.4391 mL	2.1955 mL	4.3910 mL	10.9774 mL
	10 mM	0.2195 mL	1.0977 mL	2.1955 mL	5.4887 mL
	15 mM	0.1464 mL	0.7318 mL	1.4637 mL	3.6591 mL
	20 mM	0.1098 mL	0.5489 mL	1.0977 mL	2.7444 mL
	25 mM	0.0878 mL	0.4391 mL	0.8782 mL	2.1955 mL
	30 mM	0.0732 mL	0.3659 mL	0.7318 mL	1.8296 mL
	40 mM	0.0549 mL	0.2744 mL	0.5489 mL	1.3722 mL
	50 mM	0.0439 mL	0.2195 mL	0.4391 mL	1.0977 mL
	60 mM	0.0366 mL	0.1830 mL	0.3659 mL	0.9148 mL
	80 mM	0.0274 mL	0.1372 mL	0.2744 mL	0.6861 mL
	100 mM	0.0220 mL	0.1098 mL	0.2195 mL	0.5489 mL

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GNE-9815

Alle Raf Isoform-spezifische Produkte anzeigen