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Donafenib (Sorafenib D3)

Name: Donafenib (Sorafenib D3)
Brand: Selleck Chemicals
SKU: S9621

Synonyms: Bay 43-9006 D3, CM-4307

Catalog No.S9621 Purity: 99.93%

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

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

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Biological Activity

Description

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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
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

References

Chemical lnformation & 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	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years -20°C powder		1 month-20°Cin solvent

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

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In vivo
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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

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