1. MAPK/ERK Pathway
  2. Raf
  3. GNE-9815

GNE-9815 (compound 7) is a highly selective, pan-RAF inhibitor with good oral bioavailability. GNE-9815 exhibits Ki 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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GNE-9815 Chemical Structure

GNE-9815 Chemical Structure

CAS No. : 2729996-45-4

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
USD 242 In-stock
Solution
10 mM * 1 mL in DMSO USD 242 In-stock
Solid
5 mg USD 220 In-stock
10 mg USD 352 In-stock
25 mg USD 633 In-stock
50 mg USD 886 In-stock
100 mg USD 1240 In-stock
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Based on 1 publication(s) in Google Scholar

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Description

GNE-9815 (compound 7) is a highly selective, pan-RAF inhibitor with good oral bioavailability. GNE-9815 exhibits Ki 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[1].

IC50 & Target[1]

CRAF

0.062 nM (Ki)

Braf

0.19 nM (Ki)

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.

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 CLb, Vdss and t1/2 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).
Molecular Weight

455.48

Formula

C26H22FN5O2

CAS No.
Appearance

Solid

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.1955 mL 10.9774 mL 21.9549 mL
5 mM 0.4391 mL 2.1955 mL 4.3910 mL
View the Complete Stock Solution Preparation Table

* 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.

  • Molarity Calculator

  • Dilution Calculator

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

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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

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

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.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • 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.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 98.28%

References

Complete Stock Solution Preparation Table

* 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.

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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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Product Name:
GNE-9815
Cat. No.:
HY-142160
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