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Bemcentinib (R428) Axl inhibitor

Name: Bemcentinib (R428)
SKU: S2841
Availability: InStock
Rating: 5 (132 reviews)

Cat.No.S2841

Bemcentinib (R428, BGB324) is an inhibitor of Axl with IC50 of 14 nM, demonstrating >100-fold selectivity for Axl over Abl. This compound is also more than 50- to 100-fold selective for Axl versus Mer and Tyro3, and exhibits 100-fold greater selectivity compared to InsR, EGFR, HER2, and PDGFRβ.

Chemical Structure

Molecular Weight: 506.64

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src FLT3 HER2 c-Kit Bcr-Abl MEK BTK IGF-1R ALK Trk receptor Syk CSF-1R c-RET FAK Mertk Tie-2 DYRK Tyro3 Ephrin receptor ROS1 Pyk2 RON DDR ACK Fer kinase
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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
A549 cells	Function assay		24 h	concomitant treatment of the cells with R428 and bafilomycin (Baf A1) or alleviated the vacuolization induced by R428.	30210917
Bel7404 cells	Function assay	1 μM	48 h	R428 altered the lysosomal pH and blocked autophagic degradation.	30210917
H1299	Growth inhibiton assay		48 h	R428 inhibited growth of H1299 in a dose-dependent manner with an IC50 of approximately 4 μM.	30210917
LM3 cells	Function assay	2.5 μM	0-36 h	R428 induced cytoplasmic vacuoles within one hour after R428 treatment, and the vacuoles increased in number and size with time.	30210917
HeLa cells	Function assay		1 h	Inhibition of recombinant AXL in human HeLa cells after 1 hr by ELISA, IC50=0.03 μM	26555154
KB-8-5-11	Function assay			P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen, Potency value= 14.581 μM	31515284
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	506.64	Formula	C₃₀H₃₄N₈	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1037624-75-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	BGB324			Smiles	C1CCN(C1)C2CCC3=C(CC2)C=C(C=C3)NC4=NN(C(=N4)N)C5=NN=C6C(=C5)CCCC7=CC=CC=C76

Solubility

In vitro
Batch:

DMSO : 25 mg/mL (49.34 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 20 mg/mL (39.47 mM) Warmed with 50°C water bath; Ultrasonicated;
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.600mg/ml (1.18mM)	Taking the 1 mL working solution as an example, add 50 μL of 12 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.000mg/ml (1.97mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	10% DMSO 1 40%PEG300 2 5%Tween80 3 45%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.500mg/ml (4.93mM)	Taking the 1 mL working solution as an example, add 100 μL of 25 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 450 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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.

Mechanism of Action

Targets/IC₅₀/Ki	Axl ^[1] (Cell-free assay) 14 nM
In vitro	Bemcentinib (R428) blocks the catalytic and procancerous activities of Axl. It inhibits Axl with low nanomolar activity and blocks Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. ^[1] In a recent study, this compound shows a mean IC50 dose of ∼ 2.0μM for the primary CLL B cells after 24 hours of treatment and normal B-, T-, and natural killer (NK) cells show no significant amount of cell death at this dose of R428 (2.5 μM) under similar experimental conditions. ^[2]
In vivo	Pharmacologic investigations reveal favorable exposure after oral administration of Bemcentinib (R428), such that treated tumors display a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. In support of an earlier study, it inhibits angiogenesis in corneal micropocket and tumor models. This compound also reduces metastatic burden and extends survival in MDA-MB-231 intracardiac and 4T1 orthotopic (median survival, >80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis. ^[1]
References	[1] https://pubmed.ncbi.nlm.nih.gov/20145120/ [2] https://pubmed.ncbi.nlm.nih.gov/21135257/

Applications

Methods	Biomarkers	PMID
Western blot	p-Axl (Y702) / Axl / Cleaved PARP caspase8 / caspase9 / Bcl-xl / Bcl-2	30210917
Growth inhibition assay	Cell viability	30210917
Immunofluorescence	LAMP1 / Lysosome E-cadherin / Vimentin / Axl	30210917

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03824080	Completed	Acute Myeloid Leukemia\|High-risk Myelodysplastic Syndrome\|Low-risk Myelodysplastic Syndrome	GWT-TUD GmbH\|Groupe Francophone des Myelodysplasies\|Amsterdam UMC location VUmc\|BerGenBio ASA	December 20 2018	Phase 2
NCT02922777	Completed	Non-Small Cell Lung Carcinoma	University of Texas Southwestern Medical Center\|Texas Tech University Health Sciences Center\|BerGenBio ASA	November 2016	Phase 1
NCT02424617	Completed	Non-Small Cell Lung Cancer	BerGenBio ASA	March 2015	Phase 1\|Phase 2
NCT02488408	Unknown status	Acute Myeloid Leukemia\|Myelodysplastic Syndromes	BerGenBio ASA	September 2014	Phase 1\|Phase 2

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

Question 1:
Could you please let me know whether this compound is an enantiomer or it is in its racemic form?

Answer:
Its e.e. value (enantiomeric purity) is >98%, and it is the S enantiomer.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):