Donafenib (Sorafenib D3)

Synonyms: Bay 43-9006 D3, CM-4307

Donafenib (Sorafenib D3, Bay 43-9006 D3, CM-4307) is the deuterium labeled Sorafenib. Sorafenib is a multikinase inhibitor IC50s of 6 nM, 15 nM, 20 nM and 22 nM for Raf-1, mVEGFR-2, mVEGFR-3 and B-RAF, respectively.

Donafenib (Sorafenib D3) Chemical Structure

Donafenib (Sorafenib D3) Chemical Structure

CAS: 1130115-44-4

Purity & Quality Control

Batch: S962101 DMSO] 94 mg/mL] false] Ethanol] 6 mg/mL] false] Water] Insoluble] false Purity: 99.93%
99.93

Donafenib (Sorafenib D3) Related Products

Signaling Pathway

Choose Selective Raf Inhibitors

Biological Activity

Description Donafenib (Sorafenib D3, Bay 43-9006 D3, CM-4307) is the deuterium labeled Sorafenib. Sorafenib is a multikinase inhibitor IC50s of 6 nM, 15 nM, 20 nM and 22 nM for Raf-1, mVEGFR-2, mVEGFR-3 and B-RAF, respectively.
Targets
Raf-1 [1]
(Cell-free assay)
mVEGFR-2 [1]
(Cell-free assay)
mVEGFR-3 [1]
(Cell-free assay)
B-Raf [1]
(Cell-free assay)
6 nM 15 nM 20 nM 22 nM
In vitro
In vitro

BAY 43-9006 suppresses both wild-type and V599E mutant BRAF activity in vitro. In addition, BAY 43-9006 demonstrates significant activity against several receptor tyrosine kinases involved in neovascularization and tumor progression, including vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor β, Flt-3, and c-KIT. In cellular mechanistic assays, BAY 43-9006 demonstrates inhibition of the mitogen-activated protein kinase pathway in colon, pancreatic, and breast tumor cell lines expressing mutant KRAS or wild-type or mutant BRAF, whereas non–small-cell lung cancer cell lines expressing mutant KRAS are insensitive to inhibition of the mitogen-activated protein kinase pathway by BAY 43-9006. Potent inhibition of VEGFR-2, platelet-derived growth factor receptor β, and VEGFR-3 cellular receptor autophosphorylation is also observed for BAY 43-9006.[1]

Cell Research Cell lines MDA-MB-231, Colo-205, HT-29, DLD-1, NCI-H460, A549 cell lines
Concentrations 0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM
Incubation Time 120 min
Method

Tumor cell lines are plated at 2 × 105 cells per well in 12-well tissue culture plates in DMEM growth media (10% heat-inactivated FCS) overnight. Cells are washed once with serum-free media and incubated in DMEM supplemented with 0.1% fatty acid-free BSA containing various concentrations of Donafenib (Sorafenib D3, BAY 43-9006) in 0.1% DMSO for 120 minutes to measure changes in basal pMEK 1/2, pERK 1/2, or pPKB. Cells are washed with cold PBS (PBS containing 0.1 mmol/L vanadate) and lysed in a 1% (v/v) Triton X-100 solution containing protease inhibitors. Lysates are clarified by centrifugation, subjected to SDS-PAGE, transferred to nitrocellulose membranes, blocked in TBS-BSA, and probed with anti-pMEK 1/2 (Ser217/Ser221; 1:1000), anti-MEK 1/2, anti-pERK 1/2 (Thr202/Tyr204; 1:1000), anti-ERK 1/2, anti-pPKB (Ser473; 1:1000), or anti-PKB primary antibodies. Blots are developed with horseradish peroxidase (HRP)-conjugated secondary antibodies and developed with Amersham ECL reagent on Amersham Hyperfilm.

In Vivo
In vivo

Once daily oral dosing of BAY 43-9006 demonstrates broad-spectrum antitumor activity in colon, breast, and non–small-cell lung cancer xenograft models. Immunohistochemistry demonstrates a close association between inhibition of tumor growth and inhibition of the extracellular signal-regulated kinases (ERKs) 1/2 phosphorylation in two of three xenograft models examined, consistent with inhibition of the RAF/MEK/ERK pathway in some but not all models. Additional analyses of microvessel density and microvessel area in the same tumor sections using antimurine CD31 antibodies demonstrates significant inhibition of neovascularization in all three of the xenograft models.[1]

Animal Research Animal Models Female NCr-nu/nu mice
Dosages 7.5 mg/kg, 15 mg/kg, 30 mg/kg, 60 mg/kg
Administration Oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04612712 Recruiting
Advanced Gastrointestinal Tumors
Suzhou Zelgen Biopharmaceuticals Co.Ltd|Jiangsu Alphamab Biopharmaceuticals Co. Ltd
January 19 2021 Phase 1|Phase 2
NCT04816123 Completed
Healthy Male Adult
Suzhou Zelgen Biopharmaceuticals Co.Ltd
October 9 2018 Phase 1

Chemical Information & Solubility

Molecular Weight 467.84 Formula

C21H13D3ClF3N4O3

CAS No. 1130115-44-4 SDF --
Smiles CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 94 mg/mL ( (200.92 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 6 mg/mL

Water : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg 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.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

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.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Donafenib (Sorafenib D3) | Donafenib (Sorafenib D3) supplier | purchase Donafenib (Sorafenib D3) | Donafenib (Sorafenib D3) cost | Donafenib (Sorafenib D3) manufacturer | order Donafenib (Sorafenib D3) | Donafenib (Sorafenib D3) distributor